Novel BRCA1 and BRCA2 germline mutations and assessment of mutation spectrum and prevalence in Italian breast and/or ovarian cancer families

Abstract  Familial aggregations of breast/ovarian cancer cases frequently depend on BRCA1/2 pathogenic mutations. Here we counselled 120 Italian breast/ovarian cancer families and selected 73 probands for BRCA1/2 mutation screening. Through this analysis we defined the prevalence of BRCA1/2 pathogenic mutations occurring in Italian breast/ovarian cancer families, enlarged the spectrum of Italian BRCA1/2 mutations by 15% and report on the identification of 13 novel variants, including two deleterious truncating mutations and two potentially pathogenic missense mutations, on the BRCA1 and BRCA2 genes. Finally in hereditary breast cancer families with three or more female breast cancer cases we observed a low mutation prevalence and a significant association with BRCA2 mutations.

Infertility, Ovulation Induction Treatments and the Incidence of Breast Cancer—a Historical Prospective Cohort of Israeli Women

AbstractContext  Ovulation induction drugs may be associated with increased breast cancer risk. Results so far have been inconclusive.

Performance profile of FDG-PET and PET/CT for cancer screening on the basis of a Japanese Nationwide Survey

Abstract Objective  The aim of this study is to survey the situation of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) cancer screening in Japan and to describe its performance profile.

Flexible heteroarotinoids (Flex-Hets) exhibit improved therapeutic ratios as anti-cancer agents over retinoic acid receptor agonists

Abstract  The anti-cancer activities and toxicities of retinoic acid (RA) and synthetic retinoids are mediated through nuclear RA receptors (RARs) and retinoid X receptors (RXRs) that act as transcription factors. Heteroarotinoids (Hets), which contain a heteroatom in the cyclic ring of an arotinoid structure, exhibit similar anti-cancer activities, but reduced toxicity in vivo, in comparison to parent retinoids and RA. A new class of Flexible Hets (Flex-Hets), which contain 3-atom urea or thiourea linkers, regulate growth and differentiation similar to RA, but do not activate RARs or RXRs. In addition, Flex-Hets induce potent apoptosis in ovarian cancer and in head and neck cancer cell lines through the intrinsic mitochondrial pathway. In this study, 4 cervical cancer cell lines were growth inhibited by micromolar concentrations of Flex-Hets to greater extents than RAR/RXR active retinoids. The most potent Flex-Het (SHetA2) inhibited each cell line of the National Cancer Institute’s human tumor cell line panel at micromolar concentrations. Oral administration of Flex-Hets (SHetA2 and SHetA4) inhibited growth of OVCAR-3 ovarian cancer xenografts to similar extents as administration of a RAR/RXR-panagonist (SHet50) and Fenretinide (4-HPR) in vivo. None of these compounds induced evidence of skin, bone or liver toxicity, or increased levels of serum alanine aminotransferase (ALT) in the treated mice. Topical application of Flex-Hets did not induce skin irritation in vivo, whereas a RAR/RXR-panagonist (NHet17) and a RARγ-selective agonist (SHet65) induced similar irritancy as RA. In conclusion, Flex-Hets exhibit improved therapeutic ratios for multiple cancer types over RAR and/or RXR agonists.

Pre-clinical Study of 213Bi Labeled PAI2 for the Control of Micrometastatic Pancreatic Cancer

Abstract  Purpose: The urokinase plasminogen activator (uPA) and its receptor (uPAR) are expressed by pancreatic cancer cells and can be targeted by the plasminogen activator inhibitor type 2 (PAI2). We have labeled PAI2 with 213Bi to form the alpha conjugate (AC), and have studied its in vitro cytotoxicity and in vivo efficacy. Methods and Materials: The expression of uPA/uPAR on pancreatic cell lines, human pancreatic cancer tissues, lymph node metastases, and mouse xenografts were detected by immunohistochemistry, confocal microscopy, and flow cytometry. Cytotoxicity was assessed by the MTS and TUNEL assay. At 2 days post-cancer cell subcutaneous inoculation, mice were injected with AC by local or systemic injection.

Increased expression of CEA and MHC class I in colorectal cancer cell lines exposed to chemotherapy drugs

AbstractPurpose  Cancer-specific immunotherapy holds great promise as an emerging treatment for advanced colorectal cancer and may be combined with standard chemotherapy to provide a synergistic inhibitory action against tumor cells. To examine the interrelationship between the immune system and chemotherapy, we studied the induction of both CEA, a tumor-associated antigen, and MHC class I, a major component of the antigen presenting system, in response to a number of chemotherapeutic agents.

Axillary Recurrence After Negative Sentinel Node Biopsy in a Patient with Breast Cancer: Report of a Case

Abstract  We report a case of axillary recurrence after sentinel node biopsy without axillary lymph node dissection in a patient with breast cancer. A hot and dye-stained node was identified at the primary operation and then at the time of axillary recurrence. Sentinel node biopsy is a promising alternative to axillary lymph node dissection in patients with breast cancer because of the low associated incidence of axillary recurrence.

Flame-broiled food, NAT2acetylator phenotype, and breast cancer risk among women with benign breast disease

AbstractPurpose  The objective of this study was to examine the association between flame-broiled food consumption, a source of heterocyclic amine exposure, and the development of breast cancer among cohort of women with benign breast disease (BBD). The variation of the association by acetylation phenotype, as determined by the genotypes of selected N-acetyltransferase 2 (NAT2) enzymes, was also examined.

Physical activity, long-term symptoms, and physical health-related quality of life among breast cancer survivors: A prospective analysis

Abstract Introduction  Many breast cancer survivors experience persistent physical symptoms of cancer and treatment that can decrease health-related quality of life (HRQOL). This prospective study investigated physical activity (PA), occurrence of physical symptoms, and HRQOL in a large, ethnically-diverse cohort of breast cancer survivors.

Short term correlates of the Neuro Emotional Technique for cancer-related traumatic stress symptoms: A pilot case series

Abstract Introduction  As many as one quarter of all cancer survivors report traumatic stress symptoms from cancer-related experiences. While the majority of these patients do not meet the criteria for posttraumatic stress disorder (PTSD), there is growing evidence that subsyndromal symptoms can significantly contribute to functional impairment and negative health outcomes. Treatment options for the hallmark symptoms of traumatic stress—unpleasant, intrusive thoughts and avoidant behaviors—have not been well investigated for the cancer survivorship population.

Evaluation of an inflammation-based prognostic score (GPS) in patients undergoing resection for colon and rectal cancer

Abstract Background/aims  The aim of the study was to examine the value of the combination of an elevated C-reactive protein and hypoalbuminaemia (GPS) in predicting cancer-specific survival after resection for colon and rectal cancer.

Family History, and Impact on Clinical Presentation and Prognosis, in a Population-based Breast Cancer Cohort from the Stockholm County

AbstractBackground  The aim of the present study was to define the proportion of different levels of family history in a cohort of consecutive breast cancer patients from the Stockholm region, and to assess whether familial breast cancer has phenotypic traits different from those of sporadic patients.

Surgical Strategy for Advanced Gastric Cancer with a Concomitant Thoracoabdominal Aortic Aneurysm Requiring Arterial Reconstruction of the Visceral Branches

Abstract  A 70-year-old man who presented with hematemesis was found to have advanced gastric cancer concomitant with a thoracoabdominal aortic aneurysm (TAAA), which involved all branches of the visceral arteries. The patient underwent the following staged operations: first, radical resection of the advanced gastric cancer with simultaneous reconstruction of the visceral branches, followed 1 month later by endovascular aortic replacement of the TAAA. He recovered uneventfully and was discharged without any paralytic complications or sign of graft infection.

Protein and mRNA expression of tissue factor pathway inhibitor-1 (TFPI-1) in breast, pancreatic and colorectal cancer cells

Abstract Background  Patients with solo tumour malignancy are at higher risk of developing venous thromboembolism. When prophylactic anticoagulation (and in particular heparin) is used during cancer therapy however, patients appear to have a prolonged survival. Tumours express large quantities of procoagulant molecules, which predispose patients to these conditions. Tissue Factor (TF) is an important example, which may have a role in the biology of malignant disease. Intra-tumour vessel coagulation however is not a common phenomenon. Our hypothesis is that cancer cells produce anticoagulant molecules, which may prevent intra-tumour vessel auto-coagulation. Our results show that one such factor—Tissue Factor Pathway Inhibitor (TFPI-1) is expressed by a number of different cancer cells.

Methylenetetrahydrofolate reductase (MTHFR) and breast cancer risk: a nested-case-control study and a pooled meta-analysis

Abstract Background  A reduced activity of methylenetetrahydrofolate reductase (MTHFR) due to frequent C677T polymorphism affects DNA synthesis, repair and methylation and may be implicated in breast cancer risk.

Missed Opportunities: Family History and Behavioral Risk Factors in Breast Cancer Risk Assessment Among a Multiethnic Group of Women

Background  Clinician’s knowledge of a woman’s cancer family history (CFH) and counseling about health-related behaviors (HRB) is necessary for appropriate breast cancer care.

Concentration-dependent effects of genistein on global gene expression in MCF-7 breast cancer cells: an oligo microarray study

Abstract  Breast cancer is the most commonly diagnosed cancer among US women; there is therefore great interest in developing preventive and treatment strategies for this disease. Because breast cancer incidence is much lower in countries where women consume high levels of soy, bioactive compounds in this food source have been studied for their effects on breast cancer. Genistein, found at high levels in soybeans and soy foods, is a controversial candidate breast cancer preventive phytochemical whose effects on breast cells are complex. To understand more clearly the molecular mechanisms underlying the effects of genistein on breast cancer cells, we used a DNA oligo microarray approach to examine the global gene expression patterns in MCF-7 breast cancer cells at both physiologic (1 or 5 μM) and pharmacologic (25 μM) genistein concentrations. Microarray analyses were performed on MCF-7 cells after 48 h of either vehicle or 1, 5, or 25 μM genistein treatment. We found that genistein altered the expression of genes belonging to a wide range of pathways, including estrogen- and p53-mediated pathways. At 1 and 5 μM, genistein elicited an expression pattern suggestive of increased mitogenic activity, confirming the proliferative response to genistein observed in cultured MCF-7 cells, while at 25 μM genistein effected a pattern that likely contributes to increased apoptosis, decreased proliferation and decreased total cell number, also consistent with cell culture results. These findings provide evidence for a molecular signature of genistein’s effects in MCF-7 cells and lay the foundation for elucidating the mechanisms of genistein’s biological impact in breast cancer cells.

Expression of estrogen receptor-related receptors, a subfamily of orphan nuclear receptors, as new tumor biomarkers in ovarian cancer cells

Abstract  A subfamily of orphan receptors, estrogen receptor-related receptors (ERRs), has been demonstrated to modulate the transcription of some estrogen responsive genes via variant estrogen response elements (EREs). This study was conducted to determine whether human ERR, ERR, and ERR might be involved in the tumorigenesis of ovarian cancer. RT-PCR was performed to analyze the expression of hERR, hERR, hERR-2, and hERR mRNA in five ovarian cancer cell lines as well as 33 samples of ovarian cancer and 12 samples of normal ovary. Serum CA-125 levels were also analyzed in all samples by ELISA. Progression-free survival and overall survival of patients with different expression of ERRs were analyzed by the Kaplan–Meier method. To analyze the subcellular localization of ERR, a green fluorescent protein (GFP)-reporter plasmid of hERR was constructed and transfected into the ovarian cancer cell line OVCAR-3. Expression of hERR-GFP fusion protein was observed in the nucleus of OVCAR-3 ovarian cancer cell lines. We observed increased expression of hERR mRNA (P=0.020) and hERR mRNA (P=0.045) in ovarian cancers compared to normal ovaries. In contrast, hERR was only observed in 9.1% of ovarian cancers. We found a positive correlation between the serum CA-125 levels and hERR expression (P=0.012), but not hERR and hERR expression. Survival analysis showed that the hERR-positive group has a reduced overall survival (P=0.015), and the ERR-positive group has a longer progression-free survival (P=0.020). In multivariate analysis, expression of hERR was an independent prognostic factor for poor survival (relative risk, 3.032; 95% CI, 1.27–6.06). Based on our results, ERRs may play an important role in ovarian cancer. hERR may represent a biomarker of poor prognosis, and hERR may be a new therapeutic target in ovarian cancer.

Detection of K- ras mutations in the plasma DNA of pancreatic cancer patients

Background  In pancreatic cancers, K-ras mutations have been found frequently (80%–100%), and they could be a good marker to detect tumor DNA in the plasma. Several studies have indicated that polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) analysis of K-ras mutation was a useful method for the detection of hepatic and lymph node metastasis of pancreatic cancer. However, this method sometimes exhibited false-positive results, and the rate of K-ras mutation might thus be overestimated in these tissues. To diagnose pancreatic cancer correctly at an early stage, we attempted to detect tumor DNA in the plasma of pancreatic cancer patients using a more sensitive and specific method.Methods  We examined 28 pancreatic cancer patients using a sensitive mutation-specific mismatch ligation assay for K-ras gene mutations in primary tumors and paired plasma samples.

Consumption of different types of meat and the risk of renal cancer: meta-analysis of case–control studies

Abstract Background  Kidney cancers account for almost 2% of all cancers worldwide, with 150,000 new cases and 78,000 deaths from the disease occurring annually. An increase in the incidence of kidney neoplasm in western countries was noticed in the past few years. Between 1988 and 1992, the incidence of renal cancer per 100,000 person-year among males in USA, Norway, and France was 34.1, 9.00, and 16.10, respectively. Among females in the same countries, it was 5.70, 5.00, and 7.30, respectively. Although several individual case–control studies examined the association of meat intake and renal cancer risk, the results were inconsistent because of the insufficient statistical power of the individual studies. Therefore, the following meta-analysis was designed to help in clarifying the association.

The 471delAAAG Mutation and C353T Polymorphism in the RNASEL Gene in Sporadic and Inherited Cancer in Israel

Abstract  The rate of RNASEL 471delAAAG mutation was previously reported to be less than 7% in Ashkenazi prostate cancer patients. It seems plausible that the same mutation may also be involved in breast/ovarian cancer predisposition in Jewish individuals. To evaluate the role of this mutation in cancer predisposition, a total of 1011 individuals including 294 Jewish men with prostate cancer, 61 Ashkenazi women with ovarian cancer and 50 unaffected women, matched for age and ethnicity, were genotyped for sequence anomalies in a single RNASEL gene amplicon using DGGE and sequencing. Additionally, 209 Ashkenazi BRCA1/2 mutation carriers, 205 high-risk non-carriers matched for cancer type and age at diagnosis, and 192 healthy Ashkenazi women were screened, using DHPLC and restriction methods. The 471delAAAG mutation was detected in a single male with prostate cancer (1/294, 0.3%), in two ovarian cancer patients (2/141, 1.4%) and in one of 242 healthy controls (0.41%). An abnormal DHPLC profile identical to the one produced by the 471delAAAG mutation was noted in 23 additional women. The rate of this polymorphism was significantly elevated in high-risk non-carrier women (16/205; 7.8%) than in BRCA1/2 carriers (2/209; 1.0%) and controls (5/192; 2.6%) (χ = 11.670; P < 0.001). Sequence analysis disclosed a silent polymorphism in Valine at codon 118: c.353 C- > T.The 471delAAAG mutation occurs rarely in Israeli prostate and breast/ovarian cancer patients. A silent polymorphism in the RNASEL gene occurs more␣prevalently in high-risk Ashkenazi breast/ovarian cancer patients without a BRCA1/2 mutation.

Sodium/potasium ATPase (Na+, K+-ATPase) and ouabain/related cardiacglycosides: a new paradigm for development of anti- breast cancer drugs?

Summary  Prolonged exposure to 17β-estradiol (E2) is a key etiological factor for human breast cancer. The biological effects and carcinogenic effects of E2 are mediated via estrogen receptors (ERs), ERα and ERβ. Anti-estrogens, e.g. tamoxifen, and aromatase inhibitors have been used to treat ER-positive breast cancer. While anti-estrogen therapy is initially successful, a major problem is that most tumors develop resistance and the disease ultimately progresses, pointing to the need of developing alternative drugs targeting to other critical targets in breast cancer cells. We have identified that Na+, K+-ATPase, a plasma membrane ion pump, has unique/valuable properties that could be used as a potentially important target for breast cancer treatment: (a) it is a key player of cell adhesion and is involved in cancer progression; (b) it serves as a versatile signal transducer and is a target for a number of hormones including estrogens and (d) its aberrant expression and activity are implicated in the development and progression of breast cancer. There are several lines of evidence indicating that ouabain and related digitalis (the potent inhibitors of Na+, K+-ATPase) possess potent anti-breast cancer activity. While it is not clear how the suggested anti-cancer activity of these drugs work, several observations point to ouabain and digitalis as being potential ER antagonists. We critically reviewed many lines of evidence and postulated a novel concept that Na+, K+-ATPase in combination with ERs could be important targets of anti-breast cancer drugs. Modulators, e.g. ouabain and related digitalis could be useful to develop valuable anti-breast cancer drugs as both Na+, K+-ATPase inhibitors and ER antagonists.

évaluation par l’imagerie des traitements néo–adjuvants des cancers du sein

Résumé:   Le rôle de limagerie chezles patientes traitées par des thérapiesnéo–adjuvantes pour un cancerdu sein nest pas seulement dévaluerla diminution de la massetumorale, mais aussi de prédire laréponse histologique à la chimiothérapie,facteur corrélé à la survie.Lintervention chirurgicale etlanalyse anatomo–pathologiqueaprès le traitement néo–adjuvantpermettent de contrôler objectivementla fiabilité des modalitésdimagerie pour lévaluation de laréponse. Le but de cette étude estde comparer lintérêt des différentestechniques dimagerie morphologiqueset fonctionnelles dansla détermination de la réponse autraitement néo–adjuvant du cancerdu sein.

Attenuation of Estrogen Receptor α (ERα) Signaling by Selenium in Breast Cancer Cells via Downregulation of ERα Gene Expression

Summary  Numerous studies have shown that selenium provides beneficial effects as a cancer chemoprevention agent. Although long-term intervention trials failed to confirm selenium protection against breast cancer in humans because of insufficient cases, the evidence of effective selenium chemoprevention in animal mammary tumor models or human breast cancer cells is substantial and convincing. The present study demonstrates that the selenium compound methylseleninic acid (MSA) inhibits estrogen receptor α (ERα) signaling in ER-positive MCF-7 breast cancer cells as evidenced by decreased estradiol-dependent cell growth and gene expression. MSA diminishes estradiol induction of endogenous ER-regulated pS2 and c-myc genes as well as the expression of an ER-regulated reporter gene. A major mode of MSA action on ER signaling is through a downregulation of ERα gene expression that precedes a decrease in ERα protein level. This study provides a mechanism driven rationale for using selenium as a chemopreventive agent for women at high risk for developing breast cancer or as a therapeutic strategy for ER-positive breast cancer.

Early life events and later risk of colorectal cancer: age-period-cohort modelling in the Nordic countries and Estonia

Abstract.  Background: A lowering of colorectal cancer risk for the birth cohorts born around World War II (WWII) has previously been observed in Norway, a country which suffered some 20% caloric restriction during the war. The purpose of the study was to conduct a similar kind of analysis in the other Nordic countries and Estonia, which were also subjected to various degrees of energy restriction during WWII.Methods: All new cases of colorectal cancer in the Nordic countries and Estonia diagnosed between 40 and 84 years of age and born between 1874 and 1953, were collected from the national cancer registries. The incidence data were fitted to an age-period-cohort model.

Previous oral contraceptive use and breast cancer risk according to hormone replacement therapy use among postmenopausal women

AbstractObjective  To assess postmenopausal breast cancer risk in relation to particular patterns of oral contraceptive (OC) use according to hormone replacement therapy (HRT) exposure.

KiSS1 Suppresses Metastasis in Human Ovarian Cancer via Inhibition of Protein Kinase C Alpha

Abstract  Metastasis is a vital target for cancer treatment, since the majority of cancer patients die from metastatic, rather than the primary disease. KiSS1 has been identified as a metastasis suppressor gene in melanoma and breast carcinomas. We show here that KiSS1 is also a metastasis suppressor in human ovarian cancer. Overexpression of KiSS1 in ovarian cancer cells inhibits cell migration induced by serum or lysophosphatidic acid (LPA), and colonization in soft agar, but not cell proliferation, representing the characteristics of a metastasis suppressor gene. Furthermore, using an experimental metastatic mouse model, we show that expression of KiSS1 in SKOV3 ovarian cancer cells suppresses >50% metastatic colonization in mice (P < 0.0001). We find that activating protein kinase C (PKC) reverses about 80% of the inhibited cell migration induced by KiSS1, while down-regulation of PKCα with shRNA restores KiSS1 effect, providing evidence that inhibiting PKCα may be an important mechanism of the effect of KiSS1. These results suggest that KiSS1 is a metastasis suppressor of ovarian cancer and may be a potential molecular target for the treatment.

Race/Ethnicity and Changing US Socioeconomic Gradients in Breast Cancer Incidence: California and Massachusetts, 1978–2002 (United States)

Abstract  Objective We tested the hypothesis that the US socioeconomic gradient in breast cancer incidence is declining, with the decline most pronounced among racial/ethnic groups with the highest incidence rates. Methods We geocoded the invasive incident breast cancer cases for three US population-based cancer registries covering: Los Angeles County, CA (1978–1982, 1988–1992, 1998–2002; n = 68,762 cases), the San Francisco Bay Area, CA (1978–1982, 1988–1992, 1998–2002; n = 37,210 cases) and Massachusetts (1988–1992, 1998–2002; n = 48,111 cases), linked the records to census tract area-based socioeconomic measures, and, for each socioeconomic stratum, computed average annual breast cancer incidence rates for the 5-year period straddling the 1980, 1990, and 2000 census, overall and by race/ethnicity and gender.

COX-2 Polymorphism, Use of Nonsteroidal Anti-Inflammatory Drugs, and Risk of Colon Cancer in African Americans (United States)

Abstract Introduction   The inducible Cyclooxygenase (COX)-2 enzyme plays an important role in inflammation and carcinogenesis. Recent reports suggest that single nucleotide polymorphisms (SNPs) in the COX-2 gene may alter enzyme function and in turn modify an individual’s risk of colon cancer. We explored the association between the COX-2 Val511Ala SNP and risk of colon cancer among 240 African American cases and 326 African American controls in a population-based, case-control study in North Carolina.

A Pooled Analysis of 12 Cohort Studies of Dietary Fat, Cholesterol and Egg Intake and Ovarian Cancer

Abstract  Fat and cholesterol are theorized to promote ovarian carcinogenesis by increasing circulating estrogen levels. Although case–control studies have reported positive associations between total and saturated fat intake and ovarian cancer risk, two cohort studies have observed null associations. Dietary cholesterol and eggs have been positively associated with ovarian cancer risk. A pooled analysis was conducted on 12 cohort studies. Among 523,217 women, 2,132 incident epithelial ovarian cancer cases were identified. Study-specific relative risks (RR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards models, and then pooled using a random effects model. Total fat intake was not associated with ovarian cancer risk (pooled multivariate RR = 1.08, 95% CI 0.86–1.34 comparing ≥45 to 30–<35% of calories). No association was observed for monounsaturated, polyunsaturated, trans-unsaturated, animal and vegetable fat, cholesterol and egg intakes with ovarian cancer risk. A weakly positive, but non-linear association, was observed for saturated fat intake (pooled multivariate RR = 1.29, 95% CI: 1.01–1.66 comparing highest versus lowest decile). Results for histologic subtypes were similar. Overall, fat, cholesterol and egg intakes were not associated with ovarian cancer risk. The positive association for saturated fat intake at very high intakes merits further investigation.

Relation of Anthropometric Measurements to Ovarian Cancer Risk in a Population-based Case–control Study (United States)

Abstract Objective  To examine the relationship between anthropometric measures and ovarian cancer by menopausal status.

Consumption of Alcoholic Beverages and Risk of Lung Cancer: Results from Two Case–control Studies in Montreal, Canada

Abstract Objective  To investigate the association between consumption of alcoholic beverages and lung cancer risk.

Use of the Spatial Scan Statistic to Identify Geographic Variations in Late Stage Colorectal Cancer in California (United States)

Abstract Objectives  To identify geographic variations in colorectal cancer by stage at diagnosis in California using a descriptive analysis coupled with a spatial analysis and to discuss methodological considerations concerning the spatial statistical method.

Abstract  It has been shown that methionine depletion inhibits tumor cell growth and reduces tumor cell survival. A novel fusion protein targeted specifically to tumor cells was developed. The fusion protein contained two components: the amino terminal fragment of human urokinase (amino acids 1–49) that binds to the urokinase receptor protein expressed on the surface of invasive cancer cells, and the enzyme l-methioninase (containing 398 amino acids) which depletes methionine and arrests the growth of methionine-dependent tumors. The influence of the fusion protein on the growth and motility of human breast cancer cells was examined using a culture wounding assay. It was determined that MCF-7 breast cancer cells, used in this study, were methionine-dependent and that the fusion protein bound specifically to urokinase receptors of the surface of the cancer cells. Further treatment of the cancer cells with fusion protein over the concentration range 10–8 to 10–6 M produced a dose-dependent inhibition of both the migration and proliferation index of MCF-7 cells in the culture wounding assay over a period of 1 to 3 days. The results of this study suggest that this novel fusion protein may serve as a prototype for specific targeting of methioninase and perhaps other cytotoxic agents to cancer cells.

Epidemiology of treatment-associated mucosal injury after treatment with newer regimens for lymphoma, breast, lung, or colorectal cancer

Abstract   Goals of work: Oral and gastrointestinal (GI) mucositis are frequent complications of chemotherapy and radiotherapy for cancer, contributing to not only the morbidity of treatment but its cost as well. The risk associated with specific chemotherapeutic agents, alone and in combination, has been characterized previously. In the current study, we sought to estimate the risk associated with newer regimens for the treatment of non-Hodgkin’s lymphoma (NHL) and common solid tumors. Methods: We reviewed published studies reporting phase II and III clinical trials of dose-dense regimens for breast cancer and NHL, TAC (docetaxel, adriamycin, cyclophosphamide) chemotherapy for breast cancer, and infusional 5-fluorouracil-based regimens for colorectal cancer. Platinum-, gemcitabine-, and taxane-based regimens for lung cancer, either alone or in combination with radiotherapy, were also considered. Using modified meta-analysis methods, we calculated quality-adjusted estimates of the risk for oral and GI mucositis by tumor type and regimen. Case reports are used to emphasize the relevance of the findings for patient care. Main results: Our findings demonstrate that mucosal toxicity remains an important complication of cancer treatment. Moreover, innovations in drug combinations, scheduling, or mode of administration significantly modulate the risk for both oral and GI mucositis. Conclusions: Ongoing review of the clinical trial experience will remain important as newer, targeted agents enter standard clinical practice.

Total cystectomies in the surgical treatment of rectal cancer with prior chemoradiation: analysis of postoperative morbidity and survival

AbstractBackground and aims  Curative surgery for rectal cancer seldom requires urinary tract resections. The study investigated morbidity and survival following resection of rectum with total cystectomy following chemoradiation for primary rectal cancer.

A prospective study of fish, marine fatty acids, and bladder cancer risk among men and women (United States)

Abstract Objective  To evaluate prospectively the association between intakes of fish, marine fatty acids, and bladder cancer risk in two ongoing cohorts, the Health Professionals Follow-up Study and the Nurses’ Health Study.

Mitocans as anti-cancer agents targeting mitochondria: lessons from studies with vitamin E analogues, inhibitors of complex II

Abstract  Recently mitochondria in cancer cells have emerged as the Achilles heel for tumour destruction. Anti-cancer agents specifically targeting cancer cell mitochondria are referred to as ‘mitocans’. These compounds act by destabilising these organelles, unleashing their apoptogenic potential, resulting in the efficient death of malignant cells and suppression of tumour growth. Importantly, at least some mitocans are selective for cancer cells, and these are represented by the group of redox-silent vitamin E analogues, epitomised by α-tocopheryl succinate (α-TOS). This compound has proven itself in pre-clinical models to be an efficient anti-cancer agent, targeting complex II of the respiratory chain to displace ubiquinone binding. We propose that disrupting the electron flow of mitochondrial complex II results in generation of superoxide, triggering mitochondrial destabilisation and initiation of apoptotic pathways. Moreover, α-TOS is selective for cancer cells with their reduced anti-oxidant defenses and lower esterase activity than the normal (non-malignant) counterparts. In this mini-review we discuss the emerging significance of mitocans, as exemplified by α-TOS.

Overexpression of cyclooxygenase-2 in gastric cancer correlates with the high abundance of vascular endothelial growth factor-C and lymphatic metastasis

Abstract  Cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF)-C are closely related with the development and metastasis of tumors. The gene expression of COX-2 and VEGF-C in gastric cancer and the correlation between them were investigated; 64 paraffin-embedded gastric cancer samples and 22 flesh gastric cancer samples were tested by using immunohistochemistry and the reverse transcription polymerase chain reaction (RT-PCR) technology, respectively. The mean expressive density of COX-2 and VEGF-C mRNA in gastric cancer, with β-actin coamplified as an internal standard, were both significantly higher than those in non-cancerous gastric mucosa (1.363±0.351 vs 0.763±0.304, 0.972±0.331 vs 0.314±0.215, p<0.001). The positive rates of COX-2 and VEGF-C in 64 gastric cancer samples were 72% and 64% respectively. Their expression in the lymph-node metastasis groups were higher than that of the non-lymph-node metastasis groups (p<0.05). Moreover, there was a close correlation between COX-2 and VEGF-C expression levels (p<0.05). The study indicates gastric tumor tissues that produce COX-2 and VEGF-C may have a higher lymphatic invasion and metastatic potential. COX-2 may participate in VEGF-C lymphangiogenic pathway and the high expression of them may play an important role in the lymphatic proliferation and spread in gastric cancer.

Frailty modelling of colorectal cancer incidence in Norway: Indications that individual heterogeneity in risk is related to birth cohort

Abstract  Some cancer types level off or decrease in incidence at older age groups, not following the Weibull hazard rate. This stagnation can be explained by the frailty model, which describes the population effect of mixing individuals who are susceptible, with high risk of cancer, with those that are ‘non-susceptible’, with a low risk of cancer even in the oldest age groups. The aim of the study was to apply a frailty model on colorectal cancer incidence data for the Norwegian population aged 40–99 years, diagnosed 1956–2000. The model provided an acceptable fit to the data. The estimated proportion of susceptibles increased from about 5% to about 24% from the first cohort (1851–1855) to the last cohort (1946–1950), in line with the rise in incidence of the disease during this period. According to the frailty modelling, the estimated number of genetic events necessary for a malignant lesion to develop in the colorectum is seven to eight, which accords with the present knowledge regarding colorectal carcinogenesis. The frailty phenomenon may thus be present in this cancer form. The findings indicate that it is possible to model the development of colorectal cancer in the population based on large heterogeneity in risk between individuals, in such a manner that a small group of individuals are susceptible to develop the disease, whereas the remaining majority have a low susceptibility.

No Association Between p73 G4C14-to-A4T14 Polymorphism and the Risk of Lung Cancer in a Korean Population

A member of the p53 family, p73 may play an important role in the development of lung cancer. Variations in the DNA sequence in the p73 gene can lead to alterations in the production of p73 and/or activity, which can affect an individual’s susceptibility to lung cancer. To test this hypothesis, this study examined the association between the G4C14-to-A4T14 polymorphism in the p73 gene and the risk of lung cancer in a Korean population. The p73 G4C14-to-A4T14 genotypes were determined in 582 lung cancer patients and 582 healthy age- and gender-matched control subjects. Compared with the GC/GC genotype, the GC/AT and the AT/AT genotypes were not significantly associated with the risk of lung cancer [adjusted odds ratio (OR) = 1.08, 95% confidence interval (CI) = 0.84–1.38; and adjusted OR = 1.37, 95% CI = 0.83–2.24, respectively]. In addition, the risk estimate for the combined variant genotype (GC/AT + AT/AT) was similar to that of the GC/GC genotype (a dominant model for the AT allele, adjusted OR = 1.12, 95% CI = 0.88–1.41). These results suggest that the p73 G4C14-to-A4T14 polymorphism does not significantly affect susceptibility to lung cancer in the Korean population.

Associations among Salivary Cortisol, Melatonin, Catecholamines, Sleep Quality and Stress in Women with Breast Cancer and Healthy Controls

Dysregulations in several biological systems in breast cancer patients have been reported, including abnormalities in endocrine and sympathetic nervous system indices, as well as psychological disturbances and sleep disorders. The purpose of this exploratory study was to compare women with breast cancer to healthy control women on measures of salivary cortisol, urinary catecholamines, overnight urinary melatonin, and self-reported sleep quality, symptoms of stress, depression, anxiety and mood disturbance, to determine if discernable patterns of dysregulations across systems were apparent. Thirty-three women were tested in each group, with an average age of approximately 52 years, primarily Caucasian and well-educated. Forty percent of the women with breast cancer had stage 2 disease and they were an average of 1.36 years post-diagnosis. Women with breast cancer had significantly higher levels of disturbance on all the psychological indices, but there were no differences between groups on any of the biological measures, with the exception that the control women had higher dopamine values than the participants with breast cancer. None of the psychological scores were correlated with the biological measures. These results are consistent with other studies of early-stage breast cancer and highlight the importance of considering disease characteristics when investigating endocrine and sympathetic nervous system functioning.

Synthetic peptide YY analog binds to a cell membrane receptor and delivers fluorescent dye to pancreatic cancer cells

Abstract  Pancreatic cancer continues to have a dismal prognosis despite multimodality treatment plans. Peptide YY (PYY) is a gut hormone that suppresses pancreatic exocrine and endocrine function. Previous experiments have shown that shortened synthetic PYY(22-36) analog decreases pancreatic cancer cell growth while also decreasing intracellular cyclic adenosine monophosphate. Our purpose was to construct an optimal synthetic PYY analog that binds to pancreatic cancer cells that may be used for imaging and therapy. Biotinylated PYY analogs with lengths ranging from PYY(l-36), PYY(9-36), PYY(14-36), PYY(22-36), and PYY(27-36) were tested with flow cytometry and receptor cross-linking studies to measure cell membrane binding. Growth inhibition studies were also performed using monotetrazolium tests to determine potency of various PYY analogs. Quantitative flow cytometry reveals the highest specific binding of PYY(14-36) to pancreatic cancer cells. Cross-linking studies reveal a receptor on the cell membrane of human pancreatic ductal adenocarcinoma cells. Growth inhibition studies reveal that PYY (14-36) has the highest potency against PANC-1 and MiaPaCa-2 cells. A novel synthetic PYY analog binds to the cell surface of pancreatic cancer cells and has the ability to deliver fluorescent dyes. The strategy of using biotinylated peptides to deliver avidin-dye complexes to cancer cells will allow imaging of pancreatic tumors and delivery of therapeutic agents.

Lack of association of fragile histidine triad ( FHIT ) polymorphisms with lung cancer in the Korean population

Abstract  The fragile histidine triad (FHIT), which was located on chromosome 3p14.2, was currently considered a promising candidate for a tumor suppressor gene. FHIT performed a crucial function in the tumorigenesis of lung cancer. The inactivation of FHIT via genetic alterations, including the chromosomal deletions and aberrant transcription, are often associated with lung cancer. In this study, the association between FHIT and lung cancer development was evaluated in a study of Korean patients. A total of 299 Korean lung cancer patients and 296 control subjects were recruited into this study. Direct DNA sequencing and TaqMan analysis were employed. Logistic regression analyses were conducted in order to characterize the association between FHIT polymorphisms and lung cancer risk. Via direct sequencing in 24 Korean individuals, 27 sequence variants were identified. Eleven of these polymorphisms were selected for a larger scale genotyping (n = 595). Our finding indicated that the polymorphisms and haplotypes in the FHIT gene are not associated with lung cancer in the Korean population.

Dietary carbohydrate, glycemic index, and glycemic load and the risk of colorectal cancer in the BCDDP cohort

Abstract Background  There is considerable support for associations between insulin and IGF-I levels and colorectal cancer. Diet may relate to colorectal cancer through this mechanism, for example, diets high in glycemic index, glycemic load and/or carbohydrate are hypothesized to increase insulin load and the risk of insulin resistance, hyperinsulinemia. Case–control studies support this hypothesis, but prospective cohorts have had mixed results.

Receptor-dependent growth inhibition of human pancreatic cancer by 9- cis retinoic acid

Abstract  Pancreatic cancer continues to be a lethal disease and ranks as the fifth major cause of cancer death with a 2-year survival rate of only 8%. Although significant progress has been made in the surgical management of this malignancy, there have been only minimal advances in adjuvant therapy. Based on the lack of effective adjuvant or primary therapy for these patients, we tested the effects of various retinoids (all-trans, 9-cis, and 13-cis retinoic acids) on the growth of several human pancreatic cancer cell lines. Four human pancreatic cancer cell lines, designated PANC-1, ASPC, BxPc, and HPAF, were studied. Three types of retinoic acid were added to subconfluent monolayers of the different cancer cell lines over a range of concentrations (1 to 20 μmol/L). Effects on cell growth were determined daily over 96 hours by a cell proliferation assay (MTT). Nuclear receptor (RAR/RXR) transcript and protein were determined by reverse transcription polymerase chain reaction and Western blot analyses. Three (PANC-1, ASPC, and BxPc) pancreatic cancer cell lines responded in a dose-dependent fashion with a significant decrease in cell growth at clinically relevant concentrations of 9-cis retinoic acid (7.5 to 10 μmol/L). All-trans and 13-cis retinoic acid did not affect cell growth in the four pancreatic tumors.

The effects of CYP1A1 gene polymorphism and p16 gene methylation on the risk of lung cancer in a Chinese population

Abstract Objective  To investigate the relationship between the genetic polymorphism of CYP1A1 and the genetic susceptibility to lung cancer as well as to study the effects of the methylation in p16 gene on the risk of lung cancer in a Chinese population.

Plasma homocysteine as a metabolic risk factor for breast cancer: findings from a case–control study in Taiwan

Abstract  Homocysteine (Hcy) is an intermediary product in methionine metabolism and an elevation in plasma Hcy is a sensitive biomarker for an imbalance in the integrated pathways of one-carbon metabolism. More recently, there has been interest in the potential links between total Hcy, folate and cancer. In this study, the association of plasma Hcy levels with the breast cancer risk was investigated. Questionnaire information and blood samples were taken before treatment from 146 women with newly diagnosed, histologically confirmed breast cancer and 285 age-matched control women who were admitted for health examination. Plasma levels of Hcy and folate were measured by enzyme conversion immunoassay and radioassay, respectively. Dietary intake of B-group vitamins was estimated using a semi-quantitative dietary questionnaire. Logistic regression was used to calculate odds ratios (ORs) and their 95% confidence intervals (CIs). Elevated plasma Hcy levels were significantly linked to increased risk of breast cancer (adjusted OR = 2.89, 95% CI  = 1.70-4.92 for the highest tertile as compared with the lowest tertile). Moreover, a similar pattern of enhanced breast cancer risk at higher plasma Hcy levels was observed in both pre-menopausal and post-menopausal women. And this consistent pattern did not differ substantially by level of dietary intake of B-group vitamins. The current study results seem to suggest a possibility that the plasma Hcy levels could be a metabolic risk factor for breast cancer. Future studies are needed to prove causality and provide insight on the mechanism of action of Hcy in breast tumorigenesis.

A Significant Correlation between Nuclear CXCR4 Expression and Axillary Lymph Node Metastasis in Hormonal Receptor Negative Breast Cancer

Abstract Background and objectives  In breast cancer, the expression pattern of CXCR4 may be correlated with the degree of axillary lymph node involvement. The aim of this study was to evaluate the contributing factors that contribute to the correlation between CXCR4 expression and axillary lymph node metastasis in breast cancer.

A phase II trial of weekly 1-hour paclitaxel as second-line therapy for endometrial and cervical cancer

Abstract Background  The efficacy of weekly paclitaxel has not been well characterized in either cervical or endometrial cancer.

A plant oxylipin, 12-oxo-phytodienoic acid, inhibits proliferation of human breast cancer cells by targeting cyclin D1

Abstract  Cyclin D1 overexpression has been associated with poor prognosis and resistance to therapy in human breast cancer. Thus, the development of therapeutic agents that selectively target cyclin D1 activity is of clinical interest. This study demonstrates that 12-oxo-phytodienoic acid (OPDA), a phytohormone with critical functions in growth and development in plants, induces growth arrest in MDA-MB-231 and T47D breast cancer cells. In response to OPDA treatment, the human breast cancer cell lines exhibit a progressive decline in cyclin D1 expression, which is tightly associated with the accumulation of hypophosphorylated form of the retinoblastoma protein (Rb) and G1 arrest. The decrease in cyclin D1 protein expression accompanies a dramatic decline in nuclear but not membranous β-catenin expression and activation of glycogen synthase kinase-3-beta (GSK3β) caused by inhibition of its serine-9 phosphorylation. The proteasome inhibitor MG132 blocks OPDA-mediated decrease in cyclin D1. In addition, the overexpression of T286A, a cyclin D1 mutant which is refractory to phosphorylation by GSK3β and proteosomal degradation, is resistant to OPDA-mediated Rb dephosphorylation as well as G1 cell cycle arrest. Thus, our results demonstrate that degradation of cyclin D1 protein is a key event in OPDA induced growth inhibition in breast cancer cells. These data provide the basic foundation for future efforts to develop OPDA-based approaches in the prevention and treatment of breast cancer and other types of cancer.

Single nucleotide polymorphism D1853N of the ATM gene may alter the risk for breast cancer

Abstract Purpose  Various ATM (ataxia telangiectasia-mutated) mutations and polymorphisms have been reported to be associated with an increased breast cancer risk. Recent studies have produced contradictory results regarding the association between ATM genetic variants and breast cancer risk.

A nationwide epidemiologic study of breast cancer incidence followingbreast reduction surgery in a large cohort of Swedish women

Summary  While it has been demonstrated that prophylactic mastectomy reduces breast cancer incidence among women at high risk, many women often consider this disfiguring surgery unacceptable. One alternative approach may be breast reduction surgery. In order to evaluate the long-term incidence of breast cancer following surgical removal of breast tissue, we have extended by 9 years the follow-up period of our earlier retrospective cohort study of Swedish women electing cosmetic breast reduction surgery (n=30,444) between 1965 and 1993, yielding an average of nearly 16 years of follow-up. Cancer incidence through 2002 was ascertained via the Swedish Cancer Registry. Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were calculated comparing women who underwent breast reduction surgery with women in the general Swedish population. Breast cancer was observed in 443 women versus 624 expected for a statistically significant reduced SIR of 0.71 (95% CI=0.65–0.78). Analyses by age at surgery, time since surgery or calendar year of surgery revealed similar reductions in risk. Our study of over 30,000 women with long-term follow-up offers further evidence that women undergoing breast reduction surgery have reduced breast cancer risk. As the evidence from large-scale cohort studies accumulates, direct testing of this reduction in risk through clinical trials should be considered.

Cancer and aging: symposium of the 27th annual meeting of the Japanese society for biomedical gerontology, Tokyo

Abstract  Although many hypotheses have been proposed to explain the strong link between aging and cancer, the exact mechanisms responsible for the increased frequency of occurrence of cancer with advancing age have not been fully defined. Recent evidence indicates that malregulation of the apoptotic process may be involved in some aging process as well as in the development of cancer. Although it is still under debate how apoptosis is expressed during aging in vivo, this phenomenon is an important factor in unwinding the complicated mechanisms that link cancer and aging. In this review, we report on the discussion at the symposium of the 27th annual meeting of the Japanese society for biomedical gerontology, regarding recent findings from aging and carcinogenesis studies using animal models, the characteristics of cancer in patients with Werners syndrome, the epigenetic changes in human cancers and aging, and the characteristics of human cancers in the elderly. It was concluded that apoptosis plays a role in the aging process and carcinogenesis in vivo, likely as an inherent protective mechanism against various kinds of damages to genes/chromosomes.

Colorectal Cancer Incidence Among Female Textile Workers in Shanghai, China: A Case-cohort Analysis of Occupational Exposures

Abstract  Previous studies have suggested increased risks of colorectal cancers among textile industry workers, potentially related to synthetic fibers. To investigate risks of colon and rectum cancers in relation to these and other textile industry exposures, we conducted a case-cohort study nested within a cohort study of female employees from the Shanghai Textile Industry Bureau (STIB). Cox proportional hazard regression modeling was used to estimate hazard ratios (HR) for colon and rectum cancers associated with duration of employment (e.g., 0, >0 to <10, 10 to <20 years, ≥20 years) in various jobs classified according to process type and exposures to specific agents. Our findings indicate that certain long term exposures may pose increased risk of colorectal cancers, especially dyes and dye intermediates with colon cancer (≥20 years exposure versus never, HR=3.9; 95% CI: 1.4–10.6), and maintenance occupation (HR = 2.3; 95% CI: 1.0–5.7) and metals exposure (HR = 2.0; 95% CI: 1.1–3.6) with rectum cancer. A decreased risk of rectum cancer was associated with exposure to natural fibers such as cotton (HR = 0.7; 95% CI: 0.5–0.9), and a trend of decreasing rectum cancer incidence was observed by category of cumulative quantitative cotton dust or endotoxin exposures, when exposures were lagged by 20 years.

Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its Interaction with the Androgen Receptor (United States)

Abstract  Objective To determine whether directly observed prostate-specific antigen (PSA) promoter diploid haplotype, either alone or in conjunction with androgen receptor (AR) genotype, is associated with prostate cancer risk. Methods We conducted a case–control study nested within the US population-based Cardiovascular Health Study cohort. Incident prostate cancers were identified by linkage to cancer registry records for the years 1989–2000. We genotyped 193 cases and 391 controls for the PSA −252 G/A and −158 G/A SNPs and the AR CAG microsatellite, and developed methods to directly determine proximal PSA promoter haplotypes. Exact logistic regression was used to estimate odds ratios and significance levels.

Decline in Cervical Cancer Incidence and Mortality in New South Wales in Relation to Control Activities (Australia)

Abstract Background  To examine time trends in cervical cancer incidence and mortality in NSW women aged ￥20 years in relation to important health service initiatives and programs.

Incidence of BRCA1 and BRCA2 mutations in 54 Chilean familieswith breast/ovarian cancer, genotype–phenotype correlations

Summary  Our aim was to analyze the incidence of mutations in BRCA1 and BRCA2 genes in 54 families with breast/ovarian cancer. Families were selected from three Institutions following the standard criteria for hereditary breast/ovarian cancer. PCR amplification of all exons was performed, followed by SSCP, heteroduplex, PTT and sequencing analysis. We identified eight truncation mutations, three in the BRCA1 gene and five in the BRCA2 gene. Three of these mutations have not been reported previously by other groups: 308insA in one family, 3936 C>T in two families, for BRCA1, and 4970insTG in one family for BRCA2. In addition two families having Ashkenazi Jewish ancestors present the well known mutations 185delAG and 6174delT. Interestingly, 5 out of 11 families have mutations recurrent in Spanish families. Among the 54 families selected, seven have breast and ovary cancer cases, and only two presented a mutation in BRCA1 or BRCA2 genes. Other cancers as prostate and stomach are frequent among relatives carrying the mutation. Five cases of very early onset (<31 years old) breast cancer were detected. The frequencies of BRCA1 (0.074) and BRCA2 (0.13) mutations in our families is low but similar to the incidence found in other populations, like in Spain. Since is widely known that risk factors that modulate the development of breast cancer such as lifestyle risk factors, geographic location, country of origin and socioeconomic status, besides a familial history of breast cancer our findings suggest that the history of colonization and immigrations is very relevant when studying hereditary factors associated to breast cancer.

Differences in the Pattern of Presentation and Treatment of Proximal and Distal Gastric Cancer: Results of the 2001 Gastric Patient Care Evaluation

Abstract Background  While the overall incidence of gastric cancer has declined in the United States of America, the incidence of proximal gastric cancers has increased. The purpose of this analysis was to highlight key differences between proximal and distal gastric cancer as they relate to presentation and treatment.

Unexplained inversion of the incidence ratio of colon and rectal cancer among men in East Germany. A time trend analysis including 147,790 cases

Abstract Introduction  The incidence rate ratio of colon to rectal cancer is usually about 2:1. It has been observed for a while that the incidence of colon cancer among men (as opposed to women) in the Former German Democratic Republic (GDR) is lower than the rate of rectal cancer. Detailed analyses of this phenomenon have not been done so far. The aim was to give insights in this observation by detailed incidence and mortality analyses and to explore the worldwide ratio of colon and rectal cancers based on population-based cancer registry data.

Pertes, renoncements et intégrations: les processus de deuil dans les cancers

Résumé:  Le modèle du travail de deuil est utilisé pour comprendre les différentes pertes liées au cancer. Perte de l’illusion d’immortalité lors de l’annonce du cancer, perte de l’idéal de santé, perte d’aptitudes physiques et du bien-être, perte de la vie sont autant de bouleversements psychiques qui entraînent des remaniements. La mentalisation de ces pertes va permettre la mise en représentation, la symbolisation puis la transformation des expériences corporelles et physiologiques chargées d’affects en pensées de plus en plus organisées. La révélation traumatique du diagnostic de cancer est un exemple de deuil compliqué, voire impossible et l’usure liée à la maladie chronique peut entraîner une dépression au long terme. Enfin, la période terminale d’un cancer pose la question de la distinction du diagnostic différentiel entre deuil de soi et dépression existentielle pathologique. Les médecins et les soignants, s’ils favorisent le processus du deuil, seront à même de limiter les troubles anxiodépressifs et de l’adaptation dans le cas d’une maladie dont la fréquence augmente, de patients dont la durée de vie s’allonge et dont la demande de qualité de vie augmente.

Pertes, renoncements et intégrations: les processus de deuil dans les cancers

Résumé:  Le modèle du travail de deuil est utilisé pour comprendre les différentes pertes liées au cancer. Perte de l’illusion d’immortalité lors de l’annonce du cancer, perte de l’idéal de santé, perte d’aptitudes physiques et du bien-être, perte de la vie sont autant de bouleversements psychiques qui entraînent des remaniements. La mentalisation de ces pertes va permettre la mise en représentation, la symbolisation puis la transformation des expériences corporelles et physiologiques chargées d’affects en pensées de plus en plus organisées. La révélation traumatique du diagnostic de cancer est un exemple de deuil compliqué, voire impossible et l’usure liée à la maladie chronique peut entraîner une dépression au long terme. Enfin, la période terminale d’un cancer pose la question de la distinction du diagnostic différentiel entre deuil de soi et dépression existentielle pathologique. Les médecins et les soignants, s’ils favorisent le processus du deuil, seront à même de limiter les troubles anxiodépressifs et de l’adaptation dans le cas d’une maladie dont la fréquence augmente, de patients dont la durée de vie s’allonge et dont la demande de qualité de vie augmente.

Experience of high-dose-rate brachytherapy for head and neck cancer treated by a customized intraoral mold technique

Abstract  Radiotherapy of head and neck cancer has become more successful with the advances in treatment modalities and use of a multidisciplinary approach. Higher quality treatment and a team approach to radiotherapy have thus been required for head and neck cancer. This study presents the clinical experience of high-dose-rate (HDR) brachytherapy for head and neck cancer treated by a customized intraoral mold technique. Two patients are reported for whom we created dental prostheses as the radiation carriers for HDR brachytherapy of their head and neck cancers. HDR brachytherapy with the dental prostheses reported here was feasible and effective for eradicating the head and neck cancer. It has been demonstrated that HDR brachytherapy using a customized intraoral technique can be a treatment option for patients who are not candidates for surgery or external irradiation. It is strongly suggested that specialized dentists are needed who are familiar with not only the anatomy and function of the head and neck region but also radiotherapy. Dental radiologists should take responsibility for constructing irradiation prostheses. If they do, they have the potential to improve the quality of life of patients who undergo radiotherapy for head and neck cancer.

Variations in Pelvic Dimensions Do Not Predict the Risk of Circumferential Resection Margin (CRM) Involvement in Rectal Cancer

Abstract Background  The objective of this study was to assess the value of preoperative pelvimetry, using magnetic resonance imaging (MRI), in predicting the risk of an involved circumferential resection margin (CRM) in a group of patients with operable rectal cancer.

Association between up-regulation of fas ligand expression and apoptosis of tumor-infiltrating lymphocytes in human breast cancer

Summary  In order to study the significance of FasL expression in immune escape of breast cancer, FasL protein expression and the number of tumor-infiltrating lymphocytes (TILs) in 40 specimens of breast cancer were detected by immunohistochemitry. The expression of FasL mRNA was measured by in situ hybridization in the consecutive tissue slices of 40 breast cancers respectively. By using terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), apoptotic cells were detected in 40 specimens of breast cancer. The expression of FasL was detected in all 40 specimens to varying degrees. In the consecutive tissue slices, the location of expression of FasL protein corresponded with that of FasL mRNA. In those with FasL extensive expression, the number of TILs was less (P<0.05), the apoptotic index (AI) of TILs was higher and the AI of tumor cells was lower (P<0.01) than those with FasL weak expression respectively. The AI of TILs was correlated with that of tumor cells (r-−0.629, P<0.01). In conclusion, breast cancer cells can induce the apoptosis of TILs through the expression of FasL, which can counterattack the immune system. This may be a mechanism of immune evasion in breast cancer.

The clinical significance of 99mTc-MIBI breast imaging in the diagnosis of early breast cancer

Abstract  Objective: To find an effective, sensitive, specific and noninvasive diagnostic method of breast cancer. Methods: 109 masses of 102 patients with breast lesions smaller than 2 cm in diameter were divided into three groups to undergo 99mTc-MIBI imaging and compared with the results of pathology examination. 20 cases without breast lesions were selected as control. Abnormal condensation of 99mTc-MIBI in the breast reaching 10% higher than that in the counterpart of the healthy breast was regarded as positive. Results: Of 32 breast cancers, positive imaging appeared in 25. Negative imaging were found in 31 of 38 benign breast lesions. Of 39 occult breast lesions, positive imaging appeared in 6 and 3 of them were breast cancer, 2 of 3 patients with slightly increased 99mTc-MIBI imaging threshold were breast cancer also. No positive imaging was found in the control group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of 99mTc-MIBI was 88.4%, 89.2%, 88.0%, 75.0% and 95.3%, respectively. Conclusion: 99mTc-MIBI imaging had higher sensitivity and accuracy in the diagnosis of breast cancer and differentiation between benign and malignant breast lesions. It could provide useful information for the diagnosis of clinically suspected breast cancer.

Mutant Bik gene transferred by cationic liposome inhibits peritoneal disseminated murine colon cancer

Abstract  Peritoneal carcinomatosis of intraabdominal malignancies, such as pancreatic, ovarian, gastric, and colorectal cancers, represents an unmet medical need as conventional cancer treatments rarely eliminate these tumors. Satisfactory treatment for either peritoneally disseminated tumors or prevention of local recurrence after surgery is yet to be developed. To improve the efficacy of novel strategies against peritoneal metastasis, a sensitive, and less invasive model is needed to scrutinize the in vivo tumor growth and response to experimental therapeutics. To study this we intraperitoneally inoculated CT-26 stably expressing luciferase (CT-26-Luc) to mimic tumor spreading within the abdomen. Bioluminescent signals emitted from the living experimental mice correlate well with the injected cell numbers as well as the weights of dissected tumors. Since a nonviral cationic liposome coupled mutant pro-apoptotic gene, Bik(T33D/S35D) (BikDD), was previously shown to have potent anti-cancer effects on an orthotopic breast cancer animal model (Li et al., Cancer Res 63(22):7630-7633, 2003), we evaluated the inhibitory effect of BikDD on the growth kinetics of intraperitoneally inoculated CT-26-Luc. We found that intraperitoneal (i.p.) injection of liposome coupled BikDD suppressed the expansion of CT-26-Luc and prolonged life span of experimental mice. These results suggest a therapeutic effect of BikDD gene therapy on peritoneal carcinomatosis of colon cancer.

Biological significance and the related molecular mechanism of Ets1 mRNA expression in lung cancer by tissue microarray (TMA)

Abstract Objective  To investigate the expressions and molecular mechanism of Ets-1 mRNA, and TGFβ1 and c-Met proteins in the pathogenesis, progression of lung cancer by tissue microarray (TMA) method.

Contribution of the BRCA1 and BRCA2 mutations to breast cancer in Tunisia

Abstract  Hereditary breast cancer accounts for 3–8% of all breast cancers, with mutations in the BRCA1 and BRCA2 genes responsible for up to 30% of these. To investigate the prevalence of BRCA1 and BRCA2 gene mutations in breast cancer patients with affected relatives in Tunisia, we studied 36 patients who had at least one first degree relative with breast and/or ovarian cancer Thirty-four 34 patients were suggestive of the BRCA1 mutation and two were suggestive of the BRCA2 mutation, based on the presence of male breast cancer detected in their corresponding pedigrees. Four mutations in BRCA1 were detected, including a novel frame-shift mutation (c.211dupA) in two unrelated patients and three other frameshift mutations – c.4041delAG, c.2551delG and c.5266dupC. Our study is the first to describe the c.5266dupC mutation in a non-Jewish Ashkenazi population. Two frameshift mutations (c.1309del4 and c.5682insA) were observed in BRCA2. Nineteen percent (7/36) of the familial cases had deleterious mutations of the BRCA1 or BRCA2 genes. Almost all patients with deleterious mutations of BRCA1 reported a family history of breast and/or ovarian cancer in the index case or in their relatives. Our data are the first to contribute to information on the mutation spectrum of BRCA genes in Tunisia, and we give a recommendation for improving clinical genetic testing policy.

Using Multivariate Capture-Recapture Techniques and Statewide Hospital Discharge Data to Assess the Validity of a Cancer Registry for Epidemiologic Use

Abstract   Background: Cancer surveillance is essential for assessing patterns of cancer. State cancer registries do not capture all cases. We used a statewide hospital discharge file to estimate the capture rate and determine biases in capture by a state cancer registry. Methods: We merged the Virginia hospital discharge file and cancer registry for 1995, then used multivariate two- source capture-recapture techniques to control for heterogeneity and more accurately estimate the number and characteristics of missing breast, lung, colorectal and prostate cancer cases.

Trends in the incidence of gastric cancer in Japan and their associations with Helicobacter pylori infection and gastric mucosal atrophy

AbstractBackground  Although age-adjusted mortality from gastric cancer has been decreasing in Japan, the crude incidence of gastric cancer shows a slight increase.

Prostate-derived Ets transcription factor (PDEF) downregulates survivin expression and inhibits breast cancer cell growth in vitro and xenograft tumor formation in vivo

Abstract  Previous studies using immunohistochemistry suggest that loss of the expression of the prostate-derived Ets transcription factor (PDEF) is a strong indicator for cancer cell malignancy. However, the underlying mechanism for this has not been well elucidated. We determined the role of PDEF in breast cancer cell growth and tumor formation using a series of experiments including Western blotting, promoter-luciferase reporter assay, RNA interference technology and a mouse xenograft model. We also determined the relationship between PDEF expression in human breast tumor specimen and cancer patient survivability. These studies revealed that PDEF expression is inversely associated with survivin expression and breast cancer cell xenograft tumor formation. PDEF-specific shRNA-mediated silencing of PDEF expression resulted in the upregulation of survivin expression in MCF-7 cells, which was associated with increased cell growth and resistance to drug-induced DNA fragmentation (apoptosis). In contrast, survivin-specific siRNA-mediated silencing of survivin expression decreased MCF-7 cell growth. Ectopic expression of PDEF inhibited both survivin promoter activity and endogenous survivin expression. Importantly, shRNA-mediated silencing of PDEF expression in MCF-7 breast cancer cells enhanced survivin expression and xenograft tumor formation in vivo. Furthermore, loss of PDEF expression in breast cancer tissues tends to be associated with unfavorable prognosis. These studies provide new information for the role of PDEF and survivin in breast cancer cell growth and tumor formation.

Sex steroid hormones in young manhood and the risk of subsequent prostate cancer: a longitudinal study in African-Americans and Caucasians (United States)

Abstract Objective  To investigate the relation of sex hormone levels in young adults to subsequent prostate cancer risk.

Significant differences in nipple aspirate fluid protein expression between healthy women and those with breast cancer demonstrated by time-of-flight mass spectrometry

Abstract  New approaches are needed for the early detection of breast cancer. Proteomic profiling technologies, such as surface-enhanced laser desorption ionization mass spectrometry (SELDI-MS), may be able to identify tumor markers in biological fluids. The objective of this study was to determine whether there are differences in protein expression patterns in nipple aspirate fluid (NAF) from the cancerous and noncancerous breasts of patients with unilateral breast cancer and the breasts of healthy volunteers. Paired NAF samples were obtained from 23 women with stage I or II unilateral invasive breast carcinoma and five healthy female volunteers. Aliquots of the samples were applied to SELDI Protein-chip arrays (WCX2 and IMAC3-Cu++), and protein expression was analyzed using time-of-flight MS. A total of 463 distinct peaks were detected and analyzed. In breast cancer patients, no differences in protein expression were identified between the breast with the intact primary carcinoma and the contralateral noncancerous breast. Seventeen peaks were overexpressed in cancer-bearing breasts compared to breasts of healthy volunteers (p p < 0.0027). SELDI-MS was able to identify differences in the phenotypic proteomic profile of NAF samples obtained from patients with early-stage breast cancer and healthy women. Proteomic screening techniques such as SELDI-MS analysis of NAF may be useful for breast cancer screening and diagnosis.

Glutathione S -transferase M1 and P1 polymorphisms and risk of breast cancer and fibrocystic breast conditions in Chinese women

Abstract  Enzymes encoded by the glutathione S-tranferase mu 1 (GSTM1) and pi 1 (GSTP1) genes, which are expressed in breast tissue, catalyze the detoxification of endogenous and exogenous electrophiles. Reduced enzyme activity, due to carriage of the GSTM1 deletion or the GSTP1 Ile105Val Val allele, may therefore affect susceptibility to breast cancer and related conditions. In a case-control study of Chinese women, we examined whether these polymorphisms were associated with risk of breast cancer and fibrocystic breast conditions. Women diagnosed with breast cancer (n = 615) or fibrocystic breast conditions (n = 467) were compared to women without clinical breast disease (n = 878). We also examined whether these associations differed by menopausal status or by presence of proliferation in the extra-tumoral epithelium among women with breast cancer and in lesions among women with fibrocystic conditions. No overall association of either GST polymorphism with risk of breast cancer or fibrocystic breast conditions was observed. There was some evidence of slightly elevated cancer risk associated with carriage of the GSTM1 null genotype and at least one GSTP1 105–Val allele (OR = 1.33, 95% CI, 0.99–1.80), compared to carriage of the GSTM1 non-null and GSTP1 Ile/Ile genotypes. This relationship was stronger in women who had breast cancer with extra-tumoral tissue proliferation (OR = 1.77, 95% CI, 1.03–3.04). Our results suggest that GSTM1 and GSTP1 genotypes do not individually influence susceptibility to breast cancer or fibrocystic breast conditions. The observed increased risk of breast cancer associated with joint carriage of the GSTM1 null genotype and GSTP1 105–Val allele needs confirmation in other studies.

The oncologic benefit of high ligation of the inferior mesenteric artery in the surgical treatment of rectal or sigmoid colon cancer

Abstract Purpose  It remains controversial as to whether high ligation of the inferior mesenteric artery (IMA) should be performed during surgical treatment for sigmoid colon or rectal cancer. The purpose of this study is to attempt to clarify the extent of the oncologic benefit of high ligation of the IMA.

Psychometric testing of the Impact of Event Scale-Chinese Version (IES-C) in oral cancer patients in Taiwan

AbstractGoals of work  No culturally relevant instrument exists to assess the impact of cancer on patients in Taiwan. Therefore, this two-phase study was undertaken to (1) develop a Chinese version of the Impact of Event Scale (IES), (2) examine its psychometric properties, and (3) use the IES-Chinese version (IES-C) to assess the impact of cancer in newly diagnosed oral cancer patients in Taiwan.

A single nucleotide polymorphism in the MMP-1 promoter is correlated with histological differentiation of gastric cancer

AbstractPurpose  Matrix metalloproteinase-1 (MMP-1) plays a key role in cancer invasion and metastasis by degradation of extracellular matrix (ECM) and basement membrane barriers. The 1G/2G single nucleotide polymorphism (SNP) in the MMP-1 promoter at position –1607 bp has been reported to affect the transcriptional activity. In the light of these findings, we investigated whether this SNP in theMMP-1 promoter is associated with the development, differentiation, and progression of gastric cancer.

Axial BMD, change in BMD and bone turnover do not predict breast cancer incidence in early postmenopausal women

Abstract  Previous studies have indicated a relationship between bone mineral density and the incidence of breast cancer in middle-aged and elderly women, with women with higher BMD being at significant increased risk. We investigated whether there was such a relationship in younger women who were perimenopausal or in their early postmenopausal years. As part of a population-screening program for osteoporosis, 5,119 women aged between 45 and 54 years were scanned between 1990–1994 at the Osteoporosis Research Unit. In 1997–2001, 3,884 returned for follow-up scans and questionnaires, and 3,144 returned a postal questionnaire in 2002. All cases of incident breast cancer were noted. One hundred sixty-six women indicated that they had suffered from breast cancer, of which 87 were incident cases (59 had prevalent breast cancer at baseline and 20 had benign or unconfirmed diagnosis and were excluded because of the use of agents that may interfere with BMD, e.g., tamoxifen). We compared therefore the incident breast cancer group (BC group; n =87) with a control group (C group; n =3,013). There were no significant differences using a t -test between the BC group and C group for baseline DXA of the spine or femoral neck. Further changes in BMD over a mean period of 6.9 years demonstrated no significant hazard ratio for the lumbar spine or femoral neck. No relationship was seen between the bone turnover markers pyridinoline/creatinine or deoxypyridinoline/creatinine assessed at their second study visit and incidence of breast cancer. In conclusion, in perimenopausal or early postmenopausal women there is no relationship between the incidence of breast cancer and BMD, change in BMD or bone turnover.

Postoperative follow-up of patients with colorectal cancer: a combined evaluation of CT scan, colonoscopy and tumour markers

Abstract Background   The purpose of this study is to present the experience of our department regarding the importance of the systematic postoperative follow-up of patients with colorectal cancer, early diagnosis and treatment of the recurrence of the disease or a metachronous cancer.

Predicting Biopsy Outcome After Mammography: What Is the Likelihood the Patient Has Invasive or In Situ Breast Cancer?

AbstractBackground  As many as 1,000,000 breast biopsies are performed annually in the United States. Although substantial effort has been devoted to estimating breast cancer risk, there have been no studies to predict outcome in women undergoing breast biopsy.

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population

Abstract  Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. As the incidence of lung cancer is known to differ according to ethnicity, we have conducted a case-control study of 146 South Indian lung cancer patients along with 146 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of lung cancer in our population. The current weight of evidence from our study indicated that the frequency of CYP1A1 MspI homozygous variant alleles was significantly higher in cases (OR=3.178). We observed a considerable difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=2.472, 95% CI: 1.191–5.094, P=0.014). There was no relative risk in GSTM1 null genotype when analysed singly (P=0.453). Considering genotype combinations, risk of lung cancer increased remarkably significantly in individuals having one variant allele of CYP1A1, GSTM1, or GSTT1, suggesting gene–gene interactions. Rare genotypic combinations (such as CYP1A1 wild GSTM1 or GSTT1 either null; CYP1A1 variant both GSTM1 and GSTT1 present; CYP1A1 variant GSTM1 or GSTT1 either null), were at higher risk compared to the reference group. Moreover, patients who had smoked <20 pack years and harboured the CYP1A1 variant allele or the GSTT1 null genotype also had a significant risk of lung cancer. Hence our study—the first to analyse a South Indian population—suggests the importance of combined CYP1A1, GSTM1 and GSTT1 polymorphisms in the development of smoking-induced lung cancer.

Dietary and cancer–related behaviorsof vitamin/mineral dietary supplementusers in a large cohort of French women

Summary Background  Several epidemiological studies suggested an association between vitamin/mineral dietary supplement use and cancer risk. However, characteristics of supplement users may themselves be related to cancer risk, and therefore could confound such etiological studies. Very little is known about the characteristics of French supplement users.

Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York

Abstract  The gene encoding catechol-O-methyltransferase (COMT), critical to the inactivation of reactive catechol estrogens, has several single nucleotide polymorphisms (SNPs) that influence enzyme activity. A 3-SNP haplotype (IVS1+255 C>T; Ex4-12 G>A; 3′UTR-521 A>G), which has been shown to reduce COMT expression in the human brain, has been identified. To evaluate the influence of genetic variation of COMT on breast cancer risk, these 3-SNPs were genotyped in 1052 cases and 1098 controls. We estimated the associations between breast cancer and individual SNPs, as well as, multilocus haplotypes. We also examined surrogates of hormone exposure as potential modifiers of the putatively functional Ex4-12 SNP-breast cancer association. Odds ratios (OR) and 95% confidence intervals (CI) were based on age-adjusted unconditional logistic regression models. We found no association between the individual SNPs alone and breast cancer. When examining the association between breast cancer and the 3-SNP haplotypes, we observed a 19% increase in risk associated with each copy of the TGG haplotype (OR=1.19, 95% CI 0.96–1.49), relative to the common TAA haplotype, which was statistically significant when assuming a dominant model (OR=1.32, 95% CI 1.05–1.67, p-value=0.02). In this report of COMT haplotypes and breast cancer, we found some evidence that additional genetic variability beyond the Ex4-12 G>A SNP contributes to risk of breast cancer among a small subgroup of women; however, these results need to be replicated in additional studies.

UV, latitude, and spatial trends in prostate cancer mortality: All sunlight is not the same (United States)

Abstract Objective  We showed previously that Caucasian mortality rates from prostate cancer for 1970–1979 are significantly inversely correlated with ultraviolet (UV) radiation. We now present the analysis of prostate cancer mortality data over a 45-year period (1950–1994) in order to examine the persistence of this pattern. Furthermore, because vitamin D synthesis does not occur during winter months at latitudes higher than 40° N, we examined this relationship above and below 40° N latitude.

Combined profile of the tandem repeats CAG, TA and CA of the androgen and estrogen receptor genes in breast cancer

AbstractPurpose  Case–control studies have reported inconsistent results concerning the association between polymorphisms in the androgen and estrogen receptor (ER) genes and breast cancer. While several studies investigated the association between the androgen receptor (AR) gene, CAG repeat and breast cancer, for the CA and TA repeats in the ER genes there are considerably fewer studies (one for CA and none for TA).

Assistance nutritionnelle à domicile chez le patient pris en charge pour une pathologie cancéreuse

Résumé:   Le séjour hospitalier ne représente plus qu’une petite partie dans l’histoire de la prise en charge du cancer. L’installation et l’aggravation de la dénutrition associée au cancer, se déroulent essentiellement hors h?pital. Le r?le de ce dernier est de détecter les risques de dénutrition, d’initier la prise en charge et de collaborer au suivi des traitements au domicile. La nutrition parentérale à domicile (NPD) est indiquée en périopératoire de chirurgie majeure chez le sujet dénutri, pour le traitement des séquelles digestives et dans le cadre de la phase palliative avec occlusion. La nutrition entérale à domicile (NED), quand à elle, trouve surtout ses indications en postopératoire de certaines chirurgies digestives, et pour la prise en charge des tumeurs des voies aérodigestives supérieures (VADS). Quand au suivi diététique et aux compléments nutritionnels oraux (CNO) leur intérêt a été prouvé en radiothérapie.

Screening for large rearrangements of the BRCA2 gene in Spanish families with breast/ovarian cancer

Abstract  Germ-line mutations in BRCA1 and BRCA2 are responsible for about 30–60% of the hereditary breast and ovarian cancer (HBOC). A large number of point mutations have been described in both genes. However, large deletions and duplications that disrupt one or more exons are overlooked by point mutation detection approaches. Over the past years several rearrangements have been identified in BRCA1, while few studies have been designed to screen this type of mutations in BRCA2. Our aim was to estimate the prevalence of large genomic rearrangements in the BRCA2 gene in Spanish breast/ovarian cancer families. The multiplex ligation-dependent probe amplification (MLPA) was employed to search gross deletions or duplications of BRCA2 in 335 Spanish moderate to high-risk breast/ovarian cancer families previously screened negative for point mutations by conventional methods. Four different and novel large genomic alterations were consistently identified by MLPA in five families, respectively: deletions of exon 2, exons 10–12 and exons 15–16 and duplication of exon 20 (in two families). RT-PCR experiments confirmed the deletion of exons 15–16. All patients harbouring a genomic rearrangement were members of high-risk families, with three or more breast/ovarian cancer cases or the presence of breast cancer in males. We provide evidence that the BRCA2 rearrangements seem to account for a relatively small proportion of familial breast cancer cases in Spanish population. The screening for these alterations as part of the comprehensive genetic testing can be recommended, especially in multiple case breast/ovarian families and families with male breast cancer cases.

Cytochrome P450 1A1 ( CYP1A1 ) T3801C and A2455G polymorphisms in breast cancer risk: a meta-analysis

Abstract  The cytochrome P450 1A1 gene (CYP1A1), encoding Phase I metabolic enzymes, appeared to be a candidate gene for breast cancer risk. However, studies on the association between polymorphisms in this gene and breast cancer have yielded conflicting results. We performed a meta-analysis to investigate the association with breast cancer of the CYP1A1 polymorphisms T3801C (9,316 cases and 12,714 controls) and A2455G (9,552 cases and 9,320 controls). In the genotype contrast of A2455G, both additive [GG vs AA, P = 0.04, fixed-effects OR 0.72; 95% CI (0.53–0.99), P = 0.95 for heterogeneity] and recessive [GG vs (GA + AA), P = 0.04, fixed-effects OR 0.73; 95% CI (0.53–0.99), P = 0.97 for heterogeneity] models produced significant results in east-Asians. In pre-menopausal women in a worldwide population, significant association between A2455G and breast cancer was also found using both models [additive model: P = 0.02, fixed-effects OR 0.52; 95% CI (0.29–0.92), P = 0.39 for heterogeneity; recessive model: P = 0.02, fixed-effects OR 0.51; 95% CI (0.29–0.90), P = 0.38 for heterogeneity]. Our meta-analysis suggests that an A2455G G/G genotype is associated with a trend of reduced breast cancer risk, both in east-Asian women and in pre-menopausal women worldwide, while the T3801C C allele might not be a risk factor for breast cancer. Larger scale primary studies are required to further evaluate the interaction of CYP1A1 polymorphisms and breast cancer risk in specific populations.

DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population

Abstract  The purpose of this study was to evaluate the role of polymorphisms in DNA repair genes as genetic indicators of susceptibility to familial and sporadic breast cancer. We analysed DNA samples from 285 breast cancer patients and 442 control subjects, for XRCC1 Arg399Gln, XPD Lys751Gln, RAD51 G135C and XRCC3 Thr241Met polymorphisms using PCR-RFLP. We observed that women carriers of XRCC1 399Gln genotypes and without family history of breast cancer have a protective effect concerning this disease (OR = 0.54 95% CI 0.35–0.84; p = 0.006). Furthermore, we found that carriers of XRCC3 241Met genotypes without FH have an increased susceptibility of breast cancer (OR = 2.21 95% CI 1.42–3.44; p < 0.001). Additionally, we verified an increased risk of breast cancer in women with FH and carrying RAD51 135C genotypes (OR = 2.17 95% CI 1.19–3.98; p = 0.012). Our results suggest XRCC1 Arg399Gln and XRCC3 Thr241Met DNA repair polymorphisms as important biomarkers to sporadic breast cancer susceptibility, as well as, RAD51 G135C polymorphism as a real risk modifier in familial breast cancer cases.

Detection of Minimal Gastric Cancer Cells in Peritoneal Washings by Focused Microarray Analysis with Multiple Markers: Clinical Implications

Abstract Background  Peritoneal cytology is an important prognostic factor of gastric cancer. However, peritoneal cytology requires great skill, which may explain its low prevalence. A reverse transcriptase–polymerase chain reaction–based assay with multiple marker genes or immunocytochemistry was assessed as an alternative method of gathering the same kind of data as cytology.

Preoperative serum levels of c-erbB-2 do not seem to be useful in management of patients with rectal cancer

Abstract Background and aim  Soluble c-erbB-2 oncoprotein has been proven as a useful marker in the management of breast cancer patients, but its value in diagnostics and follow-up of colorectal cancer patients remains controversial. The aim of this study was to evaluate the usefulness of serum c-erbB-2 monitoring in diagnostics and prediction of disease outcome in rectal cancer patients.

Body size, weight change, fat distribution and breast cancer risk in Hispanic and non-Hispanic white women

Abstract Introduction  The incidence of breast cancer varies among women living in the Southwestern part of the US. We evaluate how body size influences breast cancer risk among these women.

Utilizing Quantitative Polymerase Chain Reaction to Evaluate Prostate Stem Cell Antigen as a Tumor Marker in Pancreatic Cancer

AbstractBackground  Real-time quantitative polymerase chain reaction (qPCR) may prove to be a sensitive technique by which to evaluate potential tumor markers in pancreatic cancer.

Men’s theories about benign prostatic hyperplasia and prostate cancer following a benign prostatic hyperplasia decision aid

Abstract   OBJECTIVE: To use qualitative methods to explore audiotape evidence of unanticipated confusion between benign prostatic hyperplasia (BPH) and prostate cancer in using a videotape BPH treatment decision aid (DA). DESIGN: Qualitative analysis of semi-structured interviews and surveys originally collected to study men’s interpretation of a DA.

Pancreatic cancer and medical history in a population-based case–control study in the San Francisco Bay Area, California

Abstract Objective  To determine the association between pancreatic cancer and medical conditions.

Bridging the gap: decision-making processes of women with breast cancer using complementary and alternative medicine (CAM)

Abstract Goals of work  The purpose of this study was to explore the personal and social processes women with breast cancer engaged in when making decisions about complementary and alternative medicine (CAM). The overall aim was to develop a conceptual model of the treatment decision-making process specific to breast cancer care and CAM that will inform future information and decision support strategies.

Meeting information needs on cancer-related fatigue: an exploration of views held by Italian patients and nurses

Abstract Background  Interest in cancer-related fatigue has been growing over the last two decades and efforts have been dedicated to investigate this topic. However, research addressing the adequacy of educational resources for patients with this distressing and common symptom is lacking. Only one study has been undertaken and this explored Swiss and British patients’ views.

The willingness of general practitioners to be involved in the follow-up of adult survivors of childhood cancer

Abstract Background  Long-term follow-up of childhood cancer survivors is mainly organised by paediatric oncologists and until now general practitioners (GPs) are rarely involved. To ensure appropriate follow-up for all survivors into adulthood, a combined effort of paediatric oncologists and general practitioners might be the solution. We investigated the willingness of GPs, who had followed a postgraduate course on late effects of cancer treatment, to participate in a shared care model for follow-up of adult childhood cancer survivors as well as what their requirements would be in case of participation.

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