A single nucleotide polymorphism in the 5' untranslated region of RAD51 and risk of cancer among BRCA1/2 mutation carriers

RAD51 colocalizes with both BRCA1 and BRCA2, and genetic variants in RAD51 would be candidate BRCA1/2 modifiers. We searched for RAD51 polymorphisms by sequencing 20 individuals. We compared the polymorphism allele frequencies between female BRCA1/2 mutation carriers with and without breast or ovarian cancer and between population-based ovarian cancer cases with BRCA1/2 mutations to cases and controls without mutations. We discovered two single nucleotide polymorphisms (SNPs) at positions 135 g-->c and 172 g-->t of the 5' untranslated region. In an initial group of BRCA1/2 mutation carriers, 14 (21%) of 67 breast cancer cases carried a c allele at RAD51:135 g-->c, whereas 8 (7%) of 119 women without breast cancer carried this allele. In a second set of 466 mutation carriers from three centers, the association of RAD51:135 g-->c with breast cancer risk was not confirmed. Analyses restricted to the 216 BRCA2 mutation carriers, however, showed a statistically significant association of the 135 c allele with the risk of breast cancer (adjusted odds ratio, 3.2; 95% confidence limit, 1.4-40). BRCA1/2 mutation carriers with ovarian cancer were only about one half as likely to carry the RAD51:135 g-->c SNP. Analysis of the RAD51:135 g-->c SNP in 738 subjects from an Israeli ovarian cancer case-control study was consistent with a lower risk of ovarian cancer among BRCA1/2 mutation carriers with the c allele. We have identified a RAD51 5' untranslated region SNP that may be associated with an increased risk of breast cancer and a lower risk of ovarian cancer among BRCA2 mutation carriers. The biochemical basis of this risk modifier is currently unknown.

Cancer culture: Epidemics, human behaviour and the dubious search for new risk factors

The rise of melanoma and the almost complete decline of stomach cancer clearly reflect disturbances of human culture during the 20th century. Environmental factors play a dominant role in the epidemiology of melanoma and many other malignancies.

Colorectal cancer screening - what the guidelines don't tell you - letter

The author discusses the recommendation by the NH and MRC for faecal occult blood testing in bowel cancer screening.

Coffee and alcohol consumption and the risk of pancreatic cancer in two prospective United States cohorts

Although most prospective cohort studies do not support an association between coffee consumption and pancreatic cancer, the findings for alcohol are inconsistent. Recently, a large prospective cohort study of women reported statistically significant elevations in risk of pancreatic cancer for both coffee and alcoholic beverage consumption. We obtained data on coffee, alcohol, and other dietary factors using semiquantitative food frequency questionnaires administered at baseline (1986 in the Health Professionals Follow-Up Study and 1980 in the Nurses’ Health Study) and in subsequent follow-up questionnaires. Data on other risk factors for pancreatic cancer, including cigarette smoking, were also available. Individuals with a history of cancer at study initiation were excluded from all of the analyses. During the 1,907,222 person-years of follow-up, 288 incident cases of pancreatic cancer were diagnosed. The data were analyzed separately for each cohort, and results were pooled to compute overall relative risks (RR). Neither coffee nor alcohol intakes were associated with an increased risk of pancreatic cancer in either cohort or after pooling the results (pooled RR, 0.62; 95% confidence interval, 0.27–1.43, for >3 cups of coffee/day versus none; and pooled RR, 1.00; 95% confidence interval, 0.57–1.76, for >=30 grams of alcohol/day versus none). The associations did not change with analyses examining different latency periods for coffee and alcohol. Similarly, no statistically significant associations were observed for intakes of tea, decaffeinated coffee, total caffeine, or alcoholic beverages. Data from these two large cohorts do not support any overall association between coffee intake or alcohol intake and risk of pancreatic cancer.

Postmenopausal Hormone Use, Screening, and Breast Cancer: Characterization and Control of a Bias

Previous investigators have suggested that screening-related biases may explain associations between postmenopausal hormone use and breast cancer. To investigate these biases, we studied postmenopausal women in the Nurses' Health Study from 1988 to 1994. Hormone use is associated with increased subsequent screening. Among women not screened in the previous 2 years, the probability difference, comparing current hormone users with others, for having mammography in the following 2 years is 19.5%; among women previously screened, the difference is 4.9%. These differences persist after control for other factors. If the increase in screening is causal, screening by mammogram could be intermediate in the causal pathway to breast cancer diagnosis. To deal with this problem, we restrict attention to a subset of the cohort in which the effect of postmenopausal hormone use on screening is small (women previously screened). In this subset, the rate ratio comparing breast cancer rates among current postmenopausal hormone users with others is 1.28. In a sensitivity analysis, the bias could not by itself plausibly account for the associations in our data. Our data provide evidence of an association between postmenopausal hormone use and breast cancer that is not solely the product of a detection bias.

The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) - Results of an international collaborative study

Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is an autosomal dominant condition accounting for 2–5% of all colorectal carcinomas as well as a small subset of endometrial, upper urinary tract and other gastrointestinal cancers. An assay to detect the underlying defect in HNPCC, inactivation of a DNA mismatch repair enzyme, would be useful in identifying HNPCC probands. Monoclonal antibodies against hMLH1 and hMSH2, two DNA mismatch repair proteins which account for most HNPCC cancers, are commercially available. This study sought to investigate the potential utility of these antibodies in determining the expression status of these proteins in paraffin-embedded formalin-fixed tissue and to identify key technical protocol components associated with successful staining. A set of 20 colorectal carcinoma cases of known hMLH1 and hMSH2 mutation and expression status underwent immunoperoxidase staining at multiple institutions, each of which used their own technical protocol. Staining for hMSH2 was successful in most laboratories while staining for hMLH1 proved problematic in multiple labs. However, a significant minority of laboratories demonstrated excellent results including high discriminatory power with both monoclonal antibodies. These laboratories appropriately identified hMLH1 or hMSH2 inactivation with high sensitivity and specificity. The key protocol point associated with successful staining was an antigen retrieval step involving heat treatment and either EDTA or citrate buffer. This study demonstrates the potential utility of immunohistochemistry in detecting HNPCC probands and identifies key technical components for successful staining.

The supportive care needs of men with prostate cancer (2000)

The diagnosis and subsequent treatment of prostate cancer is followed by a range of significant disease specific and iatrogenic sequelae. However, the supportive care needs of men with prostate cancer are not well described in the literature. The present study assesses the supportive care needs of men with prostate cancer who are members of prostate cancer self-help groups in Queensland, Australia. In all, 206 men aged between 48 and 85 years (mean = 68) completed the Supportive Care Needs Survey (SCNS) (62% response). The SCNS is a validated measure assessing perceived need in the domains of psychological needs, health system and information needs, physical and daily living needs, patient care and support, and sexuality. Items assessing need for access to services and resources were also included. One third of the sample reported a moderate to high need for help for multiple items in the sexuality, psychological and health system and information domains. Younger men reported greater need in the sexuality domain; living in major urban centres was predictive of greater psychological need; being closer to the time of diagnosis was related to greater need for help in the physical and daily living domain; having prostate cancer that is not in remission, having received radiation therapy, and lower levels of education were predictive of greater need for help in patient care and support. Of the total sample, 55% of men had used alternative cancer treatments in the past 12 months, with younger and more educated men more likely to use alternative therapies. Interventions in sexuality, psychological concerns and informational support are priorities for men with prostate cancer. Copyright (C) 2001 John Wiley & Sons, Ltd.

Long-term outcomes of genetic counseling in women at increased risk of developing hereditary breast cancer Information,

This multicenter study evaluated the impact of genetic counseling in 218 women at risk of developing hereditary breast cancer. Women were assessed prior to counseling and 12-month post-counseling using self-administered, mailed questionnaires. Compared to baseline, breast cancer genetics knowledge was increased significantly at follow-up. and greater increases in knowledge were associated with educational level. Breast cancer anxiety decreased significantly from baseline to follow-up, and these decreases were associated with improvements in perceived risk. A significant decrease in clinical breast examination was observed at the 12-month follow-up. Findings suggest that women with a family history of breast cancer benefit from attending familial cancer clinics as it leads to increases in breast cancer genetics knowledge and decreases in breast cancer anxiety. The lowered rates of clinical breast examination indicate that the content of genetic counseling may need to be reviewed to ensure that women receive and take away the right message. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

A zebrafish homologue of deleted in colorectal cancer (zdcc) is expressed in the first neuronal clusters of the developing brain

DCC (deleted in colon cancer), Neogenin and UNC-5 are all members of the immunoglobulin superfamily of transmembrane receptors which are believed to play a role in axon guidance by binding to their ligands, the Netrin/UNC-40 family of secreted molecules (Cell. Mol. Life Sci. 56 (1999) 62; Curr. Opin. Genet. Dev. 7 (1997) 87). Although zebrafish homologues of the Netrin family of secreted molecules have been reported, to date there has been no published description of zebrafish DCC homologues (Mol. Cell. Neurosci. 9 (1997) 293., Mol. Cell. Neurosci. I I ( 1998) 194; Mech. Dev. 62 (1997) 147). We report here the expression pattern of a zebrafish dcc (zdcc) homologue during the initial period of neurogenesis and axon tract formation within the developing central nervous system. Between 12 and 33 h post-fertilisation zdcc is expressed in a dynamic spatiotemporal pattern in all major subdivisions of the central nervous system. Double-labelling for zdcc and the post-mitotic neuronal marker HNK-1 revealed that subpopulations of neurons within the first nuclei of the zebrafish brain express zdcc. These results support our previous observation that patterning of neuronal clusters in the zebrafish brain occurs early in development (Dev. Bioi, 229 (2001) 271). (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.