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Objectives: To detail characterization of mutations and uncharacterized variants in the breast cancer susceptibility genes BRCA1 and BRCA2, as observed in a population of breast cancer patients from the southeastern United States, and to examine baseline characteristics of women referred for counseling and testing and provide a preliminary look at how counseling and testing affected intentions toward prophylactic surgery., Background: Mutations in the BRCA1 and BRCA2 genes give rise to a dramatically increased risk of developing breast or ovarian cancer or both. There are many reports about special populations in which deleterious mutations are present at a high frequency. It is useful to study these genes in more heterogeneous populations, reflecting different geographic regions. Interest in preventive surgery for gene carriers is high in women and their surgeons., Methods: Women were recruited through a prospective clinical trial of counseling and free genetic testing. BRCA1 and BRCA2 were screened for mutations using standard techniques, and results were given to participants. Baseline questionnaires determined interest in preventive surgery at the beginning of the study. Follow-up questionnaires for those who completed testing surveyed interest in prophylactic surgery after counseling and receiving test results., Results: Of 213 women who completed counseling and testing, 44 (20.6%) had 29 separate mutations; there were 11 Jewish women carrying three founder mutations. Twenty-eight women (13.1%) had uncharacterized variants in BRCA1 or BRCA2; nine were not previously reported. Women overestimated their chances of possessing a deleterious gene mutation compared to a statistical estimate of carrier risk. A number of women changed their intentions toward preventive surgery after genetic counseling and testing., Conclusions: Hereditary breast cancer due to mutations in BRCA1 and BRCA2 was a heterogeneous syndrome in the southeastern United States. Most mutations were seen just once, and uncharacterized variants were common and of uncertain clinical significance. In general, positive test results tended to reinforce intentions toward prophylactic surgery. In contrast, women not interested in surgery at the time of entry tended to remain reluctant after testing and counseling.

Objective: To investigate the relationship between polycystic ovary syndrome (PCOS) and ovarian cancer, and to present three hypotheses regarding hormonal factors and the risk of ovarian cancer in women., Methods: Data were analyzed from a population-based, case-control study, the Cancer and Steroid Hormone Study, to test the hypotheses. Four hundred seventy-six subjects with histologically confirmed epithelial ovarian cancer were identified from eight tumor registries of the Surveillance Epidemiology and End Results program. The study included 4081 controls ascertained via random-digit telephone dialing. All subjects and controls were aged 20-54 years., Results: Seven subjects with ovarian cancer and 24 controls reported that they had been diagnosed with PCOS before the study period. Ovarian cancer risk was found to increase 2.5-fold (95% confidence interval [CI] 1.1-5.9) among women with PCOS. This association is found to be stronger among women who never used oral contraceptives (odds ratio [OR] 10.5, 95% CI 2.5-44.2) and women who were in the first quartile of body mass index (13.3-18.5 kg/m2) at age 18 (OR 15.6, 95% CI 3.4-71.0)., Conclusion: The data suggest that the hormonal status of women with PCOS featuring abnormal patterns of gonadotropic secretion (enhanced levels of LH) in lean women may be a mitigating factor for the observed association between PCOS and ovarian cancer. We hope that our preliminary data stimulate further investigation of the testable hypotheses.

Several recent reports have noted an increase risk of breast cancer associated with the use of oral contraceptives (OCs) among various subgroups of young women. These reports spurred us to analyze data from a case-control study in North Carolina of 158 breast cancer patients, 326 hospital controls, and 1140 community controls less than 60 years of age. A logistic regression model was used to calculate odds ratios and 95% confidence intervals and to control for potential confounders. No association between ever-use of OCs and the risk of breast cancer was found for cases compared with either control group. No increased risk was observed for OC use before age 25 or before first full-term pregnancy, or in relation to duration of use, recency of use, or time since first use. Analysis of the subgroup of women less than 45 years of age also showed no relationship between OC use and breast cancer risk. However, an elevated risk of breast cancer was observed among nulliparous women with 5 or more years of OC use in comparisons with hospital controls (odds ratio 7.8) and community controls (odds ratio 2.3). This analysis was based on small numbers of subjects and the 95% confidence intervals touched or overlapped with 1. An unexpected association between duration of OC use and breast cancer risk was found among older premenopausal women in comparisons of cases with both control groups. For these women, a trend was evident in the odds ratio by duration of OC use, and the comparison between cases and community controls was statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)