Abstract Background: There is substantial evidence that breast cancer aggregates within some families, accounting for about 25% of incident cases. Known genetic variants, such as BRCA1/BRCA2 mutations, account for less 25% of these familial breast cancer cases, and furthermore 15-30% of mutation carriers will never develop breast cancer. Thus, research into additional risk or protective factors for familial breast cancer may provide valuable information for risk stratification. There is accumulating epidemiological and experimental evidence that vitamin D, calcium, and dairy, are associated with sporadic breast cancer risk, however it is unknown whether these factors are also associated with familial breast cancer. Methods: To address this question, we conducted a case-control study of probands identified from the UCLA Family Cancer Registry; a population enriched with women with a strong family history of breast cancer and BRCA1/BRCA2 mutation carriers. This study included 612 unrelated women who developed breast cancer and 497 unaffected controls within the registry recruited between 1998 and 2006. All participants completed a detailed survey questionnaire that examined reproductive and lifestyle factors, various health and screening behaviors, as well as information on a variety of putative breast cancer risk or protective factors including vitamin D and calcium supplement use (yes or no) and dairy consumption (servings per day). Multivariate logistic regression models controlling for confounding factors were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of vitamin D, calcium, and dairy with familial breast cancer. Results: Cases and controls were similarly distributed by race (80% were non-Hispanic white) and BRCA1 mutation carrier status (12%), however cases on average were five years older than controls and were more likely to be BRCA2 mutation carriers (12% versus 6%). Vitamin D (OR=0.88, 95% CI=0.63-1.24), calcium (OR=0.73, 95% CI=0.56-0.67), and dairy (OR=0.81, 95% CI=0.65-1.01) were inversely associated with breast cancer in this population. These associations did not appear to be modified by BRCA1 or BRCA2 mutation status. For women with three affected first degree relatives, the breast cancer associations with vitamin D (OR=0.19, 95% CI=0.02-1.8) and calcium (OR=0.29, 95% CI=0.06-1.3) were considerably strengthened; however these associations were not statistically significant. No other vitamins (A, B, C, or E), supplements (herbal remedies), or dietary factors (fruits, vegetables, fiber, or fat) were significantly associated with breast cancer. Conclusion: Calcium supplementation was associated with familial breast cancer, independently of BRCA mutation status, and the vitamin D and calcium associations with breast cancer may be modified by family history. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2813.
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