P4-10-10: Breast Cancer Risk Factors among Asian Versus Caucasian Women with BRCA1/2 Mutations.
de, BMA; Kwong, A; Goldstein, BA; Lipson, JA; Ikeda, DM; McPherson, LA; Sharma, B; Kardashian, A; Schackmann, EA; Kingham, KE; Mills, MA ...
Published in: Cancer Research
BackgroundPrior research suggests that the prevalence and penetrance of BRCA1/2 mutations may be different in Asians compared with Caucasians. Such differences in penetrance could be related to genetic, as well as hormonal, reproductive and lifestyle factors.Methods: Chinese and Caucasian BRCA1/2 mutation carriers were recruited from genetics clinics in Hong Kong and California. We compared personal and family history of cancer, as well as hormonal, reproductive and lifestyle exposures between racial groups. Breast density was estimated using BIRADS breast composition categories on mammogram. We analyzed DNA samples for single-nucleotide polymorphisms (SNPs) that may modify BRCA-associated cancer risk, and compared the prevalence between groups. A multivariable analysis of potential modifiers of cancer risk is underway.Results: Forty-two Chinese women from Hong Kong and forty-nine Caucasian women from California were enrolled. BRCA1 mutations were more common in Caucasian women (63% vs. 43%, P=0.05), while BRCA2 mutations were more common among Chinese women (57% vs. 33%, P=0.02). More Chinese women had a personal history of breast cancer (91% vs. 53%) and ovarian cancer (12% vs. 4%). In contrast, significantly more Caucasian women had a family history of breast and ovarian cancer. On average, Caucasian women had higher parity, breastfed more, had less dense breasts on mammogram, and more often underwent prophylactic oophorectomy, all of which are protective against breast cancer in the general population. However, Caucasian women also consumed more alcohol and had higher average BMI. Risk associated alleles in RAD51, MAP3K1 and TOX3/TNRC9 were more common in Chinese women; risk associated alleles in FGFR2 and RASSF1 were similar in frequency between groups. Results of the multivariable analysis are pending and will be presented.Discussion: We found notable differences between Chinese and Caucasian women in the proportion of BRCA1 versus BRCA2 mutations, and in the distribution of hormonal, reproductive and lifestyle factors, and SNPs associated with breast cancer risk. Such variations in risk-modifying factors may contribute to differences in BRCA mutation penetrance. Enhanced understanding of racial differences in BRCA1/2 mutation epidemiology may inform targeted cancer screening and prevention strategies.Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-10.
