Ethnic differences in breast and ovarian cancer risk resulting from genetic variation

Ethnic differences in cancer incidence and mortality result from differences in genetic and epidemiological risk factors. Mutations in BRCA1 and BRCA2 account for a small proportion of all breast cancer cases but a much higher proportion of those with a strong family history of breast or ovarian cancer and of those of Ashkenazi Jewish descent. Gerrnline mutations in cancer susceptibility genes have been identified for many races and ethnic groups. Differences in cancer risk among ethnic groups have been recognized, and a proportion of the differences may be the result of founder mutations within these genes. The BRCA2 999del5 mutation in Iceland and the three BRCA1 and BRCA2 mutations in Ashkenazi Jews have been well characterized. Less is known about the contribution of mutations in BRCA1 and BRCA2 outside of European groups. Knowledge acquired by studying the effect of founder mutations in well-defined populations may be applied to larger, more heterogeneous populations. The cost and time required for mutation analysis are reduced considerably when founder mutations are identified for a specific ethnic group. Two case-control studies and one cohort study were conducted to expand current knowledge of genetic susceptibility and its contribution to breast and ovarian cancer rates in populations. Findings pertaining to the prevalence, penetrance of mutations in BRCA1 and BRCA2 and associations with the Androgen Receptor gene polymorphism and consanguinity demonstrate that genetic factors contribute to the relatively high rates of breast and ovarian cancer in the Philippines and Pakistan. Women of Ashkenazi Jewish descent with a family history of either breast or ovarian cancer should be counselled about genetic testing for BRCA1/2 to elucidate their risk level. The studies described within impact the management and identification of women at increased risk of cancers of the breast and ovary.