BRCA1 c.2845insA is a recurring mutation with a founder effect in Singapore Malay women with early onset breast/ovarian cancer.

B reast cancer is the third most common form of cancer worldwide, after lung and stomach cancer, and is the most common cause of cancer death in women. The age-adjusted incidence rates of breast cancer are 176% higher in developed than developing countries. In Singapore, breast cancer is the most common cancer in women and the incidence rate in 1993–1997 was 2.3 times higher than in 1968–1972, with an annual increase significantly higher in pre-menopausal than post-menopausal women (5.7% v 3.9%). Of note, the Malay ethnic group in Singapore has shown the greatest increase in the incidence of breast cancer (4.4%) over the past three decades compared with the Chinese and Indian subpopulations. In addition, breast cancer in Malay women has shown a bimodal distribution in age specific incidence, at 45 and 65 years, and a strong birth cohort effect has been noticed in this group. The majority of breast cancer is sporadic, but about 5% to 10% of all breast and ovarian cancer cases are believed to be attributable to the inheritance of germline mutations in high penetrance, autosomal dominant susceptibility genes. The identification and cloning of one such gene BRCA1 (OMIM # 113705) has rapidly led to the characterisation of mutations in this gene among high risk families, as well as early onset breast and/or ovarian cancer patients or tumour series in populations worldwide. Several founder and recurrent mutations have now been identified in specific ethnic groups, such as African-Americans, Ashkenazi Jews, Dutch, Finns, French-Canadians, Icelanders, Japanese, Norwegians, Swedes, and Russians, among others. However, almost all molecular studies of BRCA1 performed have defined breast cancer risks and related genetic factors in Caucasian women of European descent, and studies in Asian populations, although on the increase, have been few. Among these Asian populations, recurrent and founder mutations have now been reported for Japanese, Filipinos, Thais, and Chinese. 22 24–25 Given the increase in the incidence of breast cancer, together with the rise in the number of patients presenting with early onset breast cancer among Singapore Malays, we decided to characterise germline BRCA1 mutations and polymorphic variants in patients presenting with early onset breast or ovarian cancer, with or without a family history, in order to evaluate the proportion of cancers attributable to mutations in this gene.