Ethnic-specific <i>BRCA1/2</i> variation within Asia population: evidence from over 78 000 cancer and 40 000 non-cancer cases of Indian, Chinese, Korean and Japanese populations.

Abstract

Germline mutation in <i>BRCA</i>1 and <i>BRCA2</i> (<i>BRCA</i>) is genetic predisposition for breast and ovarian cancer. Identification of mutation carriers is a critical step to prevent and treat the cancer in the mutation carriers. Human <i>BRCA</i> variation has been well determined as ethnic-specific by studies in Ashkenazi Jewish, Polish and Icelandic populations in the 1990s. However, sufficient evidence is lacking to determine if ethnic-specific <i>BRCA</i> variation is also present in Asia population, which is the largest and the most diversified in modern humans. Our current study aims to investigate ethnic-specific <i>BRCA</i> variation in Asian population. We performed a comprehensive data mining to collect <i>BRCA</i> variation data in Indian, Chinese, Korean and Japanese populations derived from over 78 000 cancer and 40 000 non-cancer cases. We standardised all <i>BRCA</i> variation data following the international standard. We made a systematic comparison between the datasets including variant composition, variation spectrum, variant type, clinical class, founder mutation and high-frequent variants. Our analysis showed that over half of the Asian <i>BRCA</i> variants were Asian-specific, and significant differences were present between the four Asia populations in each category analysed. Data from our study reveal that ethnic-specific <i>BRCA</i> variation is commonly present in Asia population as existing in non-Asian populations. Our study indicates that ethnicity should be an important factor to consider in prevention and treatment of <i>BRCA</i> mutation-related cancer in the Asia population. We recommend that the current <i>BRCA</i> variation databases should include ethnic variation information in order to function as true global <i>BRCA</i> references.