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

Abstract

BackgroundGermline mutation in BRCA1 and BRCA2 (BRCA) 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 BRCA 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 BRCA 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 BRCA variation in Asian population.MethodsWe performed a comprehensive data mining to collect BRCA variation data in Indian, Chinese, Korean and Japanese populations derived from over 78 000 cancer and 40 000 non-cancer cases. We standardised all BRCA 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.ResultsOur analysis showed that over half of the Asian BRCA variants were Asian-specific, and significant differences were present between the four Asia populations in each category analysed.ConclusionData from our study reveal that ethnic-specific BRCA 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 BRCA mutation-related cancer in the Asia population. We recommend that the current BRCA variation databases should include ethnic variation information in order to function as true global BRCA references.

Talazoparib Versus Chemotherapy in Patients with HER2-negative Advanced Breast Cancer and a Germline BRCA1/2 Mutation Enrolled in Asian Countries: Exploratory Subgroup Analysis of the Phase III EMBRACA Trial

“…The spectrum of gBRCA1/2 variants also varies across different ethnic groups; importantly, there is a relatively high frequency of variants of uncertain significance in Asian patients [15]. To investigate this further, a recent study analyzed over 78,000 samples from cancer patients and 40,000 samples from non-cancer patients in Indian, Chinese, Korean, and Japanese populations, and found that over half of the BRCA variants identified were Asian specific [16]. Currently, there is also a paucity of data regarding the use of PARP inhibitors, including talazoparib, in Asian patients, owing to the predominance of Western patients in some breast cancer clinical trials [17][18][19].…”

A Population-Based Analysis of BRCA1/2 Genes and Associated Breast and Ovarian Cancer Risk in Korean Patients: A Multicenter Cohort Study

“…The previous study based on the data from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) has identified that there was a substantial difference in variant type, frequency, and location by geographical region and race or ethnicity [ 10 ]. In addition, over 50% of Asian BRCA variants were Asian-specific, and even among Asian populations (Indian, Chinese, Korean, and Japanese populations) there were significant differences [ 11 ]. For these reasons, we assumed that the patterns and effects of BRCA1 or BRCA2 pathogenic variants related to breast or ovarian cancer in Korean are different than those of other populations (not only non-Europeans but also other Asians).…”

“…However, most of the data are based on European populations. Although it has been suggested that cancer risk and genetic variation vary by populations [ 10 , 11 , 12 ], there is still a lack of research on non-European populations.…”

“…When conducting BRCA1- or BRCA2 -related studies in non-European populations who do not currently have as much clinical data as Europeans, it is important to predict how many samples are needed to resolve the inconclusive state of variants of uncertain significance (VUS). In addition, as it has been suggested that there are distinct differences in clinical characteristics of breast or ovarian cancer [ 13 , 14 , 15 ] and in the spectrum of BRCA1/2 variants between non-Europeans and Europeans [ 10 , 11 , 16 , 17 ], questions arise about whether the cancer risk by pathogenic or likely pathogenic variants (PLPVs) in BRCA1/2 estimated based on Europeans can be used in non-European populations. Here, we performed a comprehensive analysis for BRCA1 / 2 variants and associated cancer risk in Korean patients with respect to VUS and PLPVs in BRCA1 and BRCA2 .…”

<p>Chrysophanol Inhibits the Progression of Diabetic Nephropathy via Inactivation of TGF-β Pathway</p>

“…Diabetic nephropathy (DN) is a frequent type of diabetic complication which results from permanent uncontrolled diabetes, and it usually causes end-stage renal diseases (ESRD). 1,2 In addition, DN also results in increased thickness of the basement membrane, glomerular sclerosis and renal fibrosis. 3,4 Nowadays, the main treatment of DN is drug therapy, 5 while the effect of drug therapy remains limited.…”