Association Study Confirms Two Susceptibility Loci For Breast Cancer In Chinese Han Women

Background: Breast cancer is a cancer of the breast tissue,which can be divided into ductal carcinoma and lobular carcinoma.The main clinical manifestations of breast lumps,nipple retraction,overflow,erosion,breast skin and contour changes,lymph nodes and a series of changes.There will be a distant metastasis in the later stage.Surgical treatment is the main treatment for breast cancer,followed by radiotherapy,chemotherapy and endocrine therapy.Breast cancer is the highest incidence carcinoma in women worldwide.The incidence of breast cancer in Chinese Han population is 27/100 thousand,although it is lower than that in western countries,the incidence is increasing.Breast cancer is a complex disease,its pathogenesis may be the result of environmental and genetic factors,among which genetic factors play an important role.Genetic analysis of breast cancer has been studied by linkage analysis and candidate gene association analysis.With the rapid development of genetic research,At present,scholars in the world use the whole genome association study,It can be used to study the genomes of thousands of unrelated samples at a level that is difficult to achieve,and is not limited by a priori assumptions about disease.Recent genome-wide association studies(GWAS)have discovered more than 100 common genetic susceptibility genes for breast cancer.The GWAS study is most for European and American population,the results are fully applicable to China population is still unknown.Combined with GWAS literatures published at present,other related diseases and subsequent validation of the experimental results,we have good reason to believe that genetics between different ethnic groups have significant heterogeneity.Therefore,for European and American groups of breast cancer GWAS results has been published,it is necessary to further validation experiments were carried out in the crowd.Our research team verified the susceptibility gene loci for breast cancer in the early years of 2014,and found that the susceptibility loci of nine breast cancer genes were related to the Chinese Han population.in recent years,a large number of breast cancer susceptibility loci were reported in the European and American population,so it is necessary to verify whether these susceptible genes / sites are related to the incidence of breast cancer in Chinese Han women.Objective: This study selected from 2014 to 2016,the published study of the European and American GWAS research conducted further validation experiments to determine whether there are susceptible genes / sites related to Chinese Han population.Other studies were conducted to save the screening time and cost of breast cancer susceptibility genes / sites in Chinese Han population.Method: We selected and genotyped 32 single nucleotide polymorphisms(SNPs),a total of 22 susceptibility loci,using the Sequenom i PLEX platform in a female Chinese cohort of 3,036 breast cancer cases and 3,036 healthy controls.Results: We confirmed ten risk-associated variants within three reported breast cancer susceptibility loci in a Chinese Han population: 5q11.2(rs16886181,P=5.29×10-6,OR=1.19;rs1017226,P=5.24×10-4,OR=1.22;rs16886034,P=2.00×10-3,OR=1.21;rs16886113,P=1.24×10-3,OR=1.20;rs16886364,P=9.20×10-4,OR=1.21;rs16886397,P=1.17×10-3,OR=1.20;rs16886448,P=1.62×10-3,OR=1.20;and rs2229882,P=5.14×10-4,OR=1.31),5q14.3(rs421379,P=2.83×10-13,OR=1.83),and 10q26.1(rs35054928,P=7.73×10-6,OR=1.18).10q26.1 was previously reported to be associated with Chinese Han population,and the two sites of 5q11.2 and 5q14.3 are the first to demonstrate that it is associated with breast cancer in Chinese Han women.Conclusions: This study reports three breast cancer susceptibility loci that were previously identified in European populations and are also risk factors for Chinese populations.This study deepens the genetic basis of breast cancer in Chinese Han women.