The Precision Relationships Between Eight GWAS-Identified Genetic Variants And Breast Cancer In A Chinese Population

Object Breast cancer is the most common type of cancer and the most common cause of cancer deaths among females worldwide.In China,the incidence and mortality of breast cancer is rising rapidly.Early screening and diagnosis of breast cancer has been paid more and more attention.Breast cancer is a complex disease,which is the result of genetic and non-genetic risk factors.In terms of genetic risk factors,Genome-wide association studies（GWASs）have became the main way to discover low-penetrance susceptibility loci [（single nucleotide polymorphism,SNP）],in the past ten years.Due to the linkage disequilibrium（LD）in diverse populations,it still needs to be determined if these SNPs have strong statistical associations with the risk of breast cancer in other populations.Therefore,we selected eight GWAS-identified genetic variants to study their association of breast cancer risk,in a Chinese population.Methods We conducted a case-control study of 1,156 breast cancer patients and 1,256 healthy controls.First of all,a epidemiological survey were carried out among all participants,including demographic data,menstrual,reproductive and breastfeeding history,hormone replacement therapy history,previous benign breast disease history,and their family history of breast cancer,then we set up an epidemiological database about breast cancer.Subsequently,a 3-ml peripheral blood sample was collected to extract genomic DNA,then we established a genetic database of breast cancer.We searched the genetic susceptibility loci for breast cancer risk by the GWAS website of National Institutes of Health（NIH）.After screening,eight SNPs were selected for genotyping.All of the DNA samples were genotyped by SNPscan^TM.The associations between SNPs and the risk of breast cancer were assessed by computing odds ratios（ORs）and 95% confidence interval（CIs）using unconditional logistic regression models with adjustment for potential confounders such as age,age at menarche,and family history of breast cancer.Results We first validated that the SNPs rs12922061,rs2290203,and rs2981578 were associated with overall breast cancer risk in southeast Chinese women,with the per-allele OR of 1.209（95% CI: 1.064-1.372）,1.176（95% CI: 1.048-1.320）,and 0.852（95% CI: 0.759-0.956）,respectively.Rs12922061 and rs2290203 even passed the threshold for Bonferroni correction（P value: 0.00625）.In stratified analysis,we found another five SNPs were significantly associated within different subgroups.However,after Bonferroni correction（P value: 0.000446）,there were no statistically significant was observed.The superposition calculation results showed that the risk of breast cancer was higher with the number of risk alleles.In gene-environment interaction analysis,we observed gene environment interaction is associated with the risk of breast cancer.Conclusions The genetic variants rs12922061,rs2290203 and rs2981578 are associated with overall breast cancer risk in southeast Chinese women.There was a significant association between loci rs10474352,rs10816625,rs2296067,rs4951011 and rs9693444 and the stratification of different subgroups,respectively.The addition of the risk allele could increase the risk of breast cancer.Gene-environment interactions played a potential role of in the risk of breast cancer.