Association Analysis Of The BRCA1Major Haplotypes To Sporadic Breast Cancer Risk In Chinese Han Females

Breast cancer is the most popular malignant tumor in women. It is influenced by the interaction among polygenic, environmental and some other complex factors. Nevertheless, given a same environment and so on, the genetic factor will play a key role in breast cancer development. Genetic polymorphisms mainly consist of individual genetic background and is well known to affect different complex diseases including cancers as an important epigenetic factor and, among them, the SNPs (singe nucleotide polymorphisms) might be the most important ones. Mutations in BRCA1is most essentially associated with the risk of breast cancer and is reported to be highly relative to familial transmissibility and the mechanism of early breast cancer. When it comes to the sporadic breast cancer, the BRCA1mutation, however, has never been examined to associate with the pathogenetic mechanism. Thus, the relevance between SNPs of BRCA1or related haplotypes and the risk of sporadic breast cancer is increasingly investigated.Purpose:To detect the association between multiple BRCA1SNPs and the risk of sporadic breast cancer in Chinese Han Females.Methods:Firstly, the BRCA1SNPs and related haplotypes were analyzed bioinformatically. Secondly, an apropriate haplotype-tagging site of2731C>T underwent genotyping by using PCR-PIRA (PCR-primer introduced restriction analysis) and consequent haplotype classification in all the subjects. The statistical significance of haplotype frequency was assessed using SPSS13.0.Results:1) in the BRCA1exon11,13and16, seven SNPs of2201C>T,2430T>C,2731C>T,3232A>G,3667A>G,4427C>T and4956A>G appeared to be interlocked with each other and thus make up two main haplotypes (i.e., the CTCAACA wild-type genotype and the TCTGGTG mutated genotype) in Chinese Han population.2) The BRCA12731C>T genotyping by PCR-PIRA and further haplotype identification were successfully performed in each sample.3) Among the1182affected patients, the BRCA12731genotype makes up427cases (36.2%) of wild-genotype homozygote (i.e.,2731C/C),171cases (14.5%) of mutant homozygote (i.e.,2731T/T) and584patients (49.4%) of heterozygote (i.e.,2731C/T), while in the control group the composition is482(41.2%),158(13.5%) and531(45.3%) correspondingly. Thus, the frequencies between the case and control group for wild-(2731C) and mutant-type allele (2731T) are60.8%vs.63.8%and39.2%vs.36.2%, respectively, which is of statistical significance (P=0.03). Such a result suggests that the BRCA1mutant allele up-regulate the risk of breast cancer among Chinese Han female carriers (OR=1.063[95%CI,1.006～1.124]).