Association Study Of SNPs Within Mirco-RNA Binding Sites In ErbB4and Breast Cancer Risk

ObjectiveBreast cancer is the most frequent malignant tumors in women.Its risk factors include parity、menstrual status、die、exercise and family history,et al.MicroRNAs are noncoding small RNAs that regulate expression by Watson-Crick base-pairing to target mRNA.They are involved in most biological and pathological processes, which includs tumorigenesis.The binding of microRNA to mRNA is critical for regulating the mRNA level and protein expression. ErbB4gene (also known as HER4) is the fourth member of epidermal growth factor receptor (EGFR) family, It regulates cell development, apoptosis and differentiation through the MAPK, PI-3K and a series of cell signaling pathways. We hypothesized that there were association between single-nucleotide polymorphism of microRNA binding sites in ErbB4gene and susceptibility of breast cancer.MethodsA hospital-based case-control study was conducted in Tianjin Medical University Cancer Hospital and Institute from January2005to September2008. A total of1509breast cancer patients and1517healthy controls enrolled in this study. All information was collected by questionnaire through face-to-face interview, which included demographic data, menstrual status, and disease history, family history of cancer, behavior pattern, dietary habit, and social psychological character, clinical data and laboratory data. Polymorphisms of microRNA binding sites in ErbB4gene was assessed by TaqMan method. Two-sided chi square test was used to identify Hardy-Weinberg equivalence and frequency differences between groups. Odds ratios and their95%confidence intervals for breast cancer were derived using univariate and multivariate unconditional logistic regression analysis. Stratified analysis was done by relevant factors at the same time, and then analysis the interaction between genotype and environmental factors.Results 1) For the rs16845990T/A polymorphism,the genotype frequencies of TT\CT and CC were30.69%、48.50%and20.81%in the cases respectively, which were not significantly different from those of nomal controls (28.23%TT、50.91%CT and20.85%CC.)(P=0.302) as well as C allele distribution (P=0.142).2)The genotype distribution of ErbB4polymorphisms in rs1595066was significantly different between cases and controls(x2=6.22,Pvalve=0.045), Multivariate logistic regression analysis showed that the carriers of the AG and AA genotypes were associated with a significantly decreased risk of breast cancer, the individual who carried A variant(AG/AA)had a decreased risk of breast cancer by20.5%(aOR=0.795,95%CI=0.681-0.928).3) Stratified analysis showed that the protective effect was more evident in subjects who were older than55、without history of benign breast disease nor family history of cancer.4)There was no significantly different interaction between rs1595066polymorphisms and age、history of benign breast disease nor family history of cancer(P value are0.104、0.442and0.152respectively)Conclusions1)There was no significantly correlation between rs16845990T/A polymorphism and the susceptibility of breast cancer.2) The genotype distribution of ErbB4polymorphisms in rs1595066was significantly different between cases and controls. A allele was associated with a significantly decreased risk of breast cancer3) The protective effect of A allele of rs1595066G/A polymorphism was more evident in subjects who were older than55、without history of benign breast disease nor family history of cancer.4) More rigorous laboratory studies of ethnically diverse population and functional studies are warranted to confirm our findings.