Genetic Variants In Steroid-metabolizing Enzymes And MiRNA-453 Were Associated With Breast Cancer Risk In Chinese Women

Background and Purpose1) To investigate the relationship between the polymorphism of the estrogen related enzymes and other steroid hormone metabolizing enzymes with breast cancer risk in benign mammary disease and sporadic breast cancer so as to find the possible reasons for the development of the disease.2) To test the hypothesize that genetic variations in miRNAs may influence susceptibility to cancer by performing a genetic association analysis.Methods1) We used 232 breast cancer cases and 123 cancer free controls in the Department of Breast Surgery at Shanghai Cancer Hospital of Fudan University.2) To extract the DNA and to determine the association between SNPs in genes encoding sex steroid-metabolizing enzymes and breast cancer risk. SNP genotyping was used MassARRAY system (Sequenom) by means of matrix assisted laser desorption ionisation-time of flight mass spectrometry method (MALDI-TOF) according to the manufacturers instructions.3) We evaluated the odds ratios (OR) and their 95% confident intervals (95%CI) of the associations between SULT,17β-HSD,STS,miR-453 polymorphism and breast risk among the menopausal status.4) We performed a meta-analysis including ethnic subgroup and menopausal statue subgroup to investigate the association of SULT1Al Arg213His polymorphism with breast cancer.Result1) Our analysis has demonstrated a trend between the AG genotype compared to GG genotype of SNP rs2077412, located in SULT1Al and an increased breast cancer risk (P=0.053, OR=1.791).2) In the subgroup analysis of different menopausal statue, we found TT+GT genotype compared to GG genotype of SNP rs2024159 decreased the risk of breast cancer among postmenopausal women (P=0.03, OR=0.416).3) In the subgroup analysis of different menopausal statue, we surprisingly found that the TT genotype compared to GG genotype SNP rs676378 increased the risk of breast cancer among premenopausal women (OR=3.154, P=0.009) and GG+GT genotype compared to TT genotype decreased the risk of breast cancer among premenopausal women (OR=0.366, P=0.013).Also TG genotype compared to GG genotype decreased the risk of breast cancer among postmenopausal women (P=0.0002, OR=0.052), TT+GT genotype compared to GG genotype increased the risk of breast cancer (OR=10.688,P=0.006), TG+GG genotype compared to TT genotype decreased the risk of breast cancer (OR=0.276,P=0.002).4) Of the three polymorphisms, rs4497679, rs4398102, rs3751860 have exhibited an association with breast carcinoma incidence.5) Our analysis has demonstrated a significantly association between the CC genotype compared to TC genotype of SNP rs56103835 of miR-453 and a reduced breast cancer risk (P=0.041, OR=0.61). In the subgroup analysis of different menopausal statue, we surprisingly found that the CC genotype compared to TC genotype decreased the risk of breast cancer among postmenopausal women but not among premenopausal women (P=0.002, OR=0.19) and TT+CT genotype compared to CC genotype decreased the risk of breast cancer (OR=0.24, P=0.003).6) We found that SULT1Al Arg213His increase the risk of breast cancer among postmenopausal women in the dominant model (OR=1.28, P=0.019) by meta-analysis. Also there was a significant increase in breast cancer risk among Asian women (OR=2.03, P=0.05) but not Caucasian women in recessive model.ConclusionIn a conclusion, this study showed that the polymorphism of SULT and miRNA-453 may have a strong relationship with breast cancer risk, and there is a significant association of the polymorphism of 17(3-HSD, STS miRNA-453 and breast cancer risk in postmenopausal women.