| Objective:To investigate the relationship between polymorphisms of ER-αand estradiol-synthesizing enzyme genes CYP17,CYP19 with breast cancer risk in Chinese women.Methods:In this case-control study,we genotyped polymorphisms of ER-α(rs3798577)and other two estrogen-metabolizing enzyme genes CYP17(rs743572) and CYP19(rs10046)among 300 breast cancer cases and 390 controls in a Chinese population.The CYP17 rs743572 polymorphism was analyzed using the PCR-restriction fragment length polymorphisms(RFLP)assay;CYP19 rs10046 and ER-αrs3798577 were genotyped using the Taq-Man method according to the manufacturer's instructions.Allele and genotype frequencies among cases and controls were calculated and deviation from the Hardy-Weinberg equilibrium was examined using the chi-square test.Crude and adjusted odds ratios(aORs)and 95% confidence intervals(CIs)were calculated by unconditional logistic regression analyses to estimate an association between these polymorphisms and breast cancer risk.Results:Results from univariate unconditional logistic regression analysis showed that the following factors were significantly associated with the occurrence of breast cancer:times of pregnancy,times of births,age of last pregnance≥30 yesrs,later age of menopause,family history of cancer,smoking habits.High education level and income of family,current alcohol intake,sport times once a week were the protective factors of breast cancer.For the ER-αgene,although the T allele frequency of ER-αwas significantly higher in cases(59.8%)than controls(54.5%)(P=0.047),no difference was found in the genotype distribution.We found significantly increased postmenopausal breast cancer risk only associated with the CYP17 TC genotype(aOR=2.24,95%CI= 1.03-4.87),compared with the TT genotype.The CYP19 variant TC+TT genotypes were significantly associated with both overall risk(TT+TC vs.TT aOR=1.73, 95%CI=1.13-2.65)and premenopausal cancer risk(TT+TC vs.TT aOR=1.78, 95%CI=1.03-3.09).Further stratified analyses showed that the association with CYP19 and ER-αpolymorphisms was stronger for ER-/PR- but not for ER+/PR+ tumors.Furthermore,there was the joint effects between CYP19 T and ER-αT allele genotypes(aOR=1.67,95%CI=1.03-2.69 for CYP19 TC+TT vs.CC among ER-α T variant genotype carriers)and between CYP19 T and CYP17 C variant genotypes (aOR=1.98,95%CI=1.10-3.54 for CYP19 TC+TT vs.CC among CYP17 variant C genotype carriers).Additional stratified analyses of the associations between breast cancer and hormonal risk factors by CYP17,CYP19,and ER-αgenotypes showed that CYP17 TC or C allele genotye,CYP19 T allele genotye,ER-αTT genotye have the joint effect with other reproductive risk factors of breast cancer.The results of multi-logistic analysis between gene factors and the other susceptible factors showed that age of last pregnance≥30 yesrs,total months of breastfeeding＜12,family history of cancer,CYP19 T allele genotype were the independent risk factors of breast cancer.High income of family,current alcohol intake,more sport times once a week were the protective factors of breast cancer.Conclusions:In summary,our results provide evidence that genetic polymorphisms in CYP17(rs743572),CYP19(rs10046)and ER-α(rs3798577)are associated with increased breast cancer risk among Chinese women.We observed that CYP17 TC genotype carriers had significantly increased risk of postmenopausal breast cancer,whereas CYP19 T variant genotypes were significantly associated with overall risk of breast cancer,especially in premenopausal women.In addition,the T allele frequency of ER-αwas significantly higher in breast cancer cases than in controls,CYP19 T and CYP17 C variant genotypes had a joint effect of increasing the risk of breast cancer,and CYP19 T and ER-αT variant genotypes had a joint effect on breast cancer risk.
|
PDF Full Text Request