Relationship Between OATP1B1 Gene Polymorphisms And Breast Cancer

Objectives:Multiple genetic and environmental factors contribute to the onset of breast cancer.Genetic factors are related to hereditary breast cancer,while estrogens is one of the most important factor for sporadic breast cancer.Several reports have reported that estrogen is important in the development and progression of breast cancer mainly through estrogen receptor,there are relationships between high estrogen levels and breast cancer risk,and other risk factors were also considered to act through effecting the concentration of estrogen.Meanwhile,tamoxifen,a selective estrogen receptor modulator,has traditionally been the mainstay of adjuvant endocrine therapy in breast cancer patients.Organic anion transporter 1B1 is an important factor in hepatic transport of estrogen sulfate(E1S),various polymorphisms in this gene have been identified. Especially,the 521T/C polymorphisms can effect the concentration of E1S,maybe an implicit risk factor for breast cancer.The aim of this study is to investigate the distribution of allele frequency of OATP1B1 T521/C and its effect on therapeutic efficacy of tamoxifen.Methods:Blood samples were collected from blood samples of 266 breast cancer patients and 146 health controls.OATP1B1 521T/C polymorphisms were determined using PCR-RFLP method.Allele and genotype frequencies were compared between patients and health controls.Allele and genotype frequencies were also compared between different groups which devised by different factors.Results:In breast cancer patients and health controls,the OATP1B1 T521C mutant allele frequency were 11.4%and 10.3%,there were no significant difference between two groups(P=0.345),and there were also no difference about the age of onset and the rate of lymph-node metastasis among three genotype.The frequency of C allele in ER-positive patients is significantly higher than that in ER-negative patients(14%vs 7.8%,P=0.016),in addition,the frequency of CC/TC genotype in ER-positive patients(24.7%) is higher than that in ER-negative patients(15.5).But there were no significant differences in the frequency distribution of OATP1B1 521T/C polymorphisms between pre-menopausal and post-menopausal breast cancer patients.Conclusion:OATP1B1 521T/C polymorphism has no influence on the onset and progression of breast cancer,but the frequency of OATP1B1 521T/C mutant allele in ER-positive patients was higher than that in ER-negative patients,it may influence the effect of endocrine therapy of breast cancer patients.