The Association Between GC And CYP24A1 Gene Polymorphisms And Breast Cancer Risk

Breast cancer is the common tumors which lead the main cause of women death.At present,the incidence rate in China grows at a rapid speed per year and shows the younger trend.Therefore,in China,breast cancer has developed into a serious threat problem in public health.Presently,the cause of breast cancer is still unknown and can be attributed to a combination of genetic and environmental factors.However,in the same environment exposure,the risk of breast cancer will be different because of genetic differences,which suggests that genetic factors also play an influence on the development of breast cancer.Therefore,research on the genetic susceptibility of breast cancer is helpful for screening high-risk populations and risk prediction,combining genetic markers and effective preventive measures can reduce the risk of breast cancer.In addition to transporting,solubilizing,and binding vitamin D and its metabolites,vitamin D binding protein(DBP)encoded by the GC gene can also undergo deglycosylation to form DBP-macrophage activating factor(GC-MAF),which plays an antiproliferative and antiangiogenic role in tumors.The CYP24A1 gene is involved in vitamin catabolism,osteoblast differentiation,and vitamin D receptor signaling pathways activation.The expression of CYP24A1 in normal breast tissues is different from that in cancer tissues,and the expression level is higher in breast cancer tissues.Therefore,we speculate that GC and CYP24A1 gene have a great effect on breast cancer.This study was based on the design of case-control study and included related exposure factors to explore the association between GC and CYP24A1 gene polymorphisms and the risk of breast cancer in Chinese population.It may provide a basic help for screening susceptible markers and disease prevention and control.Part IThe Study on Genetic variants in GC Gene and Breast Cancer Risk.[Objective] To investigate the relationship between group-specific component globulin GC gene polymorphisms and breast cancer risk in Chinese population.[Methods] we carried out a population-based case-control study to collect information about 818 newly histopathology or imaging confirmed breast cancer patients and 935cancer-free controls in Wuxi,Jiangsu.We use the Mass ARRAY platform to genotype GC gene polymorphisms(rs16847024,rs17467825,rs3755967 and rs2298850),logistic regression was used to analyze its association with breast cancer risk.[Result] Three SNPs(rs17467825,rs2298850 and rs3755967)can reduce the risk of breast cancer.In stratified analysis,the four SNPs were not related to risk of breast cancer in subgroup of age,menopausal status,and family history.However,in the subgroup with waist circumference of less than 80 cm,rs17467825,rs2298850,and rs3755967 have protective effects on breast cancer risk.We observed the multiplicative interaction between rs2298850 and rs3755967 and waist circumference in breast cancer risk(interaction P values were 0.031 and 0.039,respectively).Additive interaction between rs17467825,rs2298850,and rs3755967 and waist circumference in breast cancer risk were not found.Compared with carrying 0protective alleles,individuals carrying 3-6 protective alleles could reduce 19% risk of breast cancer.[Conclusion] The results show that the GC gene polymorphisms may alter the breast cancer risk in Chinese women.Part IIThe Study on Genetic variants in CYP24A1 Gene and Breast Cancer Risk.[Objective] To explore the association between cytochrome P450 24-hydroxylase CYP24A1 gene polymorphisms and breast cancer risk in Chinese population.[Methods] we carried out a population-based case-control study to collect information about 818 newly histopathology or imaging confirmed breast cancer patients and 935cancer-free controls in Wuxi,Jiangsu.We use the Mass ARRAY platform to genotype CYP24A1 gene polymorphisms(rs2209314,rs2585428,rs2762941,rs3787555,rs4809959,rs912505,and rs927650),logistic regression was used to analyze its association with breast cancer risk and generalized multi-factor dimensionality reduction(GMDR)was applied to explore locus-locus interactions.[Result] None of seven SNPs(rs2209314,rs2585428,rs2762941,rs3787555,rs4809959,rs912505 and rs927650)are in association with the risk of breast cancer.In stratified analysis,the seven SNPs were not related to breast cancer risk in subgroup of age and menopausal status.However,in the subgroup with waist circumference of greater than or equal to 80 cm,rs4809959 increased 20% risk of breast cancer.We observed the multiplicative interaction between rs4809959 and waist circumference in breast cancer risk(interaction P values were 0.023).Additive interaction between rs4809959,rs2585428 and waist circumference in breast cancer risk were found.Locus-locus interaction was not found in breast cancer risk.[Conclusion] The results show that the CYP24A1 gene polymorphism rs4809959 is correlated with risk of breast cancer in Chinese women.