GSTM1 and XRCC3 Polymorphisms:Effects on Levels of Aflatoxin B1-DNA Adducts  

作　　者：Xi-dai Long Yun Ma Zhou-lin Deng 

机构地区：[1]Department of Pathology, Youjiang Medical College for Nationalities, Baise 533000, China [2]Department of Pathology, Guangxi Medical University, Nanning 530021, China

出　　处：《Chinese Journal of Cancer Research》2009年第3期177-184,共8页中国癌症研究（英文版）

基　　金：supported by the National Natural Science Foundation of China (No.39860032);the Youth Science Foundation of Guangxi (No.0833097)

摘　　要：Objective： Aflatoxin B1 （AFB1）, which can cause the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-metabolizing or repairing genotypes may experience an increased risk of genotoxicity. This study was designed to investigate whether the polymorphisms of two genes, the metabolic gene Glutathione S-transferase M1 （GSTM1） and DNA repair gene x-ray repair cross-complementing group 3 （XRCC3）, can affect the levels of AFB1-DNA adducts in Guangxi Population （n= 966） from an AFB1-exposure area. Methods： AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP. Results： The GSTM1-null genotype [adjusted odds ratio （OR） = 2.09; 95% confidence interval （CI） = 1.61-2.71] and XRCC3 genotypes with 241 Met alleles [i.e., XRCC3-TM and -MM, adjusted ORs （95% CI） were 1.43 （1.08-1.89） and 2.42 （1.13-5.22）, respectively] were significantly associated with higher levels of AFB1-DNA adducts. Compared with those individuals who did not express any putative risk genotypes as reference （OR = 1）, individuals featuring all of the putative risk genotypes did experience a significantly higher DNA-adduct levels （adjusted ORs were 2.87 for GSTM1-null and XRCC3-TM; 5.83 for GSTM1-null and XRCC3-MM）. Additionally, there was a positive joint effect between XRCC3 genotypes and long-term AFB1 exposure in the formation of AFB1-DNA adducts. Conclusion： These results suggest that individuals with susceptible genotypes GSTM1-null, XRCC3-TM, or XRCC3-MM may experience an increased risk of DNA damage elicited by AFB1 exposure.Objective： Aflatoxin B1 （AFB1）, which can cause the formation of AFB1-DNA adducts, is a known human carcinogen. AFB1-exposure individuals with inherited susceptible carcinogen-metabolizing or repairing genotypes may experience an increased risk of genotoxicity. This study was designed to investigate whether the polymorphisms of two genes, the metabolic gene Glutathione S-transferase M1 （GSTM1） and DNA repair gene x-ray repair cross-complementing group 3 （XRCC3）, can affect the levels of AFB1-DNA adducts in Guangxi Population （n= 966） from an AFB1-exposure area. Methods： AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP. Results： The GSTM1-null genotype [adjusted odds ratio （OR） = 2.09; 95% confidence interval （CI） = 1.61-2.71] and XRCC3 genotypes with 241 Met alleles [i.e., XRCC3-TM and -MM, adjusted ORs （95% CI） were 1.43 （1.08-1.89） and 2.42 （1.13-5.22）, respectively] were significantly associated with higher levels of AFB1-DNA adducts. Compared with those individuals who did not express any putative risk genotypes as reference （OR = 1）, individuals featuring all of the putative risk genotypes did experience a significantly higher DNA-adduct levels （adjusted ORs were 2.87 for GSTM1-null and XRCC3-TM; 5.83 for GSTM1-null and XRCC3-MM）. Additionally, there was a positive joint effect between XRCC3 genotypes and long-term AFB1 exposure in the formation of AFB1-DNA adducts. Conclusion： These results suggest that individuals with susceptible genotypes GSTM1-null, XRCC3-TM, or XRCC3-MM may experience an increased risk of DNA damage elicited by AFB1 exposure.

关 键 词：Aflatoxin B1 （AFB1） AFB1-DNA adducts GSTM1 XRCC3 POLYMORPHISM 

分 类 号：TS207.4[轻工技术与工程—食品科学] X131[轻工技术与工程—食品科学与工程]