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

来源 :Chinese Journal of Cancer Research | 被引量 : 0次 | 上传用户:pt315311
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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 ( 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 [ie, XRCC3-TM and-MM, adjusted ORs -5.22), respectively] were respectively 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.
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