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 ma...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.展开更多
Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells wer...Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells were obtained from subjects including 140 HCC and 536 controls. The XRCC1 gene 399 codon polymorphism was detected by PCR-RFLP technique. Results: The frequency of XRCC1 399 Arg/Gln & Gln/Gln genotype in HCC patients (48.57%) was significantly higher that in normal controls (32.46%), and XRCC1 399 Arg/Gln & Gln/Gln genotype was associated with increased risk of HCC (adjusted odds ratios (OR)=2.18, 95% confidence interval (CI) 1.27～3.74). In addition, in the cohort of low/median level of AFB1 exposure, the codon 399 Gln allele was associated with a conspicuous significantly increasing risk for HCC (adjusted OR=2.06, 95% CI=1.01～4.20). Conclusion: The results indicate that the XRCC1 399 Gln allele is a potentially important determinant of susceptibility to AFB1-related HCC.展开更多
基金supported by the National Natural Science Foundation of China (No.39860032)the Youth Science Foundation of Guangxi (No.0833097)
文摘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.
基金This work was supported by the NationalNatural Science Foundation of China(No.39860032)
文摘Objective: To explore the relationship of XRCC1 Arg 399 Gln polymorphism and AFB1-related hepatocellular carcinoma (HCC) risk in Guangxi population. Methods: The DNA samples from peripheral blood white blood cells were obtained from subjects including 140 HCC and 536 controls. The XRCC1 gene 399 codon polymorphism was detected by PCR-RFLP technique. Results: The frequency of XRCC1 399 Arg/Gln & Gln/Gln genotype in HCC patients (48.57%) was significantly higher that in normal controls (32.46%), and XRCC1 399 Arg/Gln & Gln/Gln genotype was associated with increased risk of HCC (adjusted odds ratios (OR)=2.18, 95% confidence interval (CI) 1.27～3.74). In addition, in the cohort of low/median level of AFB1 exposure, the codon 399 Gln allele was associated with a conspicuous significantly increasing risk for HCC (adjusted OR=2.06, 95% CI=1.01～4.20). Conclusion: The results indicate that the XRCC1 399 Gln allele is a potentially important determinant of susceptibility to AFB1-related HCC.
