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.
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:The aim of our study was to investigate the distribution of glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) gene polymorphism in hepatocellular carcinoma (HCC) and nasopharyngeal carcinoma (NPC) patients in a high risk area in Guangxi Zhuang Autonomous Region,China.Methods:It was a case-control study.The genotypes of GSTM1 and GSTT1 in 181 HCC and 126 NPC patients were compared with 641 matched control.The GSTM1 and GSTT1 genotypes were detected using conventional multiplex PCR method.Results:The frequency of GSTM1 null genotype in HCC,NPC and control groups were 65.2%,61.9% and 47.6% respectively,significant difference between these two cancer groups and control was observed (P < 0.01).The frequency of GSTT1 null genotype in HCC,NPC and control groups were 57.5%,62.7% and 43.1% respectively,significant difference between these two cancer groups and control was observed (P < 0.01).Conclusion:The distributions of GSTM1 and T1 genes are polymorphic in HCC and NPC patients in a high risk area in Guangxi,individuals with GSTM1-null or GSTT1-null would have an increasing risk of developing HCC and NPC,especially when combination with virus infection (HBV or EBV) and absorbed chemical toxin (AFB1 or cigarette).
