GSTM1 and XRCC3 polymorphisms: Effects on levels of aflatoxin B1-DNA adducts
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- Long, X., Ma, Y. & Deng, Z. Chin. J. Cancer Res. (2009) 21: 177. doi:10.1007/s11670-009-0177-6
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.
AFB1-DNA adducts were measured by ELISA, and GSTM1 and XRCC3 codon 241 genotypes were identified by PCR-RFLP.
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.
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.