RESUMO
OBJECTIVE: To explore the association of the Thr241Met polymorphism of X-ray cross-complementing group 3 (XRCC3) gene with genetic susceptibility to aflatoxin B1(AFB-1)-related hepatocellular carcinoma (HCC)in Guangxi population. METHODS: We conducted a hospital-based case-control study, including 257 HCC cases and 711 controls without cancers or liver diseases. The XRCC3 Thr241Met polymorphism was analyzed by PCR. RESULTS: The XRCC3 genotypes XRCC3-Thr/Met or XRCC3-Met/Met were related with an elevated risk of HCC. The risk of HCC was associated with the number of mutant Met copies (adjusted OR were 2.20 and 8.56 for XRCC3-Thr/Met and Met/Met, respectively); moreover, there seemed to be combined effects for HCC risk between the variant genotypes and AFB1-DNA adduct levels from peripheral blood leukocytes (adjusted OR was 2.34 to 20.44, P < 0.01). CONCLUSION: These results suggested that XRCC3 polymorphism may be associated with the risk of AFB1- related HCC among the Guangxi population, and interacts with AFB1 exposure in the development of HCC induced by AFB1.
Assuntos
Aflatoxina B1/toxicidade , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Proteínas de Ligação a DNA/genética , Polimorfismo Genético/genética , Estudos de Casos e Controles , China , Predisposição Genética para Doença/genética , Genótipo , Humanos , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição/genéticaRESUMO
PURPOSE: The relationship between aflatoxin B1 (AFB1) exposure and hepatocellular carcinoma (HCC) has been previously demonstrated and supported with strong epidemiological evidence. However, the role of genetic polymorphism of X-ray cross-complementing group 3 (XRCC3) codon 241 (namely: Thr241Met), which may be involved in the repair of DNA double-strand breaks caused by carcinogens such as AFB1, been less well elaborated. METHODS: We conducted a case-control study including 491 cases and 862 controls to evaluate the associations between this polymorphism and HCC risk for Guangxi population by means of polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: We found that individuals with the XRCC3 genotypes with codon 241 Met (namely XRCC3-TM or XRCC3-MM) had an increased risk of HCC than those with the homozygote of XRCC3 codon 241 Thr alleles (namely XRCC3-TT, adjusted odds ratios 2.22 and 7.19; 95% confidence intervals 1.72-2.88 and 4.52-11.42, respectively). The risk of HCC, moreover, did appear to differ more significantly among individuals featuring high-level AFB1-DNA adducts, whose adjusted odds ratios (95% confidence intervals) were 11.59 (5.73-23.47) and 37.54 (16.32-86.32), respectively. CONCLUSIONS: These findings support the hypothesis that the XRCC3 Thr241Met polymorphism may be associated with the risk of AFB1-related HCC among the Guangxi population.
