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Abstract: Background: The relationship between Helicobacter pylori infection and gastric antrum adenocarcinoma (GAA) has previously been demonstrated and supported with strong epidemiological evidence. However, the role of genetic polymorphism of X-ray cross-complementing group 3 (XRCC3) Thr241Met (rs#861539), which may be involved in the repair of DNA double-strand breaks caused by carcinogens such as CagA, a protein produced by H. pylori, has been less well elaborated. Methods: We conducted a hospital-based case–control study, including 721 patients with pathologically confirmed GAA and 989 individually matched controls without any evidence of tumors or precancerous lesions to evaluate the associations between this polymorphism and GAA risk in the Guangxi population. XRCC3 codon 241 genotypes and CagA status were determined using TaqMan-PCR and PCR, respectively. Results: Increased risks of GAA were found for cagA-positive individuals [odds ratio (OR), 7.31; 95% confidence interval (CI), 5.87–9.09]. We also found that individuals with the XRCC3 genotypes with codon 241 Met (namely XRCC3-TM or XRCC3-MM) had an increased risk of GAA compared with those with the homozygote of XRCC3 codon 241 Thr alleles (namely XRCC3-TT, adjusted ORs 1.76 and 3.73; 95% CIs 1.37–2.24 and 2.66–5.23, respectively). The risk of GAA, moreover, appeared to differ more significantly among individuals featuring cagA-positive status, whose adjusted ORs (95% CIs) were 11.31 (8.34–15.33) and 27.48 (15.17–49.78), respectively. Conclusion: These results suggest that XRCC3 Thr241Met polymorphism may be associated with the risk of GAA related to CagA. [Copyright &y& Elsevier]

Aim: The X-ray repair cross-complementing group 7 (XRCC7) plays an important role in the repair of DNA double-strand breaks by nonhomologous end-joining repair (NEJR) pathway. However, the role of XRCC7 polymorphisms (rs#7003908 and rs#10109984) possibly influencing NEJR capacity in hepatocellular carcinoma (HCC) induced by aflatoxin B1 (AFB1) has not been well elaborated. Methods: This hospital-based case-control study, including 348 patients with newly diagnosed HCC and 597 controls without any evidence of liver diseases, was conducted to elucidate the association between these two polymorphisms and the risk of HCC related to AFB1 exposure among a Guangxi population from a high AFB1-exposure area by means of TaqMAN-polymerase chain reaction technique. Results: We observed that HCC patients featured higher AFB1 exposure than control group (odds ratios [OR] = 6.49 and 6.75 for exposure years and exposure levels, respectively). Furthermore, these individuals with the genotypes of XRCC7 rs#7003908 G alleles (namely XRCC7-TG or -GG), compared the homozygote of XRCC7 rs#7003908 T alleles (XRCC7-TT), faced increasing risk of HCC (OR, 3.45 and 5.04; 95% confidence intervals [CIs], 2.40-4.94 and 3.28-7.76, respectively). We also found some evidence that this polymorphism interacted with AFB1-expousure years or levels in the process of HCC carcinogenesis. Additionally, XRCC7 rs#7003908 polymorphism was correlated with the levels of AFB1-DNA adducts (r = 0.142, P < 0.001). XRCC7 rs#10109984 polymorphism, however, did not modify the risk of HCC related to AFB1 exposure ( P > 0.05). Conclusion: These data suggest that XRCC7 rs#7003908 polymorphism may be one of the genetic modifiers for AFB1-related HCC among Guangxi population. [ABSTRACT FROM AUTHOR]

Aflatoxin B1 (AFB1) is an important environmental carcinogen and can induce DNA damage and involve in the carcinogenesis of hepatocellular carcinoma (HCC). The deficiency of DNA repair capacity related to the polymorphisms of DNA repair genes might play a central role in the process of HCC tumorigenesis. However, the interaction of DNA repair gene polymorphisms and AFB1 in the risk of hepatocellular carcinoma has not been elucidated. In this study, we investigated whether six polymorphisms (including rs25487, rs861539, rs7003908, rs28383151, rs13181, and rs2228001) in DNA repair genes (XPC, XRCC4, XRCC1, XRCC4, XPD, XRCC7, and XRCC3) interacted with AFB1, and the gene-environmental interactive role in the risk of HCC using hospital-based case-control study (including 1486 HCC cases and 1996 controls). Genotypes of DNA repair genes were tested using TaqMan-PCR technique. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 2.08 for medium AFB1 exposure level and OR = 6.52 for high AFB1 exposure level]. Increasing risk of HCC was also observed in these with the mutants of DNA repair genes (risk values were from 1.57 to 5.86). Furthermore, these risk roles would be more noticeable under the conditions of two variables, and positive interactive effects were proved in the followed multiplicative interaction analysis. These results suggested that DNA repair risk genotypes might interact with AFB1 in the risk of HCC.

Unlabelled: Genetic polymorphisms in DNA repair genes may influence individual variations in DNA repair capacity, and this may be associated with the risk and outcome of hepatocellular carcinoma (HCC) related to aflatoxin B1 (AFB1) exposure. In this study, we focused on the polymorphism of xeroderma pigmentosum complementation group C (XPC) codon 939 (rs#2228001), which is involved in nucleotide excision repair. We conducted a case-control study including 1156 HCC cases and 1402 controls without any evidence of hepatic disease to evaluate the associations between this polymorphism and HCC risk and prognosis in the Guangxi population. AFB1 DNA adduct levels, XPC genotypes, and XPC protein levels were tested with a comparative enzyme-linked immunosorbent assay, TaqMan polymerase chain reaction for XPC genotypes, and immunohistochemistry, respectively. Higher AFB1 exposure was observed among HCC patients versus the control group [odds ratio (OR) = 9.88 for AFB1 exposure years and OR = 6.58 for AFB1 exposure levels]. The XPC codon 939 Gln alleles significantly increased HCC risk [OR = 1.25 (95% confidence interval = 1.03-1.52) for heterozygotes of the XPC codon 939 Lys and Gln alleles (XPC-LG) and OR = 1.81 (95% confidence interval = 1.36-2.40) for homozygotes of the XPC codon 939 Gln alleles (XPC-GG)]. Significant interactive effects between genotypes and AFB1 exposure status were also observed in the joint-effects analysis. This polymorphism, moreover, was correlated with XPC expression levels in cancerous tissues (r = -0.369, P < 0.001) and with the overall survival of HCC patients (the median survival times were 30, 25, and 19 months for patients with homozygotes of the XPC codon 939 Lys alleles, XPC-LG, and XPC-GG, respectively), especially under high AFB1 exposure conditions. Like AFB1 exposure, the XPC codon 939 polymorphism was an independent prognostic factor influencing the survival of HCC. Additionally, this polymorphism multiplicatively interacted with the xeroderma pigmentosum complementation group D codon 751 polymorphism with respect to HCC risk (OR(interaction) = 1.71)., Conclusion: These results suggest that the XPC codon 939 polymorphism may be associated with the risk and outcome of AFB1-related HCC in the Guangxi population and may interact with AFB1 exposure in the process of HCC induction by AFB1.

Genetic polymorphisms in DNA repair genes may influence individual variation in DNA repair capacity, which may be associated with risk of gastric antrum adenocarcinoma (GAA) related to Helicobacter pylori infection. This study, including 361 GAAs and 616 controls without any evidence of tumors, was designed to evaluate the association between the polymorphisms of DNA repair genes XPC Ala499Val (RS#2228000) and Lys939Gln (RS#2228001), XPD Lys751Gln (RS#13181), and XRCC4 Ala247Ser (RS#3734091) and Ser298Asn (RS#1805377), and GAA risk for Guangxi population by means of TaqMan-PCR analysis. Increased risks of GAA were found for individuals with H. pylori positive [odds ratio (OR), 2.48; 95% confidence interval (CI), 1.84-3.33] or cagA positive (OR, 7.34; 95% CI, 5.46-9.87). No differences were observed among the studied groups with regard to the genotype distribution of XPC codons 499 and 939 and of XRCC4 codon 247; but XPD codon 751 genotypes with Gln [ORs (95% CI) were 2.67 (1.98-3.58) and 3.97 (2.64-5.99) for Lys/Gln and Gln/Gln, respectively] and XRCC4 codon 298 genotypes with Asn [ORs (95% CI) were 3.01 (2.21-4.10) and 4.78 (3.24-7.05) for Ser/Asn and Asn/Asn, respectively] increased the risk of GAA. Interestingly, there was an interactive effect between the risk genotypes of these two genes and cagA-positive status in the GAA risk (OR(interact) = 2.05 and 2.08, respectively). However, we did not find the gene-H. pylori-status interaction effects on the risk of GAA (P(interact) > 0.05). The results suggested that the polymorphisms of XPD codon 751 and XRCC4 codon 298 are associated with an increased risk of developing H. pylori-related GAA among Guangxi population., ((c) 2010 Wiley-Liss, Inc.)

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.

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.

Objective: To study the association between susceptibility to aflatoxin B1 (AFB1)-related hepatocellular carcinoma(HCC) and the null genotypes of detoxication gene gstM1 and gstT1., Methods: Peripheral blood white blood cells DNA samples were obtained from all the subjects including 140 HCC cases and 536 controls from AFB1 high risk area Guangxi. gstM1 and gstT1 polymorphisms were detected by polymerase chain reaction technique., Results: (1) gstM1- and gstT1-present were associated with decreasing risk of HCC. gstM1- and gstT1-null were associated with the increasing risk of HCC [adjusted OR (95 % CI) = 2.07 (1.20-3.57) and 1.44 (0.85-2.45), respectively]; (2) The appearance of both gstM1- and gstT1-null genotypes were more susceptible to HCC than either one of them(adjusted OR and 95% CI are 2.43 and (1.19-4.97); (3) From low/median to high level of AFB1 exposure, both gstM1- and gstTl-null genotypes were associated with significantly conspicuous increasing risk of HCC [adjusted OR(95% CI) = 12.76(5.38-30.24) and 7.82(3.61-16.90) respectively]., Conclusion: It was suggested that: genetic polymorphisms of gstM1 and gstT1 were susceptible to HCC; individuals who were gstM1- or gstT1-null would have an increasing risk of developing HCC while individuals with both nulls were more susceptible. There was evidence of interaction between gstM1- and gstT1-null and the level of AFB1 exposure which was associated with the increasing risk of HCC.