The Association of APEX1 and OGG1 Gene Polymorphisms with DNA Damage Response inHuman Colorectal Cancer
Objective To investigate the correlation between APEX1 and OGG1 gene polymorphisms and DNA damage response in human colorectal cancer.Methods A total of 240 patients with colorectal cancer who were hospitalized in the Department of Gastrointestinal Surgery and Oncology of Provincial People's Hospital from March,2020 to December,2022 were recruited as study subjects.All colorectal cancer patients were pathologically confirmed.A total of 300 healthy volunteers who underwent physical examination in our hospital during the same period were recruited as controls.Each subject received informed consent.Clinical information of cases and volunteers was obtained from pathology archives and questionnaires.The genotype and allele frequencies of the control population were predicted by Hardy-Weinberg equilibrium law.The genotype distribution and odds ratio of all colorectal cancer cases and control participants were analyzed.The interaction between polymorphism and smoking confounders was analyzed with a logistic regression model.Individuals with more than one variant allele were analyzed for colorectal cancer risk by calculating adjusted OR values for specific combinations.Results There were no significant differences in age,sex distribution,smoking status and family history of cancer between the two groups(P＞0.05).The frequencies of all genotypes in the control group were consistent with those predicted by Hardy-Weinberg(P＞0.05).The results showed that the risk of colorectal cancer in XRCC1 399Gln/Gln individuals and Arg/Gln genotypes was significantly higher than that in wild-type Arg/Arg genotypes.The mutant alleles of OGG1326Cys and APE1 148Glu showed deleterious effects with OR of 1.23 and 1.66,respectively.For homozygous individuals with APE1-141G/G variant allele,a slightly reduced OR(OR=0.58,95％CI 1.73-2.14,P=0.08)was obtained,suggesting that the allele could reduce the risk of colorectal cancer,while there was no significant difference(P＞0.05).In addition,there were no significant differences in the genotype or allele distributions of OGG1 Ser326Cys and APE1 Asp148Glu between case and control groups(P＞0.05).For APE1-141T/G polymorphism,a significant protective effect was observed against current smokers of the GG genotype using the homozygous TT genotype as the reference group(OR=0.39,95％CI 0.16-0.88;P=0.04),but no such protective effect was found in non-smokers.XRCC1 399Arg/Gln showed harmful effect,with OR=1.66,while the difference was not statistically significant(P＞0.05).Conclusion This study investigated the relationship between polymorphisms of DNA base excision repair genes(XRCC1,OGG1,and APE1)and the risk of colorectal cancer.We show that several gene variants can significantly increase the risk of colorectal cancer,but APe1-141g/G may reduce the risk of colorectal cancer in current smokers.
APEX1OGG1XRCC1Gene polymorphismColorectal cancer
陈翼霖、曹辉彩、贺世畅、高艳、王敏、ZHANG Qian
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保定市第一中心医院医学检验二科,河北保定 071000
Second Department of Medical Laboratory,Baoding City First Central Hospital,Baoding 071000,China
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