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Abstract：
OBJECTIVE: Gastrointestinal (GI) cancer presents a significant worldwide health burden, influenced by a combination of genetic and environmental factors. This study endeavors to explore the combined effects of the XRCC1, XRCC2, XRCC3, and TP53 genes that contribute to the heightened risk of GI cancer, shedding light on their combined influence on cancer susceptibility.
METHODS: A total of 200 histologically confirmed cases of GI cancer and an equal number of controls were selected to examine genetic polymorphisms within the XRCC1, XRCC2, XRCC3, and TP53 genes using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association of these polymorphisms with GI cancer susceptibility, with statistical significance (p ≤ 0.05).
RESULTS: Logistic regression analysis confirmed strong evidence of synergistic interactions among specific variant genotypes. Notably, combinations such as heterozygous Arg/Ser+Ser/Ser genotype of TP53 Arg249Ser polymorphism with Arg/Trp+Trp/Trp genotype of XRCC1 Arg194Trp polymorphism (OR=2.64; 95% CI: 1.35-5.18; p=0.004), Arg/Gln+Gln/Gln genotype of XRCC1 at codon 399 (OR=5.04; 95% CI: 2.81-9.05; p=0.0001), Arg/His and His/His genotypes of XRCC2 Arg188His (OR=2.16; 95% CI: 1.06-4.39; p<0.032), and Thr/Met+Met/Met genotype of XRCC3 Thr242Met (OR=3.48; 95% CI: 1.79-6.77; p=0.0002) showed significant associations with GI cancer risk in the study population.
CONCLUSIONS: The findings indicate a notable association between the combined effect of heterozygous variant genotypes of TP53 and variant genotypes of XRCC1, XRCC2, and XRCC3 on GI cancer risk. However, further research with a larger sample size and broad single nucleotide polymorphism (SNP) spectra is necessary to understand the interaction between genetic variations and environmental factors influencing GI cancer susceptibility.
METHODS: A total of 200 histologically confirmed cases of GI cancer and an equal number of controls were selected to examine genetic polymorphisms within the XRCC1, XRCC2, XRCC3, and TP53 genes using the polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) with 95% confidence intervals (CI) were calculated to assess the association of these polymorphisms with GI cancer susceptibility, with statistical significance (p ≤ 0.05).
RESULTS: Logistic regression analysis confirmed strong evidence of synergistic interactions among specific variant genotypes. Notably, combinations such as heterozygous Arg/Ser+Ser/Ser genotype of TP53 Arg249Ser polymorphism with Arg/Trp+Trp/Trp genotype of XRCC1 Arg194Trp polymorphism (OR=2.64; 95% CI: 1.35-5.18; p=0.004), Arg/Gln+Gln/Gln genotype of XRCC1 at codon 399 (OR=5.04; 95% CI: 2.81-9.05; p=0.0001), Arg/His and His/His genotypes of XRCC2 Arg188His (OR=2.16; 95% CI: 1.06-4.39; p<0.032), and Thr/Met+Met/Met genotype of XRCC3 Thr242Met (OR=3.48; 95% CI: 1.79-6.77; p=0.0002) showed significant associations with GI cancer risk in the study population.
CONCLUSIONS: The findings indicate a notable association between the combined effect of heterozygous variant genotypes of TP53 and variant genotypes of XRCC1, XRCC2, and XRCC3 on GI cancer risk. However, further research with a larger sample size and broad single nucleotide polymorphism (SNP) spectra is necessary to understand the interaction between genetic variations and environmental factors influencing GI cancer susceptibility.
摘要：
目的：胃肠道（GI）癌症在全球范围内带来了巨大的健康负担，受遗传和环境因素的综合影响。这项研究试图探索XRCC1，XRCC2，XRCC3和TP53基因的联合作用，这些基因有助于增加胃肠道癌症的风险。阐明它们对癌症易感性的综合影响。
方法：选择了200例经组织学证实的胃肠道癌病例和相同数量的对照，使用基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）检查XRCC1，XRCC2，XRCC3和TP53基因内的遗传多态性。计算比值比（OR）和95％置信区间（CI）以评估这些多态性与胃肠道癌症易感性的关联。具有统计学意义(p≤0.05)。
结果：Logistic回归分析证实了特定变异基因型之间的协同相互作用的有力证据。值得注意的是,TP53Arg249Ser多态性的杂合Arg/Ser/Ser基因型与XRCC1Arg194Trp多态性的Arg/Trp/Trp基因型等组合（OR=2.64；95％CI：1.35-5.18；p=0.004），密码子399处XRCC1的Arg/Gln+Gln/Gln基因型(OR=5.04;95%CI:2.81-9.05;p=0.0001),XRCC2Arg188His的Arg/His和His/His基因型（OR=2.16；95％CI：1.06-4.39；p<0.032），在研究人群中,XRCC3Thr242Met的Thr/Met+Met/Met基因型(OR=3.48;95%CI:1.79-6.77;p=0.0002)与GI癌症风险显著相关。
结论：研究结果表明，TP53杂合变异基因型与XRCC1、XRCC2和XRCC3变异基因型的联合作用对胃肠道癌症风险有显著关联。然而,有必要进一步研究更大的样本量和广泛的单核苷酸多态性（SNP）谱，以了解遗传变异和影响胃肠道癌症易感性的环境因素之间的相互作用。
方法：选择了200例经组织学证实的胃肠道癌病例和相同数量的对照，使用基于聚合酶链反应的限制性片段长度多态性（PCR-RFLP）检查XRCC1，XRCC2，XRCC3和TP53基因内的遗传多态性。计算比值比（OR）和95％置信区间（CI）以评估这些多态性与胃肠道癌症易感性的关联。具有统计学意义(p≤0.05)。
结果：Logistic回归分析证实了特定变异基因型之间的协同相互作用的有力证据。值得注意的是,TP53Arg249Ser多态性的杂合Arg/Ser/Ser基因型与XRCC1Arg194Trp多态性的Arg/Trp/Trp基因型等组合（OR=2.64；95％CI：1.35-5.18；p=0.004），密码子399处XRCC1的Arg/Gln+Gln/Gln基因型(OR=5.04;95%CI:2.81-9.05;p=0.0001),XRCC2Arg188His的Arg/His和His/His基因型（OR=2.16；95％CI：1.06-4.39；p<0.032），在研究人群中,XRCC3Thr242Met的Thr/Met+Met/Met基因型(OR=3.48;95%CI:1.79-6.77;p=0.0002)与GI癌症风险显著相关。
结论：研究结果表明，TP53杂合变异基因型与XRCC1、XRCC2和XRCC3变异基因型的联合作用对胃肠道癌症风险有显著关联。然而,有必要进一步研究更大的样本量和广泛的单核苷酸多态性（SNP）谱，以了解遗传变异和影响胃肠道癌症易感性的环境因素之间的相互作用。
