XRCC1、XRCC3和XPD基因多态性与结直肠癌风险：台湾的一项病例对照研究
Polymorphisms of the XRCC1, XRCC3, & XPD genes, and colorectal cancer risk: a case-control study in Taiwan.
作者信息
Yeh Chih-Ching, Sung Fung-Chang, Tang Reiping, Chang-Chieh Chung Rong, Hsieh Ling-Ling
机构信息
Institute of Environmental Health, National Taiwan University College of Public Health, Taipei 100, Taiwan.
出版信息
BMC Cancer. 2005 Jan 28;5:12. doi: 10.1186/1471-2407-5-12.
BACKGROUND
Recent studies relating to the association between DNA repair-gene polymorphisms and colorectal cancer risk would, to the best of our knowledge, appear to be very limited. This study was designed to examine the polymorphisms associated with three DNA repair genes, namely: XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln, and investigate their role as susceptibility markers for colorectal cancer.
METHODS
We conducted a case-control study including 727 cases of cancer and 736 hospital-based age- and sex-matched healthy controls to examine the role of genetic polymorphisms of three DNA-repair genes (XRCC1, XRCC3 and XPD) in the context of colorectal cancer risk for the Taiwanese population. Genomic DNA isolated from 10 ml whole blood was used to genotype XRCC1 Arg399Gln, XRCC3 Thr241Met and XPD Lys751Gln by means of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis.
RESULTS
The risk for colorectal cancer did not appear to differ significantly amongst individuals featuring the XRCC1 399Arg/Arg genotype (OR = 1.18; 95% CI, 0.96-1.45), the XRCC3 241Thr/Thr genotype (OR = 1.25; 95% CI, 0.88-1.79) or the XPD 751Gln allele (OR = 1.20; 95% CI, 0.90-1.61), although individuals featuring a greater number of risk genotypes (genotype with OR greater than 1) did experience a higher risk for colorectal cancer when compared to those who didn't feature any risk genotypes (Trend test P = 0.03). Compared with those individuals who didn't express any putative risk genotypes, individuals featuring all of the putative risk genotypes did experience a significantly greater cancer risk (OR = 2.43, 95% CI = 1.21-4.90), particularly for individuals suffering tumors located in the rectum (OR = 3.18, 95% CI = 1.29-7.82) and diagnosed prior to the age of 60 years (OR = 4.90, 95% CI = 1.72-14.0).
CONCLUSIONS
Our results suggest that DNA-repair pathways may simultaneously modulate the risk of colorectal cancer for the Taiwanese population, and, particularly for rectal cancer and younger patients.
背景
就我们所知，近期有关DNA修复基因多态性与结直肠癌风险之间关联的研究似乎非常有限。本研究旨在检测与三个DNA修复基因相关的多态性，即：X射线修复交叉互补蛋白1（XRCC1）基因的精氨酸399位点突变为谷氨酰胺（Arg399Gln）、X射线修复交叉互补蛋白3（XRCC3）基因的苏氨酸241位点突变为甲硫氨酸（Thr241Met）以及XPD基因的赖氨酸751位点突变为谷氨酰胺（Lys751Gln），并探究它们作为结直肠癌易感性标志物的作用。
方法
我们开展了一项病例对照研究，纳入727例癌症患者和736例基于医院的年龄及性别匹配的健康对照，以研究三个DNA修复基因（XRCC1、XRCC3和XPD）的基因多态性在台湾人群结直肠癌风险中的作用。从10毫升全血中分离的基因组DNA用于通过聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）分析对XRCC1 Arg399Gln、XRCC3 Thr241Met和XPD Lys751Gln进行基因分型。
结果
具有XRCC1基因399精氨酸/精氨酸（399Arg/Arg）基因型（比值比[OR]=1.18；95%置信区间[CI]，0.96 - 1.45）、XRCC3基因241苏氨酸/苏氨酸（241Thr/Thr）基因型（OR = 1.25；95% CI，0.88 - 1.79）或XPD基因751谷氨酰胺（751Gln）等位基因的个体，其患结直肠癌的风险似乎无显著差异（OR = 1.20；95% CI，0.90 - 1.61），不过与未携带任何风险基因型的个体相比，携带更多风险基因型（OR大于1的基因型）的个体患结直肠癌的风险确实更高（趋势检验P = 0.03）。与未表达任何假定风险基因型的个体相比，具有所有假定风险基因型的个体患癌风险显著更高（OR = 2.43，95% CI = 1.21 - 4.90），尤其是对于患有直肠肿瘤的个体（OR = 3.18，95% CI = 1.29 - 7.82）以及60岁之前被诊断出的个体（OR = 4.90，95% CI = 1.72 - 14.0）。
结论
我们的结果表明，DNA修复途径可能同时调节台湾人群患结直肠癌的风险，尤其是直肠癌和年轻患者。
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