XRCC1, XRCC3, and XPD polymorphisms as modifiers of the effect of smoking and alcohol on colorectal adenoma risk
XRCC1, XRCC3, and XPD polymorphisms as modifiers of the effect of smoking and alcohol on colorectal adenoma risk
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DOI：
10.1158/1055-9965.epi-06-0381
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发表时间：
2006-12-01
影响因子：
3.8
通讯作者：
Haile, Robert W.
中科院分区：
文献类型：
--
作者：
Stern, Mariana C.;Siegmund, Kimberly D.;Haile, Robert W.
我们在洛杉矶县进行了一项基于乙状结肠镜检查的病例对照研究（753例，799例对照），研究了三种DNA修复基因XRCC 1（Arg 194 Trp和Arg 399 Gln）、XRCC 3（Thr 241 Met）和XPD（Lys 751 Gln）单核苷酸多态性（SNP）在酒精和吸烟影响中的潜在修饰作用。我们以前曾报道过XRCC 1密码子399 SNP与这些受试者的腺瘤风险之间存在负相关。我们现在报告，与Lys/Lys和Lys/Gln基因型组合的受试者相比，XPD Gln/Gln基因型受试者与腺瘤风险呈负相关[比值比（OR），0.7; 95%置信区间（95%CI），0.5-1.0]。这种关联在不同种族之间存在差异（基因×种族异质性似然比检验，P=0.009），拉丁美洲人（OR，0.1; 95%CI，0.01-0.5）的负相关性比非拉丁美洲人（OR，0.9; 95%CI，0.4.3）更强。我们没有发现XRCC 3 x吸烟或酒精相互作用或XRCC 1 x酒精相互作用的证据。相反，我们的数据支持XRCC 1吸烟相互作用（P=0.048）。虽然XPD没有改变吸烟的影响，但我们的数据表明XPD x酒精相互作用。忽略XPD的分析显示酒精摄入量和腺瘤患病率之间没有关联;然而，在密码子751 Gln/Gln基因型携带者中，我们发现了显著的正相关性（OR，2.5; 95%CI，1.2-5.2，饮酒者;交互作用检验P=0.04）。我们的数据表明，吸烟和饮酒的影响可能会有所不同，这取决于参与碱基切除修复和核苷酸切除修复途径的蛋白质的遗传背景。
Using a sigmoidoscopy-based case-control study (753 cases, 799 controls) in Los Angeles County, we investigated the potential modifier role in the effect of alcohol and smoking of single-nucleotide polymorphisms (SNP) in three DNA repair genes, XRCC1 (Arg194Trp and Arg399Gln), XRCC3 (Thr241Met), and XPD (Lys751Gln). We have previously reported an inverse association between the XRCC1 codon 399 SNP and adenoma risk among these subjects. We now report that subjects with the XPD Gln/Gln genotype were inversely associated with adenoma risk [odds ratio (OR), 0.7; 95% confidence interval (95% CI), 0.5-1.0] when compared with subjects with the Lys/Lys and Lys/Gln genotypes combined. This association differed between different ethnic groups (gene x race heterogeneity likelihood ratio test, P=0.009), with a stronger inverse association among Latinos (OR, 0.1; 95% Cl, 0.01-0.5) than among non-Latinos (OR, 0.9; 95% Cl, 0.4.3). We found no evidence of an XRCC3 x smoking or alcohol interaction or an XRCC1 x alcohol interaction. Instead, our data supported an XRCC1 smoking interaction (P=0.048). Whereas XPD did not modify the effect of smoking, our data suggested an XPD x alcohol interaction. Analyses ignoring XPD showed no association between alcohol intake and adenoma prevalence; however, among carriers of the codon 751 Gln/Gln genotype, we found a significant positive association (OR, 2.5; 95% CI, 1.2-5.2 for ever drinkers; test of interaction P=0.04). Our data suggest that the effects of smoking and alcohol may vary depending on the genetic background of proteins that participate in the base excision repair and nucleotide excision repair pathways.