Chao Chun, Zhang Zuo-Feng, Berthiller Julien, Boffetta Paolo, Hashibe Mia
Gene-Environment Epidemiology Group, IARC, 150, cours Albert Thomas, 69372 Lyon Cedex 08, France.
Cancer Epidemiol Biomarkers Prev. 2006 May;15(5):979-87. doi: 10.1158/1055-9965.EPI-05-0899.
NAD(P)H:quinone oxidoreductase 1 (NQO1) is a cytosolic enzyme that catalyzes the two-electron reduction of quinoid compounds into hydroquinones, their less toxic form. A sequence variant at position 609 (C --> T) in the NQO1 gene encodes an enzyme with reduced quinone reductase activity in vitro and thus was hypothesized to affect cancer susceptibility. We conducted meta-analyses focusing on three cancer sites (lung, bladder, and colorectum) to summarize the findings from the current literature and to explore sources of heterogeneity.
There is no clear association between the NQO1 Pro187Ser polymorphism and lung cancer risk in the three ethnic groups examined: odds ratio (OR(White)) C/T + T/T versus C/C = 1.04 [95% confidence interval (95% CI), 0.96-1.13], OR(Asian) = 0.99 (95% CI, 0.72-1.34), and OR(Blacks) = 0.95 (95% CI, 0.66-1.36). However, a modestly increased risk was suggested for the variant homozygotes in whites (OR T/T versus C/C, 1.19; 95% CI, 0.94-1.50). Analysis excluding one outlier study suggested the variant allele may be associated with reduced lung cancer risk in Asians. Meta-analyses for bladder and colorectal cancer suggested a statistically significant association with the variant genotypes in whites. In stratified analyses, the NQO1 Pro187Ser variant genotypes were associated with slightly increased lung cancer risk in white ever smokers but not in white never smokers and were mainly associated with a reduced risk of lung adenocarcinoma but not squamous cell carcinoma in Asians.
Results from our meta-analyses suggest that the variant NQO1 Pro187Ser genotype may affect individual susceptibility to lung, bladder, and colorectal cancer. Such effects of the NQO1 polymorphism seem to be modified by ethnicity and smoking status.
NAD(P)H：醌氧化还原酶1（NQO1）是一种胞质酶，可催化醌类化合物两电子还原为毒性较低的对苯二酚形式。NQO1基因第609位（C→T）的序列变异在体外编码一种醌还原酶活性降低的酶，因此推测该变异会影响癌症易感性。我们进行了荟萃分析，重点关注三个癌症部位（肺癌、膀胱癌和结直肠癌），以总结当前文献的研究结果并探索异质性来源。
在所研究的三个种族群体中，NQO1 Pro187Ser多态性与肺癌风险之间没有明确关联：比值比（白人的OR(White)）C/T + T/T与C/C相比 = 1.04 [95%置信区间（95%CI），0.96 - 1.13]，亚洲人的OR(Asian) = 0.99（95%CI，0.72 - 1.34），黑人的OR(Blacks) = 0.95（95%CI，0.66 - 1.36）。然而，白人中该变异纯合子的风险有适度增加（OR T/T与C/C相比，1.19；95%CI，0.94 - 1.50）。排除一项异常值研究后的分析表明，该变异等位基因可能与亚洲人肺癌风险降低有关。膀胱癌和结直肠癌的荟萃分析表明，白人中该变异基因型与癌症存在统计学显著关联。在分层分析中，NQO1 Pro187Ser变异基因型与白人曾经吸烟者的肺癌风险略有增加相关，但与白人从不吸烟者无关，并且在亚洲人中主要与肺腺癌风险降低相关，而与鳞状细胞癌无关。
我们的荟萃分析结果表明，变异的NQO1 Pro187Ser基因型可能影响个体对肺癌、膀胱癌和结直肠癌的易感性。NQO1多态性的这种影响似乎因种族和吸烟状况而异。
