Vineis P, Veglia F, Garte S, Malaveille C, Matullo G, Dunning A, Peluso M, Airoldi L, Overvad K, Raaschou-Nielsen O, Clavel-Chapelon F, Linseisen J P, Kaaks R, Boeing H, Trichopoulou A, Palli D, Crosignani P, Tumino R, Panico S, Bueno-De-Mesquita H B, Peeters P H, Lund E, Gonzalez C A, Martinez C, Dorronsoro M, Barricarte A, Navarro C, Quiros J R, Berglund G, Jarvholm B, Day N E, Key T J, Saracci R, Riboli E, Autrup H
Imperial College London, London, UK.
Ann Oncol. 2007 Jul;18(7):1230-42. doi: 10.1093/annonc/mdm109. Epub 2007 May 11.
We chose a set of candidate single nucleotide polymorphisms (SNPs) to investigate gene-environment interactions in three types of cancer that have been related to air pollution (lung, bladder and myeloid leukemia).
The study has been conducted as a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort (409 cancer cases and 757 matched controls). We included never and ex-smokers. SNPs were in genes involved in oxidative stress, phase I metabolizing genes, phase II metabolizing genes and methylenetetrahydrofolate reductase (MTHFR).
The most notable findings are: GSTM1 deletion and bladder cancer risk [odds ratio (OR) = 1.60; 95% confidence interval 1.00-2.56]; CYP1A1 and leukemia (2.22, 1.33-3.70; heterozygotes); CYP1B1 and leukemia (0.47, 0.27-0.84; homozygotes); MnSOD and leukemia (1.91, 1.08-3.38; homozygotes) and NQO1 and lung cancer (8.03, 1.73-37.3; homozygotes). Other statistically significant associations were found in subgroups defined by smoking habits (never or ex-smokers), environmental tobacco smoke or gender, with no obvious pattern. When gene variants were organized according to the three main pathways, the emerging picture was of a strong involvement of combined phase I enzymes in leukemia, with an OR of 5 (1.63-15.4) for those having three or more variant alleles. The association was considerably stronger for leukemias arising before the age of 55.
我们选择了一组单核苷酸多态性（SNP）候选基因，以研究与空气污染相关的三种癌症（肺癌、膀胱癌和髓系白血病）中的基因-环境相互作用。
该研究作为一项巢式病例对照研究，在欧洲癌症与营养前瞻性调查队列中进行（409例癌症病例和757例匹配对照）。我们纳入了从不吸烟者和已戒烟者。SNP位于参与氧化应激的基因、I相代谢基因、II相代谢基因和亚甲基四氢叶酸还原酶（MTHFR）中。
最显著的发现是：GSTM1基因缺失与膀胱癌风险[比值比（OR）=1.60；95%置信区间1.00 - 2.56]；CYP1A1与白血病（2.22，1.33 - 3.70；杂合子）；CYP1B1与白血病（0.47，0.27 - 0.84；纯合子）；MnSOD与白血病（1.91，1.08 - 3.38；纯合子）以及NQO1与肺癌（8.03，1.73 - 37.3；纯合子）。在根据吸烟习惯（从不吸烟或已戒烟者）、环境烟草烟雾或性别定义的亚组中发现了其他具有统计学意义的关联，但无明显模式。当根据三种主要途径对基因变异进行分类时，新出现的情况是I相酶联合作用在白血病中起重要作用，对于具有三个或更多变异等位基因的个体，OR为5（1.63 - 15.4）。对于55岁之前发生的白血病，这种关联要强得多。
