Vogel Ulla, Christensen Jane, Wallin Håkan, Friis Søren, Nexø Bjørn A, Raaschou-Nielsen Ole, Overvad Kim, Tjønneland Anne
National Research Centre for the Working Environment, DK-2100 Copenhagen O, Denmark.
Mutat Res. 2008 Mar 1;639(1-2):89-100. doi: 10.1016/j.mrfmmm.2007.11.004. Epub 2007 Nov 26.
Lung cancer risk was investigated in relation to single nucleotide polymorphisms in genes involved in the inflammatory response. The aim was to see if polymorphisms modifying the inflammatory response are associated with risk of lung cancer and if there were interactions between the same polymorphism and factors, which modify an inflammatory response, such as smoking status, duration, and intensity, and use of NSAID. The functional SNPs IL-1B T-31C, IL6 G-174C, IL8 T-251A, IL10 C-592T, COX2 C8473T, COX2 A-1195G and PPARgamma2 Pro(12)Ala were included. A case-cohort study including 428 lung cancer cases and a sub-cohort of 800 persons was nested within a population-based prospective study of 57,053 individuals. Variant allele carriers of IL-1B T-31C were at increased risk of lung cancer (IRR=1.51, 95% CI=1.08-2.12). There was interaction between the polymorphism COX-2 T8473C and smoking status. Thus, non-smoking variant allele carriers were at 5.75-fold (95% CI=1.25-26.43) higher risk of lung cancer than for homozygous wild type allele carriers. Lung cancer risk was similar for all genotype carriers among past and current smokers. There were, however, very few non-smoking lung cancer cases. There was interaction between IL-1B T-31C, COX-2 A-1195G and PPARgamma2 Pro(12)Ala and NSAID use in relation to lung cancer risk. For the two latter, NSAID use was only associated with a lower cancer risk among homozygous wild type allele carriers. p for interaction was 3 x 10(-6) for COX-2 A-1195G and 9 x 10(-5) for PPARgamma2 Pro(12)Ala. The results suggest that NSAID use may modify risk of lung cancer differently depending on the genotype.
研究了肺癌风险与炎症反应相关基因中的单核苷酸多态性之间的关系。目的是确定改变炎症反应的多态性是否与肺癌风险相关，以及同一多态性与改变炎症反应的因素（如吸烟状况、持续时间和强度以及非甾体抗炎药的使用）之间是否存在相互作用。纳入了功能性单核苷酸多态性IL-1B T-31C、IL6 G-174C、IL8 T-251A、IL10 C-592T、COX2 C8473T、COX2 A-1195G和PPARγ2 Pro(12)Ala。一项包含428例肺癌病例和800人亚队列的病例队列研究嵌套在一项对57,053名个体进行的基于人群的前瞻性研究中。IL-1B T-31C的变异等位基因携带者患肺癌的风险增加（发病率比值比=1.51，95%可信区间=1.08-2.12）。COX-2 T8473C多态性与吸烟状况之间存在相互作用。因此，非吸烟变异等位基因携带者患肺癌的风险比纯合野生型等位基因携带者高5.75倍（95%可信区间=1.25-26.43）。既往吸烟者和当前吸烟者中，所有基因型携带者的肺癌风险相似。然而，非吸烟肺癌病例很少。IL-1B T-31C、COX-2 A-1195G和PPARγ2 Pro(12)Ala与非甾体抗炎药的使用在肺癌风险方面存在相互作用。对于后两者，仅在纯合野生型等位基因携带者中，使用非甾体抗炎药与较低的癌症风险相关。COX-2 A-1195G的相互作用p值为3×10⁻⁶，PPARγ2 Pro(12)Ala的相互作用p值为9×10⁻⁵。结果表明，根据基因型不同，使用非甾体抗炎药可能会对肺癌风险产生不同的影响。
