Engels Eric A, Wu Xifeng, Gu Jian, Dong Qiong, Liu Jun, Spitz Margaret R
Viral Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland 20892, USA.
Cancer Res. 2007 Jul 1;67(13):6520-7. doi: 10.1158/0008-5472.CAN-07-0370. Epub 2007 Jun 27.
Inflammatory responses to environmental exposures, such as tobacco smoke, may play a role in lung carcinogenesis. To test this hypothesis, we studied genetic polymorphisms in the inflammation pathway in relation to lung cancer risk. We evaluated a panel of 59 single nucleotide polymorphisms (SNP) in 37 inflammation-related genes among non-Hispanic Caucasian lung cancer cases (N=1,553) and controls (N=1,730) from Houston, Texas. Logistic regression was used to assess associations with lung cancer under a dominant genetic model adjusted for sex, age, and smoking. Haplotypes were estimated with the expectation-maximization algorithm. False-positive report probabilities (FPRP) were calculated for significant associations. Interleukin 1 beta (IL1B) C3954T was associated with lung cancer [odds ratio (OR), 1.27; 95% confidence interval (95% CI), 1.10-1.47; FPRP 0.148]. Two IL1A SNPs (C-889T and Ala(114)Ser) were also related to lung cancer (OR, 1.18-1.22), although FPRPs were higher. One IL1A-IL1B haplotype, containing only the IL1B 3954T allele, was associated with elevated lung cancer risk (OR, 1.80; 95% CI, 1.24-2.61). These associations were stronger in heavy smokers, particularly for IL1B C3954T (OR, 1.59; 95% CI, 1.28-1.97; FPRP 0.004). Lung cancer risk was unrelated to polymorphisms in IL1 receptor or antagonist genes. Associations with lung cancer were also seen for SNPs in granulocyte macrophage colony stimulating factor and peroxisome proliferator-activated factor-delta, but FPRPs were high. IL1A and IL1B polymorphisms are associated with increased lung cancer risk, especially among heavy smokers. IL1A and IL1B are critical signals in initiating inflammation. Our results suggest that a dysregulated inflammatory response to tobacco-induced lung damage promotes carcinogenesis.
对环境暴露（如烟草烟雾）的炎症反应可能在肺癌发生过程中起作用。为验证这一假设，我们研究了炎症途径中的基因多态性与肺癌风险的关系。我们评估了来自得克萨斯州休斯顿的非西班牙裔白人肺癌病例（N = 1553）和对照（N = 1730）中37个炎症相关基因的59个单核苷酸多态性（SNP）。采用逻辑回归在调整了性别、年龄和吸烟因素的显性遗传模型下评估与肺癌的关联。用期望最大化算法估计单倍型。计算显著关联的假阳性报告概率（FPRP）。白细胞介素1β（IL1B）C3954T与肺癌相关[比值比（OR），1.27；95%置信区间（95%CI），1.10 - 1.47；FPRP 0.148]。两个IL1A SNP（C - 889T和Ala(114)Ser）也与肺癌有关（OR，1.18 - 1.22），尽管FPRP较高。一种仅包含IL1B 3954T等位基因的IL1A - IL1B单倍型与肺癌风险升高相关（OR，1.80；95%CI，1.24 - 2.61）。这些关联在重度吸烟者中更强，尤其是IL1B C3954T（OR，1.59；95%CI，1.28 - 1.97；FPRP 0.004）。肺癌风险与IL1受体或拮抗剂基因的多态性无关。粒细胞巨噬细胞集落刺激因子和过氧化物酶体增殖物激活因子 - δ中的SNP也与肺癌有关，但FPRP较高。IL1A和IL1B多态性与肺癌风险增加相关，尤其是在重度吸烟者中。IL1A和IL1B是引发炎症的关键信号。我们的结果表明，对烟草诱导的肺损伤的炎症反应失调促进了癌症发生。
