Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
Department of Medicine, University of Washington, Seattle, Washington.
J Thorac Oncol. 2018 May;13(5):649-659. doi: 10.1016/j.jtho.2018.01.022. Epub 2018 Mar 23.
Chronic inflammation has been implicated in carcinogenesis, with increasing evidence of its role in lung cancer. We aimed to evaluate the role of genetic polymorphisms in inflammation-related genes in the risk for development of lung cancer.
A nested case-control study design was used, and 625 cases and 625 well-matched controls were selected from participants in the β-Carotene and Retinol Efficacy Trial, which is a large, prospective lung cancer chemoprevention trial. The association between lung cancer incidence and survival and 23 polymorphisms descriptive of 11 inflammation-related genes (interferon gamma gene [IFNG], interleukin 10 gene [IL10], interleukin 1 alpha gene [IL1A], interleukin 1 beta gene [IL1B], interleukin 2 gene [IL2], interleukin 4 receptor gene [IL4R], interleukin 4 gene [IL4], interleukin 6 gene [IL6], prostaglandin-endoperoxide synthase 2 gene [PTGS2] (also known as COX2), transforming growth factor beta 1 gene [TGFB1], and tumor necrosis factor alpha gene [TNFA]) was evaluated.
Of the 23 polymorphisms, two were associated with risk for lung cancer. Compared with individuals with the wild-type (CC) variant, individuals carrying the minor allele variants of the IL-1β-511C>T promoter polymorphism (rs16944) (CT and TT) had decreased odds of lung cancer (OR = 0.74, [95% confidence interval (CI): 0.58-0.94] and OR = 0.71 [95% CI: 0.50-1.01], respectively, p = 0.03). Similar results were observed for the IL-1β-1464 C>G promoter polymorphism (rs1143623), with presence of the minor variants CG and CC having decreased odds of lung cancer (OR = 0.75 [95% CI: 0.59-0.95] and OR = 0.69 [95% CI: 0.46-1.03], respectively, p = 0.03). Survival was not influenced by genotype.
This study provides further evidence that IL1B promoter polymorphisms may modulate the risk for development of lung cancer.
慢性炎症与致癌作用有关，越来越多的证据表明其在肺癌中起作用。我们旨在评估炎症相关基因的遗传多态性在肺癌发展风险中的作用。
采用巢式病例对照研究设计，从β-胡萝卜素和视黄醇疗效试验（一项大型前瞻性肺癌化学预防试验）的参与者中选择了 625 例病例和 625 例匹配良好的对照。评估了肺癌发病率和生存率与 11 个炎症相关基因（干扰素γ基因[IFNG]、白细胞介素 10 基因[IL10]、白细胞介素 1 基因[IL1A]、白细胞介素 1β基因[IL1B]、白细胞介素 2 基因[IL2]、白细胞介素 4 受体基因[IL4R]、白细胞介素 4 基因[IL4]、白细胞介素 6 基因[IL6]、前列腺素内过氧化物合酶 2 基因[PTGS2]（也称为 COX2）、转化生长因子β 1 基因[TGFB1]和肿瘤坏死因子α基因[TNFA]）的 23 个多态性之间的关系。
在 23 个多态性中，有两个与肺癌风险相关。与野生型（CC）变异个体相比，白细胞介素 1β-511C>T 启动子多态性（rs16944）（CT 和 TT）携带较少等位基因变异的个体患肺癌的几率降低（OR=0.74，95%CI：0.58-0.94 和 OR=0.71，95%CI：0.50-1.01，p=0.03）。白细胞介素 1β-1464 C>G 启动子多态性（rs1143623）也观察到类似的结果，携带 CG 和 CC 较小变体的个体患肺癌的几率降低（OR=0.75，95%CI：0.59-0.95 和 OR=0.69，95%CI：0.46-1.03，p=0.03）。基因型对生存没有影响。
本研究进一步提供证据表明，白细胞介素 1B 启动子多态性可能调节肺癌发生的风险。
