Polymorphisms of the interleukin‐1 β gene are associated with increased risk of non‐small cell lung cancer

Abstract

Lung cancer is one of the leading causes of cancer death worldwide. Tobacco smoking is the main risk factor for lung cancer. Less than 20% of smokers develop lung cancer in their lifetime, however, indicating individual variations in lung cancer risk. Pro-inflammatory cytokines produced by inflammatory cells have been associated with inflammatory diseases and cancer. The IL1B gene, encoding IL-1␤ cytokine, contains several single nucleotide polymorphisms (SNPs). Two of these are in the promoter region, at positions ؊511 (C-T) and ؊31 (T-C). These polymorphisms have been associated with increased risk of developing a number of inflammatory diseases and gastric carcinoma. We genotyped the 2 polymorphisms in 251 non-small cell lung cancer patients from Norway and 272 healthy controls chosen from the general Norwegian population. The T allele at the ؊31 SNP (p ‫؍‬ 0.01) and C allele at ؊511 SNP (p < 0.01) were over represented in lung cancer cases. The homozygote subjects were particularly at higher risk of lung cancer with odds ratio of 2.39 (95% CI ‫؍‬ 1.29 -4.44) for ؊31T/T and 2.51 (95% CI ‫؍‬ 1.47-4.58) for ؊511C/C genotypes. In view of the significance of the p53 gene in lung carcinogenesis, we also analyzed the IL1B genotypes in relation to p53 mutations in the tumors. The results indicated that subjects having homozygote genotypes were more likely to have a mutation in the p53 gene (p ‫؍‬ 0.05). This is the first study to provide evidence for an association of 1L1B gene polymorphisms with lung cancer risk.

The Inflammatory Tumor Microenvironment, Epithelial Mesenchymal Transition and Lung Carcinogenesis

“…Polymorphisms in genes coding for inflammatory mediators found to be important in EMT, such as IL-1β, are associated with a heightened risk of gastric and lung cancer development [2,58]. Along with widespread inflammation, Snail is reported to be increased in pre-malignant lung lesions and in the lungs of patients with COPD [141].…”

“…Chronic overexpression of inflammatory mediators in the TME, as seen in smokers [1] and patients with non-small cell lung cancer (NSCLC) [2], can lead to increased tumor initiation, progression, invasion and metastasis [3]. The link between unresolved inflammation and cancer has been well established with estimates that 15% of cancer deaths are inflammation-related [4].…”

Genetic Polymorphism of Interleukin-1A (IL-1A), IL-1B, and IL-1 Receptor Antagonist (IL-1RN) and Prostate Cancer Risk

“…When IL-1RN, the anti-inflammatory cytokine, binds to the same receptors, no signal transduction will be elicited on and thereby the activity of IL-1 is blocked (McIntyre et al, 1991). IL-1 and IL-1RN polymorphisms have also been linked to several malignant tumors, including gastric cancer (El-Omar et al, 2000;Yamamoto-Furusho et al, 2011), hepatocellular cancer (Wang et al, 2003), lung cancer (Zienolddiny et al, 2004), and so on. But the association between polymorphisms of IL-1 family, including IL-1A, IL-1B, and IL-1RN and PCa risk was little studied.…”

Genetic Epidemiology of Cigarette Smoke–Induced Lung Disease

“…Inflammatory pathway genes have been targeted for study because of the chronic inflammation caused by cigarette smoke exposure. IL1, IL1B, IL1RN, TNFA, IL8, COX2, and IL10 SNPs have been associated with risk of lung cancer (43,(46)(47)(48)(49)(50)(51)(52)(53). In the Detroit lung cancer case-control study, associations between lung cancer risk and SNPs varied by race and by history of COPD (54).…”