Common variants of pro-inflammatory gene IL1B and interactions with PPP1R13L and POLR1G in relation to lung cancer among Northeast Chinese

• Published in: Scientific reports 2023-05, Vol.13 (1), p.7352-7352, Article 7352
• Main Authors: Yin, Jiaoyang, Wang, Chunhong, Vogel, Ulla, Ma, Yegang, Zhang, Ying, Wang, Huiwen, Sun, Zhenxiang, Du, Shuai
• Format: Article
• Language: English
• Subjects: 631/67; 692/4017; 692/53; Case-Control Studies; East Asian People; Environmental factors; Genetic analysis; Genetic Predisposition to Disease; Haplotypes; Health risks; Humanities and Social Sciences; Humans; IL-1β; Inflammation; Interleukin 1; Interleukin-1beta - genetics; Intracellular Signaling Peptides and Proteins - genetics; Lung cancer; Lung carcinoma; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; multidisciplinary; Polymorphism, Single Nucleotide; Repressor Proteins - genetics; Science; Science (multidisciplinary); Single-nucleotide polymorphism; Smoking; Squamous cell carcinoma
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-023-34069-z

Lung cancer is a complex disease influenced by a variety of genetic and environmental factors. The cytokine interleukin 1 encoded by IL1B is an important mediator of the inflammatory response, and is involved in a variety of cellular activities. The effect of single nucleotide polymorphisms (SNP) at IL1B has been investigated in relation to cancer with inconsistent results. This Northeastern-Chinese case–control study involving 627 cases and 633 controls evaluated the role of three haplotype-tagging single nucleotide polymorphisms (htSNP) (rs1143633, rs3136558 and rs1143630) representing 95% of the common haplotype diversity across the IL1B gene and assessed interactions with IL1B , PPP1R13L , POLR1G and smoking duration in relation to lung cancer risk. The analyses of five genetic models showed associations with lung cancer risk for rs1143633 in the dominant model [adjusted-OR (95% CI) = 0.67 (0.52–0.85), P  = 0.0012] and rs3136558 in the recessive model [adjusted-OR (95% CI) = 1.44 (1.05–1.98), P  = 0.025]. Haplotype4 was associated with increased lung cancer risk [adjusted-OR (95% CI) = 1.55 (1.07–2.24), P  = 0.021]. The variant G-allele of rs1143633 was protective in smoking sub-group of > 20 years. Using multifactor dimensionality reduction (MDR) analyses, we identified the three best candidate models of interactions and smoking-duration or IL1B rs1143633 as main effect. In conclusion, our findings suggest that IL1B SNP rs1143633 may associate with lower risk of lung cancer, confirming previously identified marker; IL1B SNP rs3136558 and haplotype4 consisting of IL1B htSNPs may associate with increasing risk of lung cancer; interactions of IL1B with POLR1G or PPP1R13L or smoking-duration, which is independent or combined, may involve in risk of lung cancer and lung squamous cell carcinoma.