Yanan Li1, Wei Zhao1, ZhenHong Zhao1, Junjie Wu2, Linqi Chen1, Yanyun Ma1, Qiang Li3, Daru Lu1, Li Jin1, Jiucun Wang4. 1. National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, China. 2. National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, China; Departments of Pneumology, Changhai Hospital of Shanghai, Shanghai, China. 3. Departments of Pneumology, Changhai Hospital of Shanghai, Shanghai, China. 4. National Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, China. Electronic address: jcwang@fudan.edu.cn.
Abstract
BACKGROUND/ OBJECTIVES: IL1B rs12621220G/A (-3893), rs1143623G/C (-1464), rs16944T/C (-511) and rs1143627C/T (-31) were previously reported to be associated with non-small cell lung cancer (NSCLC) and formed a specific haplotype (GGCT) which was associated with increased IL1B gene expression and increased risk of NSCLC in European populations. Only the two SNPs of rs16944T/C (-511) and rs1143627C/T (-31) have been studied in Chinese populations, and the results were conflicting. Thus we studied the association of the above four SNPs with NSCLC in a large Chinese population. METHODS: We genotyped IL1B SNPs in a case-control study with 889 lung cancer cases and 1005 controls using the SNPscan Genotyping system. We used logistic regression to determine the association between each SNP and NSCLC estimated by ORs and their 95% confidence intervals (CIs), controlling for Potential confounders as appropriate. RESULTS: In subjects over age 63, significant associations were detected between NSCLC and IL1B SNPs. For rs12621220G>A (-3893) and rs1143623G>C (-1464), heterozygous variants, when compared with ancestral genotype, were significantly associated with decreased risk of NSCLC, with adjusted odds ratio (aOR)=0.710 (0.516, 0.976), P=0.035 and aOR=0.643 (0.466, 0.886), P=0.007, respectively. For rs16944T>C (-511) and rs1143627C>T (-31), homozygous variants were significantly associated with increased risk of NSCLC, with aOR=1.482 (1.084, 2.025), P=0.014 and aOR=1.450 (1.055, 1.994), P=0.022, respectively. Inference of the haplotype structures showed that rs12621220G/A (-3893), rs1143623G/C (-1464), rs16944T/C (-511) and rs1143627C/T (-31) formed two risk haplotypes (GGCC and ACTT) with linkage disequilibrium in all subjects, and they have significantly different frequencies between cases and controls after the permutation tests for one hundred thousand times (P=0.0000E0). CONCLUSIONS: Our study provided evidence that IL1B SNPs might be implicated in the pathogenesis of NSCLC in the Chinese population.
BACKGROUND/ OBJECTIVES:IL1B rs12621220G/A (-3893), rs1143623G/C (-1464), rs16944T/C (-511) and rs1143627C/T (-31) were previously reported to be associated with non-small cell lung cancer (NSCLC) and formed a specific haplotype (GGCT) which was associated with increased IL1B gene expression and increased risk of NSCLC in European populations. Only the two SNPs of rs16944T/C (-511) and rs1143627C/T (-31) have been studied in Chinese populations, and the results were conflicting. Thus we studied the association of the above four SNPs with NSCLC in a large Chinese population. METHODS: We genotyped IL1B SNPs in a case-control study with 889 lung cancer cases and 1005 controls using the SNPscan Genotyping system. We used logistic regression to determine the association between each SNP and NSCLC estimated by ORs and their 95% confidence intervals (CIs), controlling for Potential confounders as appropriate. RESULTS: In subjects over age 63, significant associations were detected between NSCLC and IL1B SNPs. For rs12621220G>A (-3893) and rs1143623G>C (-1464), heterozygous variants, when compared with ancestral genotype, were significantly associated with decreased risk of NSCLC, with adjusted odds ratio (aOR)=0.710 (0.516, 0.976), P=0.035 and aOR=0.643 (0.466, 0.886), P=0.007, respectively. For rs16944T>C (-511) and rs1143627C>T (-31), homozygous variants were significantly associated with increased risk of NSCLC, with aOR=1.482 (1.084, 2.025), P=0.014 and aOR=1.450 (1.055, 1.994), P=0.022, respectively. Inference of the haplotype structures showed that rs12621220G/A (-3893), rs1143623G/C (-1464), rs16944T/C (-511) and rs1143627C/T (-31) formed two risk haplotypes (GGCC and ACTT) with linkage disequilibrium in all subjects, and they have significantly different frequencies between cases and controls after the permutation tests for one hundred thousand times (P=0.0000E0). CONCLUSIONS: Our study provided evidence that IL1B SNPs might be implicated in the pathogenesis of NSCLC in the Chinese population.
Authors: Keith D Eaton; Perrin E Romine; Gary E Goodman; Mark D Thornquist; Matt J Barnett; Effie W Petersdorf Journal: J Thorac Oncol Date: 2018-03-23 Impact factor: 15.609