IL1B gene polymorphisms, age and the risk of non-small cell lung cancer in a Chinese population
IL1B gene polymorphisms, age and the risk of non-small cell lung cancer in a Chinese population
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中国人群IL1B基因多态性、年龄与非小细胞肺癌风险
DOI：
10.1016/j.lungcan.2015.06.009
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发表时间：
2015-09-01
期刊：
影响因子：
5.3
通讯作者：
Wang, Jiucun
中科院分区：
文献类型：
--
作者：
Li, Yanan;Zhao, Wei;Wang, Jiucun
背景/目标：IL1B rs12621220 G/A（-3893），rs1143623 G/C（-1464），rs 16944 T/C（-511）和rs 1143627 C/T（-31）与非小细胞肺癌（NSCLC）相关，并形成一种特异性单倍型（GGCT）这与欧洲人群中11.113基因表达增加和NSCLC风险增加有关。目前在中国人群中仅对rs 16944 T/C（-511）和rs 1143627 C/T（-31）两个SNP位点进行了研究，但结果不一致。方法：采用SNPscan（TM）Genotyping系统对889例肺癌患者和1005例对照者进行IL 1B单核苷酸多态性（SNPs）基因分型。我们使用逻辑回归，以确定每个SNP和NSCLC之间的关联估计OR和95%置信区间（CI），控制潜在的混杂因素，如appropriate.Results：在63岁以上的受试者，检测到NSCLC和IL 1B SNP之间的显着关联。对于rs 12621220 G>A（-3893）和rs 1143623 G>C（-1464），与祖先基因型相比，杂合变异与NSCLC风险降低显著相关，校正比值比（aOR）=0.710（0.516，0.976），P=0.035; aOR=0.643（0.466，0.886），P=0.007。rs 16944 T>C（-511）和rs 1143627 C>T（-31）纯合子变异与NSCLC发病风险显著相关，aOR分别为1.482（1.084，2.025），P=0.014和1.450（1.055，1.994），P=0.022。单倍型结构推断表明rs 12621220 G/A（-3893）、rs 1143623 G/C（-1464）、rs 16944 T/C（-511）和rs 1143627 C/T（-31）构成2种危险单倍型（GGCC和ACTT）在所有受试者中均存在连锁不平衡，经10万次排列测验后，病例组与对照组之间的频率有显著性差异结论：11.113个SNPs可能与中国人群NSCLC的发病有关。(C)2015爱思唯尔爱尔兰有限公司版权所有。
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 11.113 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 (TM) 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 11.113 SNPs might be implicated in the pathogenesis of NSCLC in the Chinese population. (C) 2015 Elsevier Ireland Ltd. All rights reserved.