文章摘要
朱小琪,司妮平,付晓宇,程静雯,秦娜,刘逸辰,田甜,马红霞,褚敏捷.一种新的调控型遗传变异与中国人群肺癌发病风险的关系:两阶段病例-对照研究[J].中华流行病学杂志,2021,42(11):2053-2059
一种新的调控型遗传变异与中国人群肺癌发病风险的关系:两阶段病例-对照研究
Association between a novel regulatory genetic variants and lung cancer risk in Chinese: a two-stage case-control study
收稿日期:2021-03-31  出版日期:2021-11-20
DOI:10.3760/cma.j.cn112338-20210331-00262
中文关键词: 肺癌;调控型数量性状位点;单核苷酸多态性
英文关键词: Lung cancer;Regulatory quantitative trait loci;Single nucleotide polymorphism
基金项目:国家自然科学基金(81703297)
作者单位E-mail
朱小琪 南通大学公共卫生学院流行病与卫生统计学系 226019  
司妮平 南通大学公共卫生学院流行病与卫生统计学系 226019  
付晓宇 南通大学公共卫生学院流行病与卫生统计学系 226019  
程静雯 南通大学公共卫生学院流行病与卫生统计学系 226019  
秦娜 南京医科大学公共卫生学院流行病学系 211166  
刘逸辰 南通大学公共卫生学院流行病与卫生统计学系 226019  
田甜 南通大学公共卫生学院流行病与卫生统计学系 226019  
马红霞 南京医科大学公共卫生学院流行病学系 211166  
褚敏捷 南通大学公共卫生学院流行病与卫生统计学系 226019 chuminjie@ntu.edu.cn 
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中文摘要:
      目的 调控型数量性状位点(regQTL)理论可以帮助研究者从三维角度评估单核苷酸多态性(SNPs)对重要生物信号的调控作用。本研究拟探讨regQTL-SNPs对肺癌易感性的影响。方法 基于regQTL理论,利用已知的肺癌regQTL-SNPs数据库,筛选出全基因组关联研究(GWAS)报道的肺癌易感区域中发挥regQTL功能的SNPs。并通过两阶段病例-对照研究(初筛阶段:2 331例肺癌病例和3 077例健康对照;验证阶段:626例肺癌病例和667例健康对照),进一步明确上述regQTL-SNPs与肺癌易感性的关联。结果 在肺癌GWAS已报道的易感区域中,共筛选出8个regQTL-SNPs。人群易感性分析的初筛阶段,研究结果显示3个regQTL-SNPs与肺癌的发病风险存在统计学关联(P<0.05),验证阶段结果显示,位于ADRA1A基因上的rs6998591突变等位基因T可以显著增加肺癌的发病风险(相加模型:OR=1.33,95%CI:1.01~1.74,P=0.040),而位于ACTA2基因上的rs11202916突变等位基因G可以明显降低肺癌的发病风险(隐性模型:OR=0.71,95%CI:0.52~0.96,P=0.026)。分层分析结果显示,rs6998591的突变等位基因T显著增加肺鳞癌的发病风险(相加模型:OR=1.53,95%CI:1.01~2.32,P=0.043),而rs11202916的突变等位基因G显著降低肺腺癌的发病风险(相加模型:OR=0.83,95%CI:0.69~0.98,P=0.031)。基因环境交互作用分析显示携带rs6998591突变等位基因T且吸烟的个体与不携带rs6998591突变等位基因T且不吸烟的个体相比,肺癌的发病风险增加235%(OR=3.35,95%CI:2.10~5.34,P<0.001)。结论 肺癌GWAS已报道的易感区域中存在2个发挥regQTL功能的SNPs,并且可以显著影响肺癌的易感性。
英文摘要:
      Objective Regulatory quantitative trait loci (regQTL) theory can help to evaluate the regulation function of single nucleotide polymorphisms (SNPs) on crucial biological signals from a three-dimensional perspective. The aim of this study was to investigate the effect of these regQTL-SNPs on the susceptibility of lung cancer. Methods Based on the regQTL theory, using the database of identified lung cancer regQTL-SNPs, we screened the SNPs that may function as regQTL in the reported susceptible regions of lung cancer by genome-wide association study(GWAS), and a two-stage case-control study was conducted (screening stage:2 331 lung cancer cases and 3 077 healthy controls; validation stage:626 lung cancer cases and 667 healthy controls) to definite the association of related regQTL-SNPs with the susceptibility of lung cancer. Results A total of 8 regQTL-SNPs were screened in the reported susceptible regions of lung cancer by GWAS. Among which, 3 SNPs were significantly associated with the risk of lung cancer (P<0.05) in the screening stage. Further validation results indicated that the variant T allele of rs6998591 in ADRA1A was significantly associated with increased risk of lung cancer (additive model:OR=1.33, 95%CI:1.01-1.74, P=0.040). In addition, the variant G allele of rs11202916 in ACTA2 was significantly associated with decreased risk of lung cancer (recessive model:OR=0.71, 95%CI:0.52-0.96, P=0.026). Stratified analysis indicated that the variant T allele of rs6998591 significantly increased lung squamous cell carcinoma risk (additive model:OR=1.53, 95%CI:1.01-2.32, P=0.043), while the variant G allele of rs11202916 significantly decreased lung adenocarcinoma risk (additive model:OR=0.83, 95%CI:0.69-0.98, P=0.031). Gene-environment interaction analysis indicated that the risk of developing lung cancer increased by 235% in smoking individuals carrying rs6998591 variant T allele compared with those non-smoking individuals carrying no rs6998591 variant T allele(OR=3.35,95%CI:2.10-5.34,P<0.001). Conclusion There are two regQTL-SNPs that could significantly affect the susceptibility of lung cancer in the GWAS reported susceptible regions of lung cancer.
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