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PLOS Genetics文章:揭示肺鳞癌易感基因

日期:2019/04/11  来源:新葡萄京娱乐场官方网站

  

  肺癌是世界范围内最常见和致死最多的癌症。肺癌主要分为肺鳞癌和肺腺癌两种组织类型,而吸烟与肺鳞癌的发生更为密切。之前全基因组关联分析 (GWAS) 研究发现了若干与肺癌易感性相关的SNP位点和基因,本研究则专注于汉族人肺鳞癌类型进行GWAS分析。研究人员首先对833名肺鳞癌患者,和3,094名正常对照个体进行了全基因组关联分析。在随后的验证阶段进一步对另一组2,223名肺鳞癌患者,以及6,409名对照个体进行了检测。最终鉴定出了1个与肺鳞癌相关联的新的风险位点rs12296850,该SNP位于染色体12q23.1区域的SLC17A8-NR1H4基因。这个汉族人肺鳞癌风险位点与肺腺癌的发生并无显著关联(基于4,368肺腺癌患者和 9,486名正常对照者的关联分析)。
  本研究相关成果发表在2013年1月的Plos Genetics杂志上。南京医科大学公共卫生学院沈洪兵教授、胡志斌教授和中国医学科学院肿瘤医院林东昕教授为这篇论文的共同通讯编辑。
  在这项研究中,其中13q12.12 和22q12.2为在汉族人群中发现的新的风险位点。这一研究发现将帮助科学家们更深了解汉族人群肺鳞癌发生的分子机制,以及风险预测和预防等具有重要价值。本研究中Affymetrix SNP6.0芯片检测和Sequenom SNP验证工作均在北京新葡萄京娱乐场官方网站生物技术有限企业完成。


原文摘要

        Genome-wide association study identifies a novel susceptibility locus at 12q23.1 for lung squamous cell carcinoma in han chinese.

  Adenocarcinoma (AC) and squamous cell carcinoma (SqCC) are two major histological subtypes of lung cancer. Genome-wide association studies (GWAS) have made considerable advances in the understanding of lung cancer susceptibility. Obvious heterogeneity has been observed between different histological subtypes of lung cancer, but genetic determinants in specific to lung SqCC have not been systematically investigated. Here, we performed the GWAS analysis specifically for lung SqCC in 833 SqCC cases and 3,094 controls followed by a two-stage replication in additional 2,223 lung SqCC cases and 6,409 controls from Chinese populations. We found that rs12296850 in SLC17A8-NR1H4 gene region at12q23.1 was significantly associated with risk of lung SqCC at genome-wide significance level [additive model: odds ratio (OR)?=?0.78, 95% confidence interval (CI)?=?0.72-0.84, P?=?1.19×10(-10)]. Subjects carrying AG or GG genotype had a 26% (OR?=?0.74, 95% CI?=?0.67-0.81) or 32% (OR?=?0.68, 95% CI?=?0.56-0.83) decreased risk of lung SqCC, respectively, as compared with AA genotype. However, we did not observe significant association between rs12296850 and risk of lung AC in a total of 4,368 cases with lung AC and 9,486 controls (OR?=?0.96, 95% CI?=?0.90-1.02, P?=?0.173). These results indicate that genetic variations on chromosome 12q23.1 may specifically contribute to lung SqCC susceptibility in Chinese population.
原文出处http://www.plosgenetics.org/article/info%3Adoi%2F10.1371%2Fjournal.pgen.1003190

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