结直肠癌遗传相关变异荟萃分析
创作:Lexi 审核:Lexi 2019年12月16日
  • 对158个不同基因的308个单核苷酸多态性(SNPs)进行荟萃分析;
  • 最初确定了16个位点的18个独立变异为“阳性”SNPs,其与CRC风险的关联高度可靠;
  • 49个位点的59个变异被归为“不太可信的阳性”SNPs;
  • 72.2%的“阳性”SNPs在三个大型全基因组关联研究(GWASs)中被成功复制,未被复制的被降级为“不太可信的阳性”(“阳性”变异减少到11个位点的14个变异);
  • 已报道的其余231个变异在该分析中未发现支持它们与CRC风险相关的证据。
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Lexi
为了解常见基因变异在结直肠癌(CRC)风险中的作用,最新发表在Gut杂志的一项研究报告了一份最新的领域简介,以及所有CRC遗传标记证据的综合评估。该荟萃分析纳入来自全基因组关联研究(GWASs)的苏格兰、加拿大和西班牙数据中的132个单核苷酸多态性(SNPs)。分析结果表明来自11个位点的14个变异可被归类为“阳性”SNPs,其与CRC风险的关联高度可靠。该荟萃分析提供了与CRC风险相关遗传变异的最新列表。
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Gut [IF:17.943]

Systematic meta-analyses, field synopsis and global assessment of the evidence of genetic association studies in colorectal cancer

结直肠癌遗传相关研究证据的系统性荟萃分析、领域简介和整体评价

10.1136/gutjnl-2019-319313

2019-12-09, Article

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Objective : To provide an understanding of the role of common genetic variations in colorectal cancer (CRC) risk, we report an updated field synopsis and comprehensive assessment of evidence to catalogue all genetic markers for CRC (CRCgene2).
Design : We included 869 publications after parallel literature review and extracted data for 1063 polymorphisms in 303 different genes. Meta-analyses were performed for 308 single nucleotide polymorphisms (SNPs) in 158 different genes with at least three independent studies available for analysis. Scottish, Canadian and Spanish data from genome-wide association studies (GWASs) were incorporated for the meta-analyses of 132 SNPs. To assess and classify the credibility of the associations, we applied the Venice criteria and Bayesian False-Discovery Probability (BFDP). Genetic associations classified as ‘positive’ and ‘less-credible positive’ were further validated in three large GWAS consortia conducted in populations of European origin.
Results: We initially identified 18 independent variants at 16 loci that were classified as ‘positive’ polymorphisms for their highly credible associations with CRC risk and 59 variants at 49 loci that were classified as ‘less-credible positive’ SNPs; 72.2% of the ‘positive’ SNPs were successfully replicated in three large GWASs and the ones that were not replicated were downgraded to ‘less-credible’ positive (reducing the ‘positive’ variants to 14 at 11 loci). For the remaining 231 variants, which were previously reported, our meta-analyses found no evidence to support their associations with CRC risk.
Conclusion : The CRCgene2 database provides an updated list of genetic variants related to CRC risk by using harmonised methods to assess their credibility.

First Authors:
Zahra Montazeri

Correspondence Authors:
Evropi Theodoratou

All Authors:
Zahra Montazeri,Xue Li,Christine Nyiraneza,Xiangyu Ma,Maria Timofeeva,Victoria Svinti,Xiangrui Meng,Yazhou He,Yacong Bo,Samuel Morgan,Sergi Castellví-Bel,Clara Ruiz-Ponte,Ceres Fernandez-Rozadilla,Ángel Carracedo,Antoni Castells,Timothy Bishop,Daniel Buchanan,Mark A Jenkins,Temitope O Keku,Annika Lindblom,Fränzel J B van Duijnhoven,Anna Wu,Susan M Farrington,Malcolm G Dunlop,Harry Campbell,Evropi Theodoratou,Wei Zheng,Julian Little

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