A multi-omics study links TNS3 and SEPT7 to long-term former smoking NSCLC survival.
A multi-omics study links TNS3 and SEPT7 to long-term former smoking NSCLC survival.
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一项多摩尼克研究将TNS3和SEPT7与长期的以前吸烟NSCLC生存联系起来。
DOI：
10.1038/s41698-021-00182-3
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发表时间：
2021-05-17
影响因子：
7.9
通讯作者：
Christiani DC
中科院分区：
文献类型：
--
作者：
Shen S;Wei Y;Li Y;Duan W;Dong X;Lin L;You D;Tardon A;Chen C;Field JK;Hung RJ;Liu G;Zhu D;Amos CI;Su L;Zhao Y;Hu Z;Shen H;Zhang R;Chen F;Christiani DC
非小细胞肺癌（NSCLC）的遗传结构与吸烟状况有关。然而，长期戒烟对NSCLC患者预后的遗传贡献在很大程度上仍然未知。我们进行了一项全基因组关联研究，主要是对来自独立发现（n = 566）和验证（n = 733）集的1299例长期吸烟者的NSCLC患者的预后进行研究，并使用计算机功能预测和多组学分析来识别NSCLC患者的单核苷酸多态性（SNP）。我们进一步检测了在从不吸烟者、短期吸烟者、长期吸烟者和当前吸烟者中，对生存具有至少中等关联强度的SNP，并在SNP、基因、表达数量性状位点（eQTL）、增强子和途径水平上比较了它们的遗传相似性。我们确定了两个SNP，7p12.3处的rs34211819 TNS 3（P = 3.90 × 10−9）和7p14.2处的rs 1143149 SEPT 7（P = 9.75 × 10−9），与长期吸烟的NSCLC患者的生存率显著相关。两个SNP都与戒烟年数有显著的交互作用（rs34211819 TNS 3：Pinteraction = 8.0 × 10−4; rs 1143149 SEPT 7：Pinteraction = 0.003）。此外，计算机功能预测和多组学分析提供的证据表明，这些QTL与生存。此外，比较分析发现，与短期的前吸烟者或当前吸烟者相比，长期的前吸烟者和从不吸烟者之间的遗传相似性较高。途径富集分析表明，在长期吸烟者中存在一种与免疫途径相关的独特模式。这项研究提供了重要的见解，与长期吸烟的非小细胞肺癌相关的遗传结构。
The genetic architecture of non-small cell lung cancer (NSCLC) is relevant to smoking status. However, the genetic contribution of long-term smoking cessation to the prognosis of NSCLC patients remains largely unknown. We conducted a genome-wide association study primarily on the prognosis of 1299 NSCLC patients of long-term former smokers from independent discovery (n = 566) and validation (n = 733) sets, and used in-silico function prediction and multi-omics analysis to identify single nucleotide polymorphisms (SNPs) on prognostics with NSCLC. We further detected SNPs with at least moderate association strength on survival within each group of never, short-term former, long-term former, and current smokers, and compared their genetic similarity at the SNP, gene, expression quantitative trait loci (eQTL), enhancer, and pathway levels. We identified two SNPs, rs34211819TNS3 at 7p12.3 (P = 3.90 × 10−9) and rs1143149SEPT7 at 7p14.2 (P = 9.75 × 10−9), were significantly associated with survival of NSCLC patients who were long-term former smokers. Both SNPs had significant interaction effects with years of smoking cessation (rs34211819TNS3: Pinteraction = 8.0 × 10−4; rs1143149SEPT7: Pinteraction = 0.003). In addition, in silico function prediction and multi-omics analysis provided evidence that these QTLs were associated with survival. Moreover, comparison analysis found higher genetic similarity between long-term former smokers and never-smokers, compared to short-term former smokers or current smokers. Pathway enrichment analysis indicated a unique pattern among long-term former smokers that was related to immune pathways. This study provides important insights into the genetic architecture associated with long-term former smoking NSCLC.
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影响因子：
30.8
作者：
Das, Sayantan;Forer, Lukas;Schoenherr, Sebastian;Sidore, Carlo;Locke, Adam E.;Kwong, Alan;Vrieze, Scott I.;Chew, Emily Y.;Levy, Shawn;McGue, Matt;Schlessinger, David;Stambolian, Dwight;Loh, Po-Ru;Iacono, William G.;Swaroop, Anand;Scott, Laura J.;Cucca, Francesco;Kronenberg, Florian;Boehnke, Michael;Abecasis, Goncalo R.;Fuchsberger, Christian
通讯作者：
Fuchsberger, Christian
DOI：
10.1093/jnci/djs136
发表时间：
2012-04-04
期刊：
Journal of the National Cancer Institute
影响因子：
--
作者：
Moolgavkar SH;Holford TR;Levy DT;Kong CY;Foy M;Clarke L;Jeon J;Hazelton WD;Meza R;Schultz F;McCarthy W;Boer R;Gorlova O;Gazelle GS;Kimmel M;McMahon PM;de Koning HJ;Feuer EJ
通讯作者：
Feuer EJ
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
7
作者：
Boyle AP;Hong EL;Hariharan M;Cheng Y;Schaub MA;Kasowski M;Karczewski KJ;Park J;Hitz BC;Weng S;Cherry JM;Snyder M
通讯作者：
Snyder M
影响因子：
30.8
作者：
Loh, Po-Ru;Danecek, Petr;Palamara, Pier Francesco;Fuchsberger, Christian;Reshef, Yakir A.;Finucane, Hilary K.;Schoenherr, Sebastian;Forer, Lukas;McCarthy, Shane;Abecasis, Goncalo R.;Durbin, Richard;Price, Alkes L.
通讯作者：
Price, Alkes L.