國家衛生研究院 NHRI:Item 3990099045/8211
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    题名: Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
    作者: Wang, Z;Zhu, B;Zhang, M;Parikh, H;Jia, J;Chung, CC;Sampson, JN;Hoskins, JW;Hutchinson, A;Burdette, L;Ibrahim, A;Hautman, C;Raj, PS;Abnet, CC;Adjei, AA;Ahlbom, A;Albanes, D;Allen, NE;Ambrosone, CB;Aldrich, M;Amiano, P;Amos, C;Andersson, U;Andriole, G, Jr.;Andrulis, IL;Arici, C;Arslan, AA;Austin, MA;Baris, D;Barkauskas, DA;Bassig, BA;Beane Freeman, LE;Berg, CD;Berndt, SI;Bertazzi, PA;Biritwum, RB;Black, A;Blot, W;Boeing, H;Boffetta, P;Bolton, K;Boutron-Ruault, MC;Bracci, PM;Brennan, P;Brinton, LA;Brotzman, M;Bueno-de-Mesquita, HB;Buring, JE;Butler, MA;Cai, Q;Cancel-Tassin, G;Canzian, F;Cao, G;Caporaso, NE;Carrato, A;Carreon, T;Carta, A;Chang, GC;Chang, IS;Chang-Claude, J;Che, X;Chen, CJ;Chen, CY;Chen, CH;Chen, C;Chen, KY;Chen, YM;Chokkalingam, AP;Chu, LW;Clavel-Chapelon, F;Colditz, GA;Colt, JS;Conti, D;Cook, MB;Cortessis, VK;Crawford, ED;Cussenot, O;Davis, FG;De Vivo, I;Deng, X;Ding, T;Dinney, CP;Di Stefano, AL;Diver, WR;Duell, EJ;Elena, JW;Fan, JH;Feigelson, HS;Feychting, M;Figueroa, JD;Flanagan, AM;Fraumeni, JF, Jr.;Freedman, ND;Fridley, BL;Fuchs, CS;Gago-Dominguez, M;Gallinger, S;Gao, YT;Gapstur, SM;Garcia-Closas, M, .;et al.
    贡献者: National Institute of Cancer Research;Division of Biostatistics and Bioinformatics
    摘要: Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
    日期: 2014-12
    關聯: Human Molecular Genetics. 2014 Dec;23(24):6616-6633.
    Link to: http://dx.doi.org/10.1093/hmg/ddu363
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0964-6906&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000347921900017
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84938138638
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