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Telomere structure and maintenance gene variants and risk of five cancer types
Author(s) -
Karami Sara,
Han Younghun,
Pande Mala,
Cheng Iona,
Rudd James,
Pierce Brandon L.,
Nutter Ellen L.,
Schumacher Fredrick R.,
KoteJarai Zsofia,
Lindstrom Sara,
Witte John S.,
Fang Shenying,
Han Jiali,
Kraft Peter,
Hunter David J.,
Song Fengju,
Hung Rayjean J.,
McKay James,
Gruber Stephen B.,
Chanock Stephen J.,
Risch Angela,
Shen Hongbing,
Haiman Christopher A.,
Boardman Lisa,
Ulrich Cornelia M.,
Casey Graham,
Peters Ulrike,
Amin Al Olama Ali,
Berchuck Andrew,
Berndt Sonja I.,
Bezieau Stephane,
Brennan Paul,
Brenner Hermann,
Brinton Louise,
Caporaso Neil,
Chan Andrew T.,
ChangClaude Jenny,
Christiani David C.,
Cunningham Julie M.,
Easton Douglas,
Eeles Rosalind A.,
Eisen Timothy,
Gala Manish,
Gallinger Steven J.,
Gayther Simon A.,
Goode Ellen L.,
Grönberg Henrik,
Henderson Brian E.,
Houlston Richard,
Joshi Amit D.,
Küry Sébastien,
Landi Mari T.,
Le Marchand Loic,
Muir Kenneth,
Newcomb Polly A.,
PermuthWey Jenny,
Pharoah Paul,
Phelan Catherine,
Potter John D.,
Ramus Susan J.,
Risch Harvey,
Schildkraut Joellen,
Slattery Martha L.,
Song Honglin,
Wentzensen Nicolas,
White Emily,
Wiklund Fredrik,
Zanke Brent W.,
Sellers Thomas A.,
Zheng Wei,
Chatterjee Nilanjan,
Amos Christopher I.,
Doherty Jennifer A.
Publication year - 2016
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30288
Subject(s) - telomere , biology , single nucleotide polymorphism , prostate cancer , prostate , colorectal cancer , breast cancer , oncology , telomerase reverse transcriptase , cancer , lung cancer , medicine , cancer research , telomerase , gene , genetics , genotype
Telomeres cap chromosome ends, protecting them from degradation, double‐strand breaks, and end‐to‐end fusions. Telomeres are maintained by telomerase, a reverse transcriptase encoded by TERT , and an RNA template encoded by TERC . Loci in the TERT and adjoining CLPTM1L region are associated with risk of multiple cancers. We therefore investigated associations between variants in 22 telomere structure and maintenance gene regions and colorectal, breast, prostate, ovarian, and lung cancer risk. We performed subset‐based meta‐analyses of 204,993 directly‐measured and imputed SNPs among 61,851 cancer cases and 74,457 controls of European descent. Independent associations for SNP minor alleles were identified using sequential conditional analysis (with gene‐level p value cutoffs ≤3.08 × 10 −5 ). Of the thirteen independent SNPs observed to be associated with cancer risk, novel findings were observed for seven loci. Across the DCLRE1B region, rs974494 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Across the TERC region, rs75316749 was positively associated with colorectal, breast, ovarian, and lung cancers. Across the DCLRE1B region, rs974404 and rs12144215 were inversely associated with prostate and lung cancers, and colorectal, breast, and prostate cancers, respectively. Near POT1 , rs116895242 was inversely associated with colorectal, ovarian, and lung cancers, and RTEL1 rs34978822 was inversely associated with prostate and lung cancers. The complex association patterns in telomere‐related genes across cancer types may provide insight into mechanisms through which telomere dysfunction in different tissues influences cancer risk.