Telomere structure and maintenance gene variants and risk of five cancer types.
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Date
2016-12-15Author
Karami, S
Han, Y
Pande, M
Cheng, I
Rudd, J
Pierce, BL
Nutter, EL
Schumacher, FR
Kote-Jarai, Z
Lindstrom, S
Witte, JS
Fang, S
Han, J
Kraft, P
Hunter, DJ
Song, F
Hung, RJ
McKay, J
Gruber, SB
Chanock, SJ
Risch, A
Shen, H
Haiman, CA
Boardman, L
Ulrich, CM
Casey, G
Peters, U
Amin Al Olama, A
Berchuck, A
Berndt, SI
Bezieau, S
Brennan, P
Brenner, H
Brinton, L
Caporaso, N
Chan, AT
Chang-Claude, J
Christiani, DC
Cunningham, JM
Easton, D
Eeles, RA
Eisen, T
Gala, M
Gallinger, SJ
Gayther, SA
Goode, EL
Grönberg, H
Henderson, BE
Houlston, R
Joshi, AD
Küry, S
Landi, MT
Le Marchand, L
Muir, K
Newcomb, PA
Permuth-Wey, J
Pharoah, P
Phelan, C
Potter, JD
Ramus, SJ
Risch, H
Schildkraut, J
Slattery, ML
Song, H
Wentzensen, N
White, E
Wiklund, F
Zanke, BW
Sellers, TA
Zheng, W
Chatterjee, N
Amos, CI
Doherty, JA
GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL,
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Subject
GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL
Telomere
Humans
Neoplasms
Genetic Predisposition to Disease
Telomerase
Odds Ratio
Risk
Case-Control Studies
Linkage Disequilibrium
Polymorphism, Single Nucleotide
Alleles
European Continental Ancestry Group
Genetic Variation
Genome-Wide Association Study
Genetic Association Studies
Telomere Homeostasis
Research team
Cancer Genomics
Oncogenetics
Language
eng
Date accepted
2016-06-21
License start date
2016-12
Citation
International journal of cancer, 2016, 139 (12), pp. 2655 - 2670
Publisher
WILEY