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Telomere structure and maintenance gene variants and risk of five cancer types.

Publication ,  Journal Article
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 ...
Published in: Int J Cancer
December 15, 2016

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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Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

December 15, 2016

Volume

139

Issue

12

Start / End Page

2655 / 2670

Location

United States

Related Subject Headings

  • White People
  • Telomere Homeostasis
  • Telomere
  • Telomerase
  • Risk
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Neoplasms
  • Linkage Disequilibrium
 

Citation

APA
Chicago
ICMJE
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Karami, S., Han, Y., Pande, M., Cheng, I., Rudd, J., Pierce, B. L., … GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL, . (2016). Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer, 139(12), 2655–2670. https://doi.org/10.1002/ijc.30288
Karami, Sara, Younghun Han, Mala Pande, Iona Cheng, James Rudd, Brandon L. Pierce, Ellen L. Nutter, et al. “Telomere structure and maintenance gene variants and risk of five cancer types.Int J Cancer 139, no. 12 (December 15, 2016): 2655–70. https://doi.org/10.1002/ijc.30288.
Karami S, Han Y, Pande M, Cheng I, Rudd J, Pierce BL, et al. Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer. 2016 Dec 15;139(12):2655–70.
Karami, Sara, et al. “Telomere structure and maintenance gene variants and risk of five cancer types.Int J Cancer, vol. 139, no. 12, Dec. 2016, pp. 2655–70. Pubmed, doi:10.1002/ijc.30288.
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. Telomere structure and maintenance gene variants and risk of five cancer types. Int J Cancer. 2016 Dec 15;139(12):2655–2670.
Journal cover image

Published In

Int J Cancer

DOI

EISSN

1097-0215

Publication Date

December 15, 2016

Volume

139

Issue

12

Start / End Page

2655 / 2670

Location

United States

Related Subject Headings

  • White People
  • Telomere Homeostasis
  • Telomere
  • Telomerase
  • Risk
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Odds Ratio
  • Neoplasms
  • Linkage Disequilibrium