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

on behalf of GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2655-2670
Number of pages16
JournalInternational Journal of Cancer
Volume139
Issue number12
DOIs
StatePublished - Dec 15 2016

Fingerprint

Telomere
Prostatic Neoplasms
Maintenance
Lung Neoplasms
Colorectal Neoplasms
Breast Neoplasms
Genes
Neoplasms
Ovarian Neoplasms
Single Nucleotide Polymorphism
Neoplasm Genes
Telomerase
Meta-Analysis
Chromosomes
Alleles
RNA

Keywords

  • breast cancer
  • cancer risk
  • colorectal cancer
  • GWAS
  • lung cancer
  • meta-analysis
  • ovarian cancer
  • prostate cancer
  • telomere maintenance
  • telomere structure

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

on behalf of 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. International Journal of Cancer, 139(12), 2655-2670. https://doi.org/10.1002/ijc.30288

Telomere structure and maintenance gene variants and risk of five cancer types. / on behalf of GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL.

In: International Journal of Cancer, Vol. 139, No. 12, 15.12.2016, p. 2655-2670.

Research output: Contribution to journalArticle

on behalf of 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', International Journal of Cancer, vol. 139, no. 12, pp. 2655-2670. https://doi.org/10.1002/ijc.30288
on behalf of GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL. Telomere structure and maintenance gene variants and risk of five cancer types. International Journal of Cancer. 2016 Dec 15;139(12):2655-2670. https://doi.org/10.1002/ijc.30288
on behalf of GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL. / Telomere structure and maintenance gene variants and risk of five cancer types. In: International Journal of Cancer. 2016 ; Vol. 139, No. 12. pp. 2655-2670.
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AU - Karami, Sara

AU - Han, Younghun

AU - Pande, Mala

AU - Cheng, Iona

AU - Rudd, James

AU - Pierce, Brandon L.

AU - Nutter, Ellen L.

AU - Schumacher, Fredrick R.

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AU - Chanock, Stephen J.

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AU - Shen, Hongbing

AU - Haiman, Christopher A.

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AU - Casey, Graham

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AU - Berchuck, Andrew

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AU - Caporaso, Neil

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KW - cancer risk

KW - colorectal cancer

KW - GWAS

KW - lung cancer

KW - meta-analysis

KW - ovarian cancer

KW - prostate cancer

KW - telomere maintenance

KW - telomere structure

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