A Genome-Wide Association Scan (GWAS) for Mean Telomere Length Within the COGS Project: Identified Loci Show Little Association With Hormone-Related Cancer Risk

Hum Mol Genet. 2013 Dec 15;22(24):5056-64. doi: 10.1093/hmg/ddt355. Epub 2013 Jul 29.

Abstract

Mean telomere length (TL) in blood cells is heritable and has been reported to be associated with risks of several diseases, including cancer. We conducted a meta-analysis of three GWAS for TL (total n=2240) and selected 1629 variants for replication via the "iCOGS" custom genotyping array. All ∼200 000 iCOGS variants were analysed with TL, and those displaying associations in healthy controls (n = 15 065) were further tested in breast cancer cases (n = 11 024). We found a novel TL association (Ptrend < 4 × 10(-10)) at 3p14.4 close to PXK and evidence (Ptrend < 7 × 10(-7)) for TL loci at 6p22.1 (ZNF311) and 20q11.2 (BCL2L1). We additionally confirmed (Ptrend < 5 × 10(-14)) the previously reported loci at 3q26.2 (TERC), 5p15.3 (TERT) and 10q24.3 (OBFC1) and found supportive evidence (Ptrend < 5 × 10(-4)) for the published loci at 2p16.2 (ACYP2), 4q32.2 (NAF1) and 20q13.3 (RTEL1). SNPs tagging these loci explain TL differences of up to 731 bp (corresponding to 18% of total TL in healthy individuals), however, they display little direct evidence for association with breast, ovarian or prostate cancer risks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Chromosome Mapping
  • Female
  • Genetic Loci*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study*
  • Humans
  • Male
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Polymorphism, Single Nucleotide
  • Risk
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere Homeostasis / genetics*