Authors:
KA Pooley, SE Bojesen, M Weischer, SF Nielsen, D Thompson, A Amin Al Olama, K Michailidou, JP Tyrer, S Benlloch, J Brown, T Audley, R Luben, K-T Khaw, DE Neal, FC Hamdy, JL Donovan, Z Kote-Jarai, C Baynes, M Shah, MK Bolla, Q Wang, J Dennis, E Dicks, R Yang, A Rudolph, J Schildkraut, J Chang-Claude, B Burwinkel, G Chenevix-Trench, PDP Pharoah, A Berchuck, RA Eeles, DF Easton, AM Dunning, BG Nordestgaard
Journal name: 
Hum Mol Genet
Citation info: 
22(24):5056-5064
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.
DOI: 
http://doi.org/10.1093/hmg/ddt355
Research group: 
Neal Group
E-pub date: 
15 Dec 2013