A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk.
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.
Pooley, KA; Bojesen, SE; Weischer, M; Nielsen, SF; Thompson, D; Amin Al Olama, A; Michailidou, K; Tyrer, JP; Benlloch, S; Brown, J; Audley, T; Luben, R; Khaw, K-T; Neal, DE; Hamdy, FC; Donovan, JL; Kote-Jarai, Z; Baynes, C; Shah, M; Bolla, MK; Wang, Q; Dennis, J; Dicks, E; Yang, R; Rudolph, A; Schildkraut, J; Chang-Claude, J; Burwinkel, B; Chenevix-Trench, G; Pharoah, PDP; Berchuck, A; Eeles, RA; Easton, DF; Dunning, AM; Nordestgaard, BG
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