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A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk.


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.

SUBMITTER: Pooley KA 

PROVIDER: S-EPMC3836481 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature

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A genome-wide association scan (GWAS) for mean telomere length within the COGS project: identified loci show little association with hormone-related cancer risk.

Pooley Karen A KA   Bojesen Stig E SE   Weischer Maren M   Nielsen Sune F SF   Thompson Deborah D   Amin Al Olama Ali A   Michailidou Kyriaki K   Tyrer Jonathan P JP   Benlloch Sara S   Brown Judith J   Audley Tina T   Luben Robert R   Khaw K-T KT   Neal David E DE   Hamdy Freddie C FC   Donovan Jenny L JL   Kote-Jarai Zsofia Z   Baynes Caroline C   Shah Mitul M   Bolla Manjeet K MK   Wang Qin Q   Dennis Joe J   Dicks Ed E   Yang Rongxi R   Rudolph Anja A   Schildkraut Joellen J   Chang-Claude Jenny J   Burwinkel Barbara B   Chenevix-Trench Georgia G   Pharoah Paul D P PD   Berchuck Andrew A   Eeles Rosalind A RA   Easton Douglas F DF   Dunning Alison M AM   Nordestgaard Børge G BG  

Human molecular genetics 20130729 24


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 (  ...[more]

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