title: 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.
authors.affiliation: Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Pooley
authors.forename: Stig E
authors.initials: SE
authors.lastname: Bojesen
authors.forename: Maren
authors.initials: M
authors.lastname: Weischer
authors.forename: Sune F
authors.initials: SF
authors.lastname: Nielsen
authors.forename: Deborah
authors.initials: D
authors.lastname: Thompson
authors.forename: Ali
authors.initials: A
authors.lastname: Amin Al Olama
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Michailidou
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Tyrer
authors.forename: Sara
authors.initials: S
authors.lastname: Benlloch
authors.forename: Judith
authors.initials: J
authors.lastname: Brown
authors.forename: Tina
authors.initials: T
authors.lastname: Audley
authors.forename: Robert
authors.initials: R
authors.lastname: Luben
authors.forename: K-T
authors.initials: KT
authors.lastname: Khaw
authors.forename: David E
authors.initials: DE
authors.lastname: Neal
authors.forename: Freddie C
authors.initials: FC
authors.lastname: Hamdy
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Donovan
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Caroline
authors.initials: C
authors.lastname: Baynes
authors.forename: Mitul
authors.initials: M
authors.lastname: Shah
authors.forename: Manjeet K
authors.initials: MK
authors.lastname: Bolla
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Joe
authors.initials: J
authors.lastname: Dennis
authors.forename: Ed
authors.initials: E
authors.lastname: Dicks
authors.forename: Rongxi
authors.initials: R
authors.lastname: Yang
authors.forename: Anja
authors.initials: A
authors.lastname: Rudolph
authors.forename: Joellen
authors.initials: J
authors.lastname: Schildkraut
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Barbara
authors.initials: B
authors.lastname: Burwinkel
authors.forename: Georgia
authors.initials: G
authors.lastname: Chenevix-Trench
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
authors.forename: Andrew
authors.initials: A
authors.lastname: Berchuck
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Børge G
authors.initials: BG
authors.lastname: Nordestgaard
mesh_terms: D016022:Case-Control Studies; D002874:Chromosome Mapping; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059505:Telomere Homeostasis / Q000235:genetics*
references.citation: PLoS Med. 2012;9(5):e1001212
references.pmid: 22563304
references.citation: Nature. 2012 Nov 1;491(7422):56-65
references.pmid: 23128226
references.citation: Int J Epidemiol. 2003 Feb;32(1):1-22
references.pmid: 12689998
references.citation: Hum Mol Genet. 2012 Dec 15;21(24):5385-94
references.pmid: 23001564
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Apr;18(4):1152-6
references.pmid: 19293310
references.citation: Am J Hum Genet. 2006 Mar;78(3):480-6
references.pmid: 16400618
references.citation: Cancer Epidemiol Biomarkers Prev. 2011 Jun;20(6):1238-50
references.pmid: 21467229
references.citation: Int J Cancer. 2009 Apr 1;124(7):1637-43
references.pmid: 19089916
references.citation: Am J Hum Genet. 1994 Nov;55(5):876-82
references.pmid: 7977349
references.citation: Arterioscler Thromb Vasc Biol. 2012 Mar;32(3):822-9
references.pmid: 22199369
references.citation: J Natl Cancer Inst. 2011 Mar 16;103(6):508-19
references.pmid: 21285406
references.citation: J Natl Cancer Inst. 2013 Apr 3;105(7):459-68
references.pmid: 23468462
references.citation: J Mol Biol. 1992 Jun 20;225(4):951-60
references.pmid: 1613801
references.citation: J Clin Oncol. 2009 May 1;27(13):2217-24
references.pmid: 19289618
references.citation: Nat Genet. 2010 Mar;42(3):197-9
references.pmid: 20139977
references.citation: BMJ. 2002 Oct 5;325(7367):766-70
references.pmid: 12364308
references.citation: Nat Genet. 2013 Apr;45(4):353-61, 361e1-2
references.pmid: 23535729
references.citation: Proc Natl Acad Sci U S A. 2010 May 18;107(20):9293-8
references.pmid: 20421499
references.citation: J Natl Cancer Inst. 2010 Feb 3;102(3):202-6
references.pmid: 20056955
references.citation: N Engl J Med. 2008 Oct 30;359(18):1897-908
references.pmid: 18971492
references.citation: Cancer Epidemiol Biomarkers Prev. 2007 Apr;16(4):815-9
references.pmid: 17416776
references.citation: Nat Genet. 2013 Apr;45(4):371-84, 384e1-2
references.pmid: 23535731
references.citation: Nucleic Acids Res. 2002 May 15;30(10):e47
references.pmid: 12000852
references.citation: Nucleic Acids Res. 2009 Feb;37(3):e21
references.pmid: 19129229
references.citation: Hum Mol Genet. 2013 Jun 15;22(12):2520-8
references.pmid: 23535824
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Jul;19(7):1862-5
references.pmid: 20570912
references.citation: Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12135-9
references.pmid: 17623782
references.citation: Nat Genet. 2013 Apr;45(4):385-91, 391e1-2
references.pmid: 23535732
references.citation: Nat Genet. 2010 Jul;42(7):604-7
references.pmid: 20543847
references.citation: Mutat Res. 1991 Mar-Nov;256(2-6):271-82
references.pmid: 1722017
references.citation: Proc Natl Acad Sci U S A. 1988 Sep;85(18):6622-6
references.pmid: 3413114
references.citation: Philos Trans R Soc Lond B Biol Sci. 2004 Jan 29;359(1441):109-21
references.pmid: 15065663
references.citation: Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10114-8
references.pmid: 1438199
references.citation: Nat Genet. 2013 Apr;45(4):422-7, 427e1-2
references.pmid: 23535734
references.citation: Nat Genet. 2009 Aug;41(8):909-14
references.pmid: 19578363
references.citation: Nat Genet. 2013 Apr;45(4):362-70, 370e1-2
references.pmid: 23535730
references.citation: Cancer Res. 2010 Apr 15;70(8):3170-6
references.pmid: 20395204
references.citation: Cancer Epidemiol Biomarkers Prev. 2009 Aug;18(8):2280-2
references.pmid: 19661087
references.citation: Br J Cancer. 2005 Jul 11;93(1):167-71
references.pmid: 15970922
references.citation: Exp Gerontol. 2006 Dec;41(12):1223-7
references.pmid: 17084054
references.citation: Nat Genet. 2009 Feb;41(2):221-7
references.pmid: 19151717
references.citation: PLoS One. 2011 May 10;6(5):e19635
references.pmid: 21573004
references.citation: PLoS Genet. 2013;9(3):e1003212
references.pmid: 23544013
references.citation: Nature. 1990 May 31;345(6274):458-60
references.pmid: 2342578
references.citation: PLoS Genet. 2013;9(3):e1003173
references.pmid: 23544012