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Published in: Breast Cancer Research and Treatment 3/2011

01-04-2011 | Epidemiology

A combined analysis of genome-wide association studies in breast cancer

Authors: Jingmei Li, Keith Humphreys, Tuomas Heikkinen, Kristiina Aittomäki, Carl Blomqvist, Paul D. P. Pharoah, Alison M. Dunning, Shahana Ahmed, Maartje J. Hooning, John W. M. Martens, Ans M. W. van den Ouweland, Lars Alfredsson, Aarno Palotie, Leena Peltonen-Palotie, Astrid Irwanto, Hui Qi Low, Garrett H. K. Teoh, Anbupalam Thalamuthu, Douglas F. Easton, Heli Nevanlinna, Jianjun Liu, Kamila Czene, Per Hall

Published in: Breast Cancer Research and Treatment | Issue 3/2011

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Abstract

In an attempt to identify common disease susceptibility alleles for breast cancer, we performed a combined analysis of three genome-wide association studies (GWAS), involving 2,702 women of European ancestry with invasive breast cancer and 5,726 controls. Tests for association were performed for 285,984 SNPs. Evidence for association with SNPs in genes in specific pathways was assessed using a permutation-based approach. We confirmed associations with loci reported by previous GWAS on 1p11.2, 2q35, 3p, 5p12, 8q24, 10q23.13, 14q24.1 and 16q. Six SNPs with the strongest signals of association with breast cancer, and which have not been reported previously, were typed in two further studies; however, none of the associations could be confirmed. Suggestive evidence for an excess of associations was found for genes involved in the regulation of actin cytoskeleton, glycan degradation, alpha-linolenic acid metabolism, circadian rhythm, hematopoietic cell lineage and drug metabolism. Androgen and oestrogen metabolism, a pathway previously found to be associated with the development of postmenopausal breast cancer, was marginally significant (P = 0.051 [unadjusted]). These results suggest that further analysis of SNPs in these pathways may identify associations that would be difficult to detect through agnostic single SNP analyses. More effort focused in these aspects of oncology can potentially open up promising avenues for the understanding of breast cancer and its prevention.
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Literature
1.
go back to reference Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, Johnson N, Seal S, Stratton MR, Rahman N, Chenevix-Trench G, Bojesen SE, Nordestgaard BG, Axelsson CK, Garcia-Closas M, Brinton L, Chanock S, Lissowska J, Peplonska B, Nevanlinna H, Fagerholm R, Eerola H, Kang D, Yoo KY, Noh DY, Ahn SH, Hunter DJ, Hankinson SE, Cox DG, Hall P, Wedren S, Liu J, Low YL, Bogdanova N, Schurmann P, Dork T, Tollenaar RA, Jacobi CE, Devilee P, Klijn JG, Sigurdson AJ, Doody MM, Alexander BH, Zhang J, Cox A, Brock IW, MacPherson G, Reed MW, Couch FJ, Goode EL, Olson JE, Meijers-Heijboer H, van den Ouweland A, Uitterlinden A, Rivadeneira F, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Hopper JL, McCredie M, Southey M, Giles GG, Schroen C, Justenhoven C, Brauch H, Hamann U, Ko YD, Spurdle AB, Beesley J, Chen X, Mannermaa A, Kosma VM, Kataja V, Hartikainen J, Day NE, Cox DR, Ponder BA (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447(7148):1087–1093. doi:10.1038/nature05887 PubMedCrossRef Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R, Wareham N, Ahmed S, Healey CS, Bowman R, Meyer KB, Haiman CA, Kolonel LK, Henderson BE, Le Marchand L, Brennan P, Sangrajrang S, Gaborieau V, Odefrey F, Shen CY, Wu PE, Wang HC, Eccles D, Evans DG, Peto J, Fletcher O, Johnson N, Seal S, Stratton MR, Rahman N, Chenevix-Trench G, Bojesen SE, Nordestgaard BG, Axelsson CK, Garcia-Closas M, Brinton L, Chanock S, Lissowska J, Peplonska B, Nevanlinna H, Fagerholm R, Eerola H, Kang D, Yoo KY, Noh DY, Ahn SH, Hunter DJ, Hankinson SE, Cox DG, Hall P, Wedren S, Liu J, Low YL, Bogdanova N, Schurmann P, Dork T, Tollenaar RA, Jacobi CE, Devilee P, Klijn JG, Sigurdson AJ, Doody MM, Alexander BH, Zhang J, Cox A, Brock IW, MacPherson G, Reed MW, Couch FJ, Goode EL, Olson JE, Meijers-Heijboer H, van den Ouweland A, Uitterlinden A, Rivadeneira F, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Hopper JL, McCredie M, Southey M, Giles GG, Schroen C, Justenhoven C, Brauch H, Hamann U, Ko YD, Spurdle AB, Beesley J, Chen X, Mannermaa A, Kosma VM, Kataja V, Hartikainen J, Day NE, Cox DR, Ponder BA (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447(7148):1087–1093. doi:10.​1038/​nature05887 PubMedCrossRef
2.
go back to reference Ahmed S, Thomas G, Ghoussaini M, Healey CS, Humphreys MK, Platte R, Morrison J, Maranian M, Pooley KA, Luben R, Eccles D, Evans DG, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Stratton MR, Rahman N, Jacobs K, Prentice R, Anderson GL, Rajkovic A, Curb JD, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver WR, Bojesen S, Nordestgaard BG, Flyger H, Dork T, Schurmann P, Hillemanns P, Karstens JH, Bogdanova NV, Antonenkova NN, Zalutsky IV, Bermisheva M, Fedorova S, Khusnutdinova E, Kang D, Yoo KY, Noh DY, Ahn SH, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Garcia-Closas M, Lissowska J, Brinton L, Peplonska B, Nevanlinna H, Heikkinen T, Aittomaki K, Blomqvist C, Hopper JL, Southey MC, Smith L, Spurdle AB, Schmidt MK, Broeks A, van Hien RR, Cornelissen S, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Schmutzler RK, Burwinkel B, Bartram CR, Meindl A, Brauch H, Justenhoven C, Hamann U, Chang-Claude J, Hein R, Wang-Gohrke S, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Kataja V, Olson JE, Wang X, Fredericksen Z, Giles GG, Severi G, Baglietto L, English DR, Hankinson SE, Cox DG, Kraft P, Vatten LJ, Hveem K, Kumle M, Sigurdson A, Doody M, Bhatti P, Alexander BH, Hooning MJ, van den Ouweland AM, Oldenburg RA, Schutte M, Hall P, Czene K, Liu J, Li Y, Cox A, Elliott G, Brock I, Reed MW, Shen CY, Yu JC, Hsu GC, Chen ST, Anton-Culver H, Ziogas A, Andrulis IL, Knight JA, Beesley J, Goode EL, Couch F, Chenevix-Trench G, Hoover RN, Ponder BA, Hunter DJ, Pharoah PD, Dunning AM, Chanock SJ, Easton DF (2009) Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet 41(5):585–590. doi:10.1038/ng.354 Ahmed S, Thomas G, Ghoussaini M, Healey CS, Humphreys MK, Platte R, Morrison J, Maranian M, Pooley KA, Luben R, Eccles D, Evans DG, Fletcher O, Johnson N, dos Santos Silva I, Peto J, Stratton MR, Rahman N, Jacobs K, Prentice R, Anderson GL, Rajkovic A, Curb JD, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver WR, Bojesen S, Nordestgaard BG, Flyger H, Dork T, Schurmann P, Hillemanns P, Karstens JH, Bogdanova NV, Antonenkova NN, Zalutsky IV, Bermisheva M, Fedorova S, Khusnutdinova E, Kang D, Yoo KY, Noh DY, Ahn SH, Devilee P, van Asperen CJ, Tollenaar RA, Seynaeve C, Garcia-Closas M, Lissowska J, Brinton L, Peplonska B, Nevanlinna H, Heikkinen T, Aittomaki K, Blomqvist C, Hopper JL, Southey MC, Smith L, Spurdle AB, Schmidt MK, Broeks A, van Hien RR, Cornelissen S, Milne RL, Ribas G, Gonzalez-Neira A, Benitez J, Schmutzler RK, Burwinkel B, Bartram CR, Meindl A, Brauch H, Justenhoven C, Hamann U, Chang-Claude J, Hein R, Wang-Gohrke S, Lindblom A, Margolin S, Mannermaa A, Kosma VM, Kataja V, Olson JE, Wang X, Fredericksen Z, Giles GG, Severi G, Baglietto L, English DR, Hankinson SE, Cox DG, Kraft P, Vatten LJ, Hveem K, Kumle M, Sigurdson A, Doody M, Bhatti P, Alexander BH, Hooning MJ, van den Ouweland AM, Oldenburg RA, Schutte M, Hall P, Czene K, Liu J, Li Y, Cox A, Elliott G, Brock I, Reed MW, Shen CY, Yu JC, Hsu GC, Chen ST, Anton-Culver H, Ziogas A, Andrulis IL, Knight JA, Beesley J, Goode EL, Couch F, Chenevix-Trench G, Hoover RN, Ponder BA, Hunter DJ, Pharoah PD, Dunning AM, Chanock SJ, Easton DF (2009) Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2. Nat Genet 41(5):585–590. doi:10.​1038/​ng.​354
3.
go back to reference Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Thomas G, Chanock SJ (2007) A genome-wide association study identifies alleles in fgfr2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39(7):870–874. doi:10.1038/ng2075 PubMedCrossRef Hunter DJ, Kraft P, Jacobs KB, Cox DG, Yeager M, Hankinson SE, Wacholder S, Wang Z, Welch R, Hutchinson A, Wang J, Yu K, Chatterjee N, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF Jr, Hoover RN, Thomas G, Chanock SJ (2007) A genome-wide association study identifies alleles in fgfr2 associated with risk of sporadic postmenopausal breast cancer. Nat Genet 39(7):870–874. doi:10.​1038/​ng2075 PubMedCrossRef
4.
go back to reference Thomas G, Jacobs KB, Kraft P, Yeager M, Wacholder S, Cox DG, Hankinson SE, Hutchinson A, Wang Z, Yu K, Chatterjee N, Garcia-Closas M, Gonzalez-Bosquet J, Prokunina-Olsson L, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver R, Prentice R, Jackson R, Kooperberg C, Chlebowski R, Lissowska J, Peplonska B, Brinton LA, Sigurdson A, Doody M, Bhatti P, Alexander BH, Buring J, Lee IM, Vatten LJ, Hveem K, Kumle M, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF, Jr., Hoover RN, Chanock SJ, Hunter DJ (2009) A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (rad51l1). Nat Genet 41(5):579–584. doi:10.1038/ng.353 Thomas G, Jacobs KB, Kraft P, Yeager M, Wacholder S, Cox DG, Hankinson SE, Hutchinson A, Wang Z, Yu K, Chatterjee N, Garcia-Closas M, Gonzalez-Bosquet J, Prokunina-Olsson L, Orr N, Willett WC, Colditz GA, Ziegler RG, Berg CD, Buys SS, McCarty CA, Feigelson HS, Calle EE, Thun MJ, Diver R, Prentice R, Jackson R, Kooperberg C, Chlebowski R, Lissowska J, Peplonska B, Brinton LA, Sigurdson A, Doody M, Bhatti P, Alexander BH, Buring J, Lee IM, Vatten LJ, Hveem K, Kumle M, Hayes RB, Tucker M, Gerhard DS, Fraumeni JF, Jr., Hoover RN, Chanock SJ, Hunter DJ (2009) A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (rad51l1). Nat Genet 41(5):579–584. doi:10.​1038/​ng.​353
5.
go back to reference Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, Gudjonsson SA, Masson G, Jakobsdottir M, Thorlacius S, Helgason A, Aben KK, Strobbe LJ, Albers-Akkers MT, Swinkels DW, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Godino J, Garcia-Prats MD, Polo E, Tres A, Mouy M, Saemundsdottir J, Backman VM, Gudmundsson L, Kristjansson K, Bergthorsson JT, Kostic J, Frigge ML, Geller F, Gudbjartsson D, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Jonsson T, von Holst S, Werelius B, Margolin S, Lindblom A, Mayordomo JI, Haiman CA, Kiemeney LA, Johannsson OT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2007) Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39(7):865–869. doi:10.1038/ng2064 PubMedCrossRef Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, Gudjonsson SA, Masson G, Jakobsdottir M, Thorlacius S, Helgason A, Aben KK, Strobbe LJ, Albers-Akkers MT, Swinkels DW, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Godino J, Garcia-Prats MD, Polo E, Tres A, Mouy M, Saemundsdottir J, Backman VM, Gudmundsson L, Kristjansson K, Bergthorsson JT, Kostic J, Frigge ML, Geller F, Gudbjartsson D, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Jonsson T, von Holst S, Werelius B, Margolin S, Lindblom A, Mayordomo JI, Haiman CA, Kiemeney LA, Johannsson OT, Gulcher JR, Thorsteinsdottir U, Kong A, Stefansson K (2007) Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39(7):865–869. doi:10.​1038/​ng2064 PubMedCrossRef
6.
go back to reference Stacey SN, Manolescu A, Sulem P, Thorlacius S, Gudjonsson SA, Jonsson GF, Jakobsdottir M, Bergthorsson JT, Gudmundsson J, Aben KK, Strobbe LJ, Swinkels DW, van Engelenburg KC, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Saez B, Lambea J, Godino J, Polo E, Tres A, Picelli S, Rantala J, Margolin S, Jonsson T, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Sveinsdottir SG, Alexiusdottir K, Saemundsdottir J, Sigurdsson A, Kostic J, Gudmundsson L, Kristjansson K, Masson G, Fackenthal JD, Adebamowo C, Ogundiran T, Olopade OI, Haiman CA, Lindblom A, Mayordomo JI, Kiemeney LA, Gulcher JR, Rafnar T, Thorsteinsdottir U, Johannsson OT, Kong A, Stefansson K (2008) Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40(6):703–706. doi:10.1038/ng.131 PubMedCrossRef Stacey SN, Manolescu A, Sulem P, Thorlacius S, Gudjonsson SA, Jonsson GF, Jakobsdottir M, Bergthorsson JT, Gudmundsson J, Aben KK, Strobbe LJ, Swinkels DW, van Engelenburg KC, Henderson BE, Kolonel LN, Le Marchand L, Millastre E, Andres R, Saez B, Lambea J, Godino J, Polo E, Tres A, Picelli S, Rantala J, Margolin S, Jonsson T, Sigurdsson H, Jonsdottir T, Hrafnkelsson J, Johannsson J, Sveinsson T, Myrdal G, Grimsson HN, Sveinsdottir SG, Alexiusdottir K, Saemundsdottir J, Sigurdsson A, Kostic J, Gudmundsson L, Kristjansson K, Masson G, Fackenthal JD, Adebamowo C, Ogundiran T, Olopade OI, Haiman CA, Lindblom A, Mayordomo JI, Kiemeney LA, Gulcher JR, Rafnar T, Thorsteinsdottir U, Johannsson OT, Kong A, Stefansson K (2008) Common variants on chromosome 5p12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 40(6):703–706. doi:10.​1038/​ng.​131 PubMedCrossRef
7.
go back to reference Zheng W, Long J, Gao YT, Li C, Zheng Y, Xiang YB, Wen W, Levy S, Deming SL, Haines JL, Gu K, Fair AM, Cai Q, Lu W, Shu XO (2009) Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41(3):324–328. doi:10.1038/ng.318 PubMedCrossRef Zheng W, Long J, Gao YT, Li C, Zheng Y, Xiang YB, Wen W, Levy S, Deming SL, Haines JL, Gu K, Fair AM, Cai Q, Lu W, Shu XO (2009) Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1. Nat Genet 41(3):324–328. doi:10.​1038/​ng.​318 PubMedCrossRef
9.
go back to reference Peng G, Luo L, Siu H, Zhu Y, Hu P, Hong S, Zhao J, Zhou X, Reveille JD, Jin L, Amos CI, Xiong M (2009) Gene and pathway-based second-wave analysis of genome-wide association studies. Eur J Hum Genet. doi:10.1038/ejhg.2009.115 Peng G, Luo L, Siu H, Zhu Y, Hu P, Hong S, Zhao J, Zhou X, Reveille JD, Jin L, Amos CI, Xiong M (2009) Gene and pathway-based second-wave analysis of genome-wide association studies. Eur J Hum Genet. doi:10.​1038/​ejhg.​2009.​115
10.
go back to reference Wang K, Li M, Bucan M (2007) Pathway-based approaches for analysis of genomewide association studies. Am J Hum Genet 81(6). doi:10.1086/522374 Wang K, Li M, Bucan M (2007) Pathway-based approaches for analysis of genomewide association studies. Am J Hum Genet 81(6). doi:10.​1086/​522374
12.
13.
go back to reference Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, Liew A, Khalili H, Chandrasekaran A, Davies LR, Li W, Tan AK, Bonnard C, Ong RT, Thalamuthu A, Pettersson S, Liu C, Tian C, Chen WV, Carulli JP, Beckman EM, Altshuler D, Alfredsson L, Criswell LA, Amos CI, Seldin MF, Kastner DL, Klareskog L, Gregersen PK (2007) Traf1-c5 as a risk locus for rheumatoid arthritis—a genomewide study. N Engl J Med 357(12):1199–1209. doi:10.1056/NEJMoa073491 PubMedCrossRef Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, Liew A, Khalili H, Chandrasekaran A, Davies LR, Li W, Tan AK, Bonnard C, Ong RT, Thalamuthu A, Pettersson S, Liu C, Tian C, Chen WV, Carulli JP, Beckman EM, Altshuler D, Alfredsson L, Criswell LA, Amos CI, Seldin MF, Kastner DL, Klareskog L, Gregersen PK (2007) Traf1-c5 as a risk locus for rheumatoid arthritis—a genomewide study. N Engl J Med 357(12):1199–1209. doi:10.​1056/​NEJMoa073491 PubMedCrossRef
14.
go back to reference Bilguvar K, Yasuno K, Niemela M, Ruigrok YM, von Und Zu Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaal E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Ohman J, Breteler MM, Wijmenga C, State MW, Rinkel GJ, Hernesniemi J, Jaaskelainen JE, Palotie A, Inoue I, Lifton RP, Gunel M (2008) Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet 40(12):1472–1477. doi:10.1038/ng.240 PubMedCrossRef Bilguvar K, Yasuno K, Niemela M, Ruigrok YM, von Und Zu Fraunberg M, van Duijn CM, van den Berg LH, Mane S, Mason CE, Choi M, Gaal E, Bayri Y, Kolb L, Arlier Z, Ravuri S, Ronkainen A, Tajima A, Laakso A, Hata A, Kasuya H, Koivisto T, Rinne J, Ohman J, Breteler MM, Wijmenga C, State MW, Rinkel GJ, Hernesniemi J, Jaaskelainen JE, Palotie A, Inoue I, Lifton RP, Gunel M (2008) Susceptibility loci for intracranial aneurysm in European and Japanese populations. Nat Genet 40(12):1472–1477. doi:10.​1038/​ng.​240 PubMedCrossRef
15.
go back to reference Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, Penninx BW, Janssens AC, Wilson JF, Spector T, Martin NG, Pedersen NL, Kyvik KO, Kaprio J, Hofman A, Freimer NB, Jarvelin MR, Gyllensten U, Campbell H, Rudan I, Johansson A, Marroni F, Hayward C, Vitart V, Jonasson I, Pattaro C, Wright A, Hastie N, Pichler I, Hicks AA, Falchi M, Willemsen G, Hottenga JJ, de Geus EJ, Montgomery GW, Whitfield J, Magnusson P, Saharinen J, Perola M, Silander K, Isaacs A, Sijbrands EJ, Uitterlinden AG, Witteman JC, Oostra BA, Elliott P, Ruokonen A, Sabatti C, Gieger C, Meitinger T, Kronenberg F, Doring A, Wichmann HE, Smit JH, McCarthy MI, van Duijn CM, Peltonen L (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 41(1):47–55. doi:10.1038/ng.269 PubMedCrossRef Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, Pramstaller PP, Penninx BW, Janssens AC, Wilson JF, Spector T, Martin NG, Pedersen NL, Kyvik KO, Kaprio J, Hofman A, Freimer NB, Jarvelin MR, Gyllensten U, Campbell H, Rudan I, Johansson A, Marroni F, Hayward C, Vitart V, Jonasson I, Pattaro C, Wright A, Hastie N, Pichler I, Hicks AA, Falchi M, Willemsen G, Hottenga JJ, de Geus EJ, Montgomery GW, Whitfield J, Magnusson P, Saharinen J, Perola M, Silander K, Isaacs A, Sijbrands EJ, Uitterlinden AG, Witteman JC, Oostra BA, Elliott P, Ruokonen A, Sabatti C, Gieger C, Meitinger T, Kronenberg F, Doring A, Wichmann HE, Smit JH, McCarthy MI, van Duijn CM, Peltonen L (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 41(1):47–55. doi:10.​1038/​ng.​269 PubMedCrossRef
16.
go back to reference Sabatti C, Service SK, Hartikainen AL, Pouta A, Ripatti S, Brodsky J, Jones CG, Zaitlen NA, Varilo T, Kaakinen M, Sovio U, Ruokonen A, Laitinen J, Jakkula E, Coin L, Hoggart C, Collins A, Turunen H, Gabriel S, Elliot P, McCarthy MI, Daly MJ, Jarvelin MR, Freimer NB, Peltonen L (2009) Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet 41(1):35–46. doi:10.1038/ng.271 PubMedCrossRef Sabatti C, Service SK, Hartikainen AL, Pouta A, Ripatti S, Brodsky J, Jones CG, Zaitlen NA, Varilo T, Kaakinen M, Sovio U, Ruokonen A, Laitinen J, Jakkula E, Coin L, Hoggart C, Collins A, Turunen H, Gabriel S, Elliot P, McCarthy MI, Daly MJ, Jarvelin MR, Freimer NB, Peltonen L (2009) Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet 41(1):35–46. doi:10.​1038/​ng.​271 PubMedCrossRef
17.
go back to reference Leu M, Humphreys K, Surakka I, Rehnberg E, Muilu J, Rosenstrom P, Almgren P, Jaaskelainen J, Lifton RP, Kyvik KO, Kaprio J, Pedersen NL, Palotie A, Hall P, Gronberg H, Groop L, Peltonen L, Palmgren J, Ripatti S (2010) NordicDB: a nordic pool and portal for genome-wide control data. Eur J Hum Genet. doi:10.1038/ejhg.2010.112 Leu M, Humphreys K, Surakka I, Rehnberg E, Muilu J, Rosenstrom P, Almgren P, Jaaskelainen J, Lifton RP, Kyvik KO, Kaprio J, Pedersen NL, Palotie A, Hall P, Gronberg H, Groop L, Peltonen L, Palmgren J, Ripatti S (2010) NordicDB: a nordic pool and portal for genome-wide control data. Eur J Hum Genet. doi:10.​1038/​ejhg.​2010.​112
18.
go back to reference Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies il23r as an inflammatory bowel disease gene. Science 314(5804):1461–1463. doi:10.1126/science.1135245 PubMedCrossRef Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies il23r as an inflammatory bowel disease gene. Science 314(5804):1461–1463. doi:10.​1126/​science.​1135245 PubMedCrossRef
19.
go back to reference Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) Plink: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi:10.1086/519795 PubMedCrossRef Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC (2007) Plink: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi:10.​1086/​519795 PubMedCrossRef
20.
go back to reference Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38(8):904–909. doi:10.1038/ng1847 PubMedCrossRef Price AL, Patterson NJ, Plenge RM, Weinblatt ME, Shadick NA, Reich D (2006) Principal components analysis corrects for stratification in genome-wide association studies. Nat Genet 38(8):904–909. doi:10.​1038/​ng1847 PubMedCrossRef
22.
go back to reference Kanehisa M, Goto S (2000) Kegg: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30PubMedCrossRef Kanehisa M, Goto S (2000) Kegg: Kyoto encyclopedia of genes and genomes. Nucleic Acids Res 28(1):27–30PubMedCrossRef
25.
go back to reference R Development Core Team (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria R Development Core Team (2008) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna, Austria
27.
go back to reference Cheng D, Knox C, Young N, Stothard P, Damaraju S, Wishart DS (2008) Polysearch: a web-based text mining system for extracting relationships between human diseases, genes, mutations, drugs and metabolites. Nucleic Acids Res 36(Web Server issue):W399–W405. doi:10.1093/nar/gkn296 Cheng D, Knox C, Young N, Stothard P, Damaraju S, Wishart DS (2008) Polysearch: a web-based text mining system for extracting relationships between human diseases, genes, mutations, drugs and metabolites. Nucleic Acids Res 36(Web Server issue):W399–W405. doi:10.​1093/​nar/​gkn296
28.
29.
go back to reference Lesueur F, Pharoah PD, Laing S, Ahmed S, Jordan C, Smith PL, Luben R, Wareham NJ, Easton DF, Dunning AM, Ponder BA (2005) Allelic association of the human homologue of the mouse modifier ptprj with breast cancer. Hum Mol Genet 14(16):2349–2356. doi:10.1093/hmg/ddi237 PubMedCrossRef Lesueur F, Pharoah PD, Laing S, Ahmed S, Jordan C, Smith PL, Luben R, Wareham NJ, Easton DF, Dunning AM, Ponder BA (2005) Allelic association of the human homologue of the mouse modifier ptprj with breast cancer. Hum Mol Genet 14(16):2349–2356. doi:10.​1093/​hmg/​ddi237 PubMedCrossRef
30.
go back to reference Kiemeney LA, Thorlacius S, Sulem P, Geller F, Aben KK, Stacey SN, Gudmundsson J, Jakobsdottir M, Bergthorsson JT, Sigurdsson A, Blondal T, Witjes JA, Vermeulen SH, Hulsbergen-van de Kaa CA, Swinkels DW, Ploeg M, Cornel EB, Vergunst H, Thorgeirsson TE, Gudbjartsson D, Gudjonsson SA, Thorleifsson G, Kristinsson KT, Mouy M, Snorradottir S, Placidi D, Campagna M, Arici C, Koppova K, Gurzau E, Rudnai P, Kellen E, Polidoro S, Guarrera S, Sacerdote C, Sanchez M, Saez B, Valdivia G, Ryk C, de Verdier P, Lindblom A, Golka K, Bishop DT, Knowles MA, Nikulasson S, Petursdottir V, Jonsson E, Geirsson G, Kristjansson B, Mayordomo JI, Steineck G, Porru S, Buntinx F, Zeegers MP, Fletcher T, Kumar R, Matullo G, Vineis P, Kiltie AE, Gulcher JR, Thorsteinsdottir U, Kong A, Rafnar T, Stefansson K (2008) Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat Genet 40(11):1307–1312. doi:10.1038/ng.229 PubMedCrossRef Kiemeney LA, Thorlacius S, Sulem P, Geller F, Aben KK, Stacey SN, Gudmundsson J, Jakobsdottir M, Bergthorsson JT, Sigurdsson A, Blondal T, Witjes JA, Vermeulen SH, Hulsbergen-van de Kaa CA, Swinkels DW, Ploeg M, Cornel EB, Vergunst H, Thorgeirsson TE, Gudbjartsson D, Gudjonsson SA, Thorleifsson G, Kristinsson KT, Mouy M, Snorradottir S, Placidi D, Campagna M, Arici C, Koppova K, Gurzau E, Rudnai P, Kellen E, Polidoro S, Guarrera S, Sacerdote C, Sanchez M, Saez B, Valdivia G, Ryk C, de Verdier P, Lindblom A, Golka K, Bishop DT, Knowles MA, Nikulasson S, Petursdottir V, Jonsson E, Geirsson G, Kristjansson B, Mayordomo JI, Steineck G, Porru S, Buntinx F, Zeegers MP, Fletcher T, Kumar R, Matullo G, Vineis P, Kiltie AE, Gulcher JR, Thorsteinsdottir U, Kong A, Rafnar T, Stefansson K (2008) Sequence variant on 8q24 confers susceptibility to urinary bladder cancer. Nat Genet 40(11):1307–1312. doi:10.​1038/​ng.​229 PubMedCrossRef
31.
32.
go back to reference The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678. doi:10.1038/nature05911 The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678. doi:10.​1038/​nature05911
36.
go back to reference Chopra P, Shin HJ, Kang J (2008) Global gene map for cancer reveals pathway hotspots. In: Proceedings of the IEEE International conference on Bioinformatics and Biomedicine (BIBM), Philadelphia, USA Chopra P, Shin HJ, Kang J (2008) Global gene map for cancer reveals pathway hotspots. In: Proceedings of the IEEE International conference on Bioinformatics and Biomedicine (BIBM), Philadelphia, USA
37.
38.
go back to reference Low YL, Li Y, Humphreys K, Thalamuthu A, Darabi H, Wedren S, Bonnard C, Czene K, Iles MM, Heikkinen T, Aittomaki K, Blomqvist C, Nevanlinna H, Hall P, Liu ET, Liu J (2010) Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility. PLoS Genet 6:e1001012. doi:10.1371/journal.pgen.1001012 Low YL, Li Y, Humphreys K, Thalamuthu A, Darabi H, Wedren S, Bonnard C, Czene K, Iles MM, Heikkinen T, Aittomaki K, Blomqvist C, Nevanlinna H, Hall P, Liu ET, Liu J (2010) Multi-variant pathway association analysis reveals the importance of genetic determinants of estrogen metabolism in breast and endometrial cancer susceptibility. PLoS Genet 6:e1001012. doi:10.​1371/​journal.​pgen.​1001012
39.
go back to reference Graham JD, Hunt SM, Tran N, Clarke CL (1999) Regulation of the expression and activity by progestins of a member of the sox gene family of transcriptional modulators. J Mol Endocrinol 22(3):295–304PubMedCrossRef Graham JD, Hunt SM, Tran N, Clarke CL (1999) Regulation of the expression and activity by progestins of a member of the sox gene family of transcriptional modulators. J Mol Endocrinol 22(3):295–304PubMedCrossRef
41.
go back to reference Curran JE, Weinstein SR, Griffiths LR (2002) Polymorphic variants of nfkb1 and its inhibitory protein nfkbia, and their involvement in sporadic breast cancer. Cancer Lett 188(1–2):103–107. doi:S0304383502004603[pii] PubMedCrossRef Curran JE, Weinstein SR, Griffiths LR (2002) Polymorphic variants of nfkb1 and its inhibitory protein nfkbia, and their involvement in sporadic breast cancer. Cancer Lett 188(1–2):103–107. doi:S030438350200460​3[pii] PubMedCrossRef
42.
go back to reference Yamashita S, Yamashita J, Sakamoto K, Inada K, Nakashima Y, Murata K, Saishoji T, Nomura K, Ogawa M (1993) Increased expression of membrane-associated phospholipase a2 shows malignant potential of human breast cancer cells. Cancer 71(10):3058–3064PubMedCrossRef Yamashita S, Yamashita J, Sakamoto K, Inada K, Nakashima Y, Murata K, Saishoji T, Nomura K, Ogawa M (1993) Increased expression of membrane-associated phospholipase a2 shows malignant potential of human breast cancer cells. Cancer 71(10):3058–3064PubMedCrossRef
43.
go back to reference Zhu Y, Stevens RG, Leaderer D, Hoffman A, Holford T, Zhang Y, Brown HN, Zheng T (2008) Non-synonymous polymorphisms in the circadian gene npas2 and breast cancer risk. Breast Cancer Res Treat 107(3):421–425. doi:10.1007/s10549-007-9565-0 PubMedCrossRef Zhu Y, Stevens RG, Leaderer D, Hoffman A, Holford T, Zhang Y, Brown HN, Zheng T (2008) Non-synonymous polymorphisms in the circadian gene npas2 and breast cancer risk. Breast Cancer Res Treat 107(3):421–425. doi:10.​1007/​s10549-007-9565-0 PubMedCrossRef
Metadata
Title
A combined analysis of genome-wide association studies in breast cancer
Authors
Jingmei Li
Keith Humphreys
Tuomas Heikkinen
Kristiina Aittomäki
Carl Blomqvist
Paul D. P. Pharoah
Alison M. Dunning
Shahana Ahmed
Maartje J. Hooning
John W. M. Martens
Ans M. W. van den Ouweland
Lars Alfredsson
Aarno Palotie
Leena Peltonen-Palotie
Astrid Irwanto
Hui Qi Low
Garrett H. K. Teoh
Anbupalam Thalamuthu
Douglas F. Easton
Heli Nevanlinna
Jianjun Liu
Kamila Czene
Per Hall
Publication date
01-04-2011
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-1172-9

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