Abstract
A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r 2=0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI =1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI =0.98-1.07, case-only P-heterogeneity =7.6 × 10 -5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P=6.7 × 10 -3) and lobular histology (case-only P=0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. Published by Oxford University Press 2011.
Original language | English |
---|---|
Article number | ddr368 |
Pages (from-to) | 4693-4706 |
Number of pages | 14 |
Journal | Human Molecular Genetics |
Volume | 20 |
Issue number | 23 |
DOIs | |
Publication status | Published - Dec 2011 |
Externally published | Yes |
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In: Human Molecular Genetics, Vol. 20, No. 23, ddr368, 12.2011, p. 4693-4706.
Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Associations of common variants at 1p11.2 and 14q24.1 (RAD51l1) with breast cancer risk and heterogeneity by tumor subtype
T2 - Findings from the Breast Cancer Association Consortium
AU - Figueroa, Jonine D
AU - Garcia-Closas, Montserrat
AU - Humphreys, Manjeet
AU - Platte, Radka
AU - Hopper, John L.
AU - Southey, Melissa C.
AU - Apicella, Carmel
AU - Hammet, Fleur
AU - Schmidt, Marjanka K.
AU - Broeks, Annegien
AU - Tollenaar, Rob A.E.M.
AU - Van't Veer, Laura J.
AU - Fasching, Peter A.
AU - Beckmann, Matthias W.
AU - Ekici, Arif B
AU - Strick, Reiner
AU - Peto, Julian
AU - Silva, Isabel Dos Santos
AU - Fletcher, Olivia
AU - Johnson, Nichola
AU - Sawyer, Elinor J
AU - Tomlinson, Ian P
AU - Kerin, Michael
AU - Burwinkel, Barbara
AU - Marme, Federik
AU - Schneeweiss, Andreas
AU - Sohn, Christof
AU - Bojesen, Stig E
AU - Flyger, Henrik
AU - Nordestgaard, Børge G.
AU - Benítez, Javier
AU - Milne, Roger L
AU - Arias, Jose Ignacio
AU - Zamora, Pilar M.
AU - Brenner, Hermann
AU - Müller, Heiko
AU - Arndt, Volker
AU - Rahman, Nazneen
AU - Turnbull, Clare
AU - Seal, Sheila
AU - Renwick, Anthony
AU - Brauch, Hiltrud
AU - Justenhoven, Christina
AU - Brüning, Thomas
AU - Ko, Yon-Dschun
AU - Baisch, Christian
AU - Fischer, Hand Peter
AU - Hamann, Ute
AU - Pesch, Beate
AU - Rabstein, Sylvia
AU - Harth, Volker
AU - Chang-Claude, Jenny
AU - Hein, Rebecca
AU - Wang-Gohrke, Shan
AU - Dörk, Thilo
AU - Schürmann, Peter
AU - Bremer, Michael
AU - Hillemanns, Peter
AU - Nevanlinna, Heli
AU - Heikkinen, Tuomas
AU - Aittomäki, Kristiina
AU - Blomqvist, Carl
AU - Bogdanova, Natalia
AU - Antonenkova, Natalia
AU - Rogov, Yuri I.
AU - Karstens, Johann Hinrich
AU - Bermisheva, Marina
AU - Prokofieva, Darya
AU - Gantcev, Shamil Hanafievich
AU - Khusnutdinova, Elza
AU - Lindblom, Annika
AU - Margolin, Sara
AU - Chenevix-Trench, Georgia
AU - Beesley, Jonathan
AU - Chen, Xiaoqing
AU - Bowtell, David D L
AU - Chenevix-Trench, Georgia
AU - DeFazio, Anna
AU - Gertig, Dorota M
AU - Green, A.
AU - Webb, Penelope M
AU - Mannermaa, Arto
AU - Kosma, Veli-Matti
AU - Soini, Ylermi
AU - Kataja, Vesa
AU - Lambrechts, Diether
AU - Yesilyurt, Betül T.
AU - Chrisiaens, Marie Rose
AU - Peeters, Stephanie
AU - Radice, Paolo
AU - Peterlongo, Paolo
AU - Manoukian, Siranoush
AU - Barile, Monica
AU - Couch, Fergus J
AU - Lee, Adam M.
AU - Diasio, Robert B.
AU - Wang, Xianshu
AU - Giles, Graham G.
AU - Severi, Gianluca
AU - Baglietto, Laura
AU - Maclean, Catriona
AU - Offit, Ken
AU - Robson, Mark E
AU - Joseph, Vijai
AU - Gaudet, Mia M
AU - John, Esther M.
AU - Winqvist, Robert
AU - Pylkäs, Katri
AU - Jukkola-Vuorinen, Arja
AU - Grip, Mervi
AU - Andrulis, Irene L
AU - Knight, Julia A
AU - Mulligan, Anna Marie
AU - O'Malley, Frances P
AU - Brinton, Louise A.
AU - Sherman, Mark E
AU - Lissowska, Jolanta
AU - Chanock, Stephen J
AU - Hooning, Maartje J
AU - Martens, John W M
AU - van den Ouweland, Ans M W
AU - Collée, Johanna Margriet
AU - Hall, Per
AU - Czene, Kamila
AU - Cox, Angela
AU - Brock, Ian W.
AU - Reed, Malcolm W R
AU - Cross, Simon S
AU - Pharoah, Paul D P
AU - Dunning, Alison M
AU - Kang, Daehee
AU - Yoo, Keun-Young
AU - Noh, Dong-Young
AU - Ahn, Sei Hyun
AU - Jakubowska, Anna
AU - Lubinski, Jan
AU - Jaworska, Katarzyna
AU - Durda, Katarzyna
AU - Sangrajrang, Suleeporn
AU - Gaborieau, Valerie
AU - Brennan, Paul
AU - McKay, James
AU - Shen, Chen-Yang
AU - Ding, Shian Ling
AU - Hsu, Huan Ming
AU - Yu, Jyh-Cherng
AU - Anton-Culver, Hoda
AU - Ziogas, Argyrios
AU - Ashworth, Alan
AU - Swerdlow, Anthony J
AU - Jones, Michael
AU - Orr, Nick
AU - Trentham-Dietz, Amy
AU - Egan, Kathleen
AU - Newcomb, Polly A
AU - Titus-Ernstoff, Linda
AU - Easton, Doug
AU - Spurdle, Amanda B
PY - 2011/12
Y1 - 2011/12
N2 - A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r 2=0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI =1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI =0.98-1.07, case-only P-heterogeneity =7.6 × 10 -5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P=6.7 × 10 -3) and lobular histology (case-only P=0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. Published by Oxford University Press 2011.
AB - A genome-wide association study (GWAS) identified single-nucleotide polymorphisms (SNPs) at 1p11.2 and 14q24.1 (RAD51L1) as breast cancer susceptibility loci. The initial GWAS suggested stronger effects for both loci for estrogen receptor (ER)-positive tumors. Using data from the Breast Cancer Association Consortium (BCAC), we sought to determine whether risks differ by ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), grade, node status, tumor size, and ductal or lobular morphology. We genotyped rs11249433 at 1p.11.2, and two highly correlated SNPs rs999737 and rs10483813 (r 2=0.98) at 14q24.1 (RAD51L1), for up to 46 036 invasive breast cancer cases and 46 930 controls from 39 studies. Analyses by tumor characteristics focused on subjects reporting to be white women of European ancestry and were based on 25 458 cases, of which 87% had ER data. The SNP at 1p11.2 showed significantly stronger associations with ER-positive tumors [per-allele odds ratio (OR) for ER-positive tumors was 1.13, 95% CI =1.10-1.16 and, for ER-negative tumors, OR was 1.03, 95% CI =0.98-1.07, case-only P-heterogeneity =7.6 × 10 -5]. The association with ER-positive tumors was stronger for tumors of lower grade (case-only P=6.7 × 10 -3) and lobular histology (case-only P=0.01). SNPs at 14q24.1 were associated with risk for most tumor subtypes evaluated, including triple-negative breast cancers, which has not been described previously. Our results underscore the need for large pooling efforts with tumor pathology data to help refine risk estimates for SNP associations with susceptibility to different subtypes of breast cancer. Published by Oxford University Press 2011.
UR - http://www.scopus.com/inward/record.url?scp=81255209196&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddr368
DO - 10.1093/hmg/ddr368
M3 - Article
C2 - 21852249
AN - SCOPUS:81255209196
SN - 0964-6906
VL - 20
SP - 4693
EP - 4706
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 23
M1 - ddr368
ER -