Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes: Findings from the Breast Cancer Association Consortium
Journal
Human Molecular Genetics
Journal Volume
20
Journal Issue
16
Pages
3289-3303
Date Issued
2011
Author(s)
Broeks A.
Schmidt M.K.
Sherman M.E.
Couch F.J.
Hopper J.L.
Dite G.S.
Apicella C.
Smith L.D.
Hammet F.
Southey M.C.
Van't Veer L.J.
De Groot R.
Smit V.T.H.B.M.
Fasching P.A.
Beckmann M.W.
Jud S.
Ekici A.B.
Hartmann A.
Hein A.
Schulz-Wendtland R.
Burwinkel B.
Marme F.
Schneeweiss A.
Sinn H.-P.
Sohn C.
Tchatchou S.
Bojesen S.E.
Nordestgaard B.G.
Flyger H.
?rsted D.D.
Kaur-Knudsen D.
Milne R.L.
P?rez J.I.A.
Zamora P.
Rodr?guez P.M.
Ben?tez J.
Brauch H.
Justenhoven C.
Ko Y.-D.
Network T.G.
Hamann U.
Fischer H.-P.
Br?ning T.
Pesch B.
Chang-Claude J.
Wang-Gohrke S.
Bremer M.
Karstens J.H.
Hillemanns P.
D?rk T.
Nevanlinna H.A.
Heikkinen T.
Heikkil? P.
Blomqvist C.
Aittom?ki K.
Aaltonen K.
Lindblom A.
Margolin S.
Mannermaa A.
Kosma V.-M.
Kauppinen J.M.
Kataja V.
Auvinen P.
Eskelinen M.
Soini Y.
Chenevix-Trench G.
Spurdle A.B.
Beesley J.
Chen X.
Holland H.
Lambrechts D.
Claes B.
Vandorpe T.
Neven P.
Wildiers H.
Flesch-Janys D.
Hein R.
L?ning T.
Kosel M.
Fredericksen Z.S.
Wang X.
Giles G.G.
Baglietto L.
Severi G.
McLean C.
Haiman C.A.
Henderson B.E.
Le Marchand L.
Kolonel L.N.
Aln?s G.G.
Kristensen V.
B?rresen-Dale A.-L.
Hunter D.J.
Hankinson S.E.
Andrulis I.L.
Mulligan A.M.
O'Malley F.P.
Devilee P.
Huijts P.E.A.
Tollenaar R.A.E.M.
Van Asperen C.J.
Seynaeve C.S.
Chanock S.J.
Lissowska J.
Brinton L.
Peplonska B.
Figueroa J.
Yang X.R.
Hooning M.J.
Hollestelle A.
Oldenburg R.A.
Jager A.
Kriege M.
Ozturk B.
Van Leenders G.J.L.H.
Hall P.
Czene K.
Humphreys K.
Liu J.
Cox A.
Connley D.
Cramp H.E.
Cross S.S.
Balasubramanian S.P.
Reed M.W.R.
Dunning A.M.
Easton D.F.
Humphreys M.K.
Caldas C.
Blows F.
Driver K.
Provenzano E.
Lubinski J.
Jakubowska A.
Huzarski T.
Byrski T.
Cybulski C.
Gorski B.
Gronwald J.
Brennan P.
Sangrajrang S.
Gaborieau V.
Shen C.-Y.
Hsiung C.-N.
Yu J.-C.
Chen S.-T.
Hsu G.-C.
Hou M.-F.
Anton-Culver H.
Ziogas A.
Pharoah P.D.P.
Garcia-Closas M.
kConFab51, AOCS50,51
Abstract
Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations with ER1 than ER2 tumors for six of the eight loci identified in GWAS: rs2981582 (10q26) (P-heterogeneity = 6.1 × 10-18), rs3803662 (16q12) (P = 3.7 × 10-5), rs13281615 (8q24) (P = 0.002), rs13387042 (2q35) (P = 0.006), rs4973768 (3p24) (P = 0.003) and rs6504950 (17q23) (P = 0.002). The two candidate loci, CASP8 (rs1045485, rs17468277) and TGFB1 (rs1982073), were most strongly related with the risk of PR negative tumors (P = 5.1 × 10-6 and P = 4.1 × 10-4, respectively), as previously suggested. Four of the eight loci identified in GWAS were associated with triple negative tumors (P ? 0.016): rs3803662 (16q12), rs889312 (5q11), rs3817198 (11p15) and rs13387042 (2q35); however, only two of them (16q12 and 2q35) were associated with tumors with the core basal phenotype (P ? 0.002). These analyses are consistent with different biological origins of breast cancers, and indicate that tumor stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment. ? The Author 2011. Published by Oxford University Press. All rights reserved.
SDGs
Other Subjects
epidermal growth factor receptor 2; estrogen receptor; progesterone; vasculotropin receptor; epidermal growth factor receptor 2; estrogen receptor; HER2 protein, human; progesterone receptor; tumor marker; Article; Asian; breast cancer; cancer risk; cancer susceptibility; clinical article; clinical feature; disease association; female; genotype; human; human cell; penetrance; phenotype; priority journal; protein expression; risk factor; single nucleotide polymorphism; article; breast tumor; Caucasian; classification; gene locus; genetic predisposition; genetics; metabolism; penetrance; risk; Asian Continental Ancestry Group; Breast Neoplasms; European Continental Ancestry Group; Female; Genetic Loci; Genetic Predisposition to Disease; Humans; Odds Ratio; Penetrance; Receptor, erbB-2; Receptors, Estrogen; Receptors, Progesterone; Risk Factors; Tumor Markers, Biological
Publisher
Oxford University Press
Type
journal article