Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer.


Milne, RL; Goode, EL; García-Closas, M; Couch, FJ; Severi, G; Hein, R; Fredericksen, Z; Malats, N; Zamora, MP; Arias Pérez, JI; Benítez, J; Dörk, T; Schürmann, P; Karstens, JH; Hillemanns, P; Cox, A; Brock, IW; Elliot, G; Cross, SS; Seal, S; Turnbull, C; Renwick, A; Rahman, N; Shen, CY; Yu, JC; Huang, CS; Hou, MF; Nordestgaard, BG; Bojesen, SE; Lanng, C; Grenaker Alnæs, G; Kristensen, V; Børrensen-Dale, AL; Hopper, JL; Dite, GS; Apicella, C; Southey, MC; Lambrechts, D; Yesilyurt, BT; Floris, G; Leunen, K; Sangrajrang, S; Gaborieau, V; Brennan, P; McKay, J; Chang-Claude, J; Wang-Gohrke, S; Radice, P; Peterlongo, P; Manoukian, S; Barile, M; Giles, GG; Baglietto, L; John, EM; Miron, A; Chanock, SJ; Lissowska, J; Sherman, ME; Figueroa, JD; Bogdanova, NV; Antonenkova, NN; Zalutsky, IV; Rogov, YI; Fasching, PA; Bayer, CM; Ekici, AB; Beckmann, MW; Brenner, H; Müller, H; Arndt, V; Stegmaier, C; Andrulis, IL; Knight, JA; Glendon, G; Mulligan, AM; Mannermaa, A; Kataja, V; Kosma, VM; Hartikainen, JM; Meindl, A; Heil, J; Bartram, CR; Schmutzler, RK; Thomas, GD; Hoover, RN; Fletcher, O; Gibson, LJ; dos Santos Silva, I; Peto, J; Nickels, S; Flesch-Janys, D; Anton-Culver, H; Ziogas, A; Sawyer, E; Tomlinson, I; Kerin, M; Miller, N; Schmidt, MK; Broeks, A; Van 't Veer, LJ; Tollenaar, RA; Pharoah, PD; Dunning, AM; Pooley, KA; Marme, F; Schneeweiss, A; Sohn, C; Burwinkel, B; Jakubowska, A; Lubinski, J; Jaworska, K; Durda, K; Kang, D; Yoo, KY; Noh, DY; Ahn, SH; Hunter, DJ; Hankinson, SE; Kraft, P; Lindstrom, S; Chen, X; Beesley, J; Hamann, U; Harth, V; Justenhoven, C; GENICA Network, ; Winqvist, R; Pylkäs, K; Jukkola-Vuorinen, A; Grip, M; Hooning, M; Hollestelle, A; Oldenburg, RA; Tilanus-Linthorst, M; Khusnutdinova, E; Bermisheva, M; Prokofieva, D; Farahtdinova, A; Olson, JE; Wang, X; Humphreys, MK; Wang, Q; Chenevix-Trench, G; kConFab Investigators, ; AOCS Group, ; Easton, DF; (2011) Confirmation of 5p12 As a Susceptibility Locus for Progesterone-Receptor-Positive, Lower Grade Breast Cancer. Cancer epidemiology, biomarkers & prevention, 20 (10). pp. 2222-31. ISSN 1055-9965 DOI: https://doi.org/10.1158/1055-9965.EPI-11-0569

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Abstract

BACKGROUND: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium.<br/> METHODS: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression.<br/> RESULTS: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10(-18)) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)-positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10(-18) vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P(heterogeneity) = 2 × 10(-7)); heterogeneity by ER status was not observed (P = 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; P(trend) = 5 × 10(-7)].<br/> CONCLUSION: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer.<br/> IMPACT: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants.<br/>

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Faculty of Epidemiology and Population Health > Dept of Medical Statistics
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 21795498
Web of Science ID: 295717900028
URI: http://researchonline.lshtm.ac.uk/id/eprint/40

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