Peer-Reviewed Journal Details
Mandatory Fields
Warren, H,Dudbridge, F,Fletcher, O,Orr, N,Johnson, N,Hopper, JL,Apicella, C,Southey, MC,Mahmoodi, M,Schmidt, MK,Broeks, A,Cornelissen, S,Braaf, LM,Muir, KR,Lophatananon, A,Chaiwerawattana, A,Wiangnon, S,Fasching, PA,Beckmann, MW,Ekici, AB,Schulz-Wendtland, R,Sawyer, EJ,Tomlinson, I,Kerin, M,Burwinkel, B,Marme, F,Schneeweiss, A,Sohn, C,Guenel, P,Truong, T,Laurent-Puig, P,Mulot, C,Bojesen, SE,Nielsen, SF,Flyger, H,Nordestgaard, BG,Milne, RL,Benitez, J,Arias-Perez, JI,Zamora, MP,Anton-Culver, H,Ziogas, A,Bernstein, L,Dur, CC,Brenner, H,Muller, H,Arndt, V,Langheinz, A,Meindl, A,Golatta, M,Bartram, CR,Schmutzler, RK,Brauch, H,Justenhoven, C,Bruning, T,Chang-Claude, J,Wang-Gohrke, S,Eilber, U,Dork, T,Schurmann, P,Bremer, M,Hillemanns, P,Nevanlinna, H,Muranen, TA,Aittomaki, K,Blomqvist, C,Bogdan
2012
October
Cancer Epidemiology Biomarkers & Prevention
9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium
Published
Optional Fields
GENOME-WIDE ASSOCIATION CONFER SUSCEPTIBILITY COMMON VARIANTS GENETIC RISK IDENTIFIES 2 POPULATION MENARCHE ALLELES LINKAGE 5P12
21
1783
1791
Background: Our recent genome-wide association study identified a novel breast cancer susceptibility locus at 9q31.2 (rs865686).Methods: To further investigate the rs865686-breast cancer association, we conducted a replication study within the Breast Cancer Association Consortium, which comprises 37 case-control studies (48,394 cases, 50,836 controls).Results: This replication study provides additional strong evidence of an inverse association between rs865686 and breast cancer risk [study-adjusted per G-allele OR, 0.90; 95% confidence interval (CI), 0.88; 0.91, P = 2.01 x 10(-29)] among women of European ancestry. There were ethnic differences in the estimated minor (G)-allele frequency among controls [0.09, 0.30, and 0.38 among, respectively, Asians, Eastern Europeans, and other Europeans; P for heterogeneity (P-het) -1.3 x 10(-143)], but no evidence of ethnic differences in per allele OR (P-het = 0.43). rs865686 was associated with estrogen receptor-positive (ER+) disease (per G-allele OR, 0.89; 95% CI, 0.86-0.91; P = 3.13 x 10(-22)) but less strongly, if at all, with ER-negative (ER+) disease (OR, 0.98; 95% CI, 0.941.02; P = 0.26; P-het = 1.16 x 10(-6)), with no evidence of independent heterogeneity by progesterone receptor or HER2 status. The strength of the breast cancer association decreased with increasing age at diagnosis, with case-only analysis showing a trend in the number of copies of the Gallele with increasing age at diagnosis (P for linear trend = 0.0095), but only among women with ER+ tumors.Conclusions: This study is the first to show that rs865686 is a susceptibility marker for ER+ breast cancer. Impact: The findings further support the view that genetic susceptibility varies according to tumor subtype. Cancer Epidemiol Biomarkers Prev; 21(10); 1783-91. (c) 2012 AACR.
10.1158/1055-9965.EPI-12-0526
Grant Details
Publication Themes