Title: 9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the Breast Cancer Association Consortium
Authors: Warren, H ×
Dudbridge, F
Fletcher, O
Orr, N
Johnson, N
Hopper, J L
Apicella, C
Southey, M C
Mahmoodi, M
Schmidt, M K
Broeks, A
Severi, G
John, E M
Miron, A
Winqvist, R
Pylkäs, K
Jukkola-Vuorinen, A
Grip, M
Andrulis, I L
Knight, J A
Mulligan, A M
Cornelissen, S
Weerasooriya, N
Devilee, P
Tollenaar, R A
Martens, J W
Seynaeve, C M
Hooning, M J
Hollestelle, A
Jager, A
Tilanus-Linthorst, M M
Hall, P
Braaf, L M
Czene, K
Liu, J
Li, J
Cox, A
Cross, S S
Brock, I W
Reed, M W
Pharoah, P
Blows, F M
Dunning, A M
Muir, K R
Ghoussaini, M
Ashworth, A
Swerdlow, A
Jones, M
Schoemaker, M
Easton, D F
Humphreys, M
Wang, Q
Peto, J
Dos-Santos-Silva, I
Lophatananon, A
Chaiwerawattana, A
Wiangnon, S
Fasching, P A
Beckmann, M W
Ekici, A B
Schulz-Wendtland, R
Sawyer, E J
Tomlinson, I
Kerin, M
Burwinkel, B
Marme, F
Schneeweiss, A
Sohn, C
Guénel, P
Truong, T
Laurent-Puig, P
Mulot, C
Bojesen, S E
Nielsen, S F
Flyger, H
Nordestgaard, B G
Milne, R L
Benítez, J
Arias-Pérez, J I
Zamora, M P
Anton-Culver, H
Ziogas, A
Bernstein, L
Dur, C C
Brenner, H
Müller, H
Arndt, V
Langheinz, A
Meindl, A
Golatta, M
Bartram, C R
Schmutzler, R K
Brauch, H
Justenhoven, C
Brüning, T
Chang-Claude, J
Wang-Gohrke, S
Eilber, U
Dörk, T
Schürmann, P
Bremer, M
Hillemanns, P
Nevanlinna, H
Muranen, T A
Aittomäki, K
Blomqvist, C
Bogdanova, N
Antonenkova, N
Rogov, Y
Bermisheva, M
Prokofyeva, D
Zinnatullina, G
Khusnutdivona, E
Lindblom, A
Margolin, S
Mannermaa, A
Kosma, V M
Hartikainen, J M
Kataja, V
Chenevix-Trench, G
Beesley, J
Chen, X
Lambrechts, Diether
Smeets, Ann
Paridaens, Robert
Weltens, Caroline
Flesch-Janys, D
Buck, K
Behrens, S
Peterlongo, P
Bernard, L
Manoukian, S
Radice, P
Couch, F J
Vachon, C
Wang, X
Olson, J
Giles, G
Baglietto, L
McLean, C A #
Issue Date: Oct-2012
Publisher: American Association for Cancer Research
Series Title: Cancer Epidemiology, Biomarkers & Prevention vol:21 issue:10 pages:1783-1791
Abstract: 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 × 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 × 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 × 10(-22)) but less strongly, if at all, with ER-negative (ER(-)) disease (OR, 0.98; 95% CI, 0.94-1.02; P = 0.26; P(het) = 1.16 × 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 G allele 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.
ISSN: 1055-9965
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Experimental Oncology
Laboratory of Translational Genetics (Vesalius Research Center) (+)
Surgical Oncology
Laboratory of Experimental Radiotherapy
× corresponding author
# (joint) last author

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