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Author: Hopper, John × Author: Milne, Roger × End date: 2012 × Start date: 2012 ×

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    11q13 is a susceptibility locus for hormone receptor positive breast cancer
    Lambrechts, D ; Truong, T ; Justenhoven, C ; Humphreys, MK ; Wang, J ; Hopper, JL ; Dite, GS ; Apicella, C ; Southey, MC ; Schmidt, MK ; Broeks, A ; Cornelissen, S ; van Hien, R ; Sawyer, E ; Tomlinson, I ; Kerin, M ; Miller, N ; Milne, RL ; Pilar Zamora, M ; Arias Perez, JI ; Benitez, J ; Hamann, U ; Ko, Y-D ; Bruening, T ; Chang-Claude, J ; Eilber, U ; Hein, R ; Nickels, S ; Flesch-Janys, D ; Wang-Gohrke, S ; John, EM ; Miron, A ; Winqvist, R ; Pylkas, K ; Jukkola-Vuorinen, A ; Grip, M ; Chenevix-Trench, G ; Beesley, J ; Chen, X ; Menegaux, F ; Cordina-Duverger, E ; Shen, C-Y ; Yu, J-C ; Wu, P-E ; Hou, M-F ; Andrulis, IL ; Selander, T ; Glendon, G ; Mulligan, AM ; Anton-Culver, H ; Ziogas, A ; Muir, KR ; Lophatananon, A ; Rattanamongkongul, S ; Puttawibul, P ; Jones, M ; Orr, N ; Ashworth, A ; Swerdlow, A ; Severi, G ; Baglietto, L ; Giles, G ; Southey, M ; Marme, F ; Schneeweiss, A ; Sohn, C ; Burwinkel, B ; Yesilyurt, BT ; Neven, P ; Paridaens, R ; Wildiers, H ; Brenner, H ; Mueller, H ; Arndt, V ; Stegmaier, C ; Meindl, A ; Schott, S ; Bartram, CR ; Schmutzler, RK ; Cox, A ; Brock, IW ; Elliott, G ; Cross, SS ; Fasching, PA ; Schulz-Wendtland, R ; Ekici, AB ; Beckmann, MW ; Fletcher, O ; Johnson, N ; Silva, IDS ; Peto, J ; Nevanlinna, H ; Muranen, TA ; Aittomaki, K ; Blomqvist, C ; Doerk, T ; Schuermann, P ; Bremer, M ; Hillemanns, P ; Bogdanova, NV ; Antonenkova, NN ; Rogov, YI ; Karstens, JH ; Khusnutdinova, E ; Bermisheva, M ; Prokofieva, D ; Gancev, S ; Jakubowska, A ; Lubinski, J ; Jaworska, K ; Durda, K ; Nordestgaard, BG ; Bojesen, SE ; Lanng, C ; Mannermaa, A ; Kataja, V ; Kosma, V-M ; Hartikainen, JM ; Radice, P ; Peterlongo, P ; Manoukian, S ; Bernard, L ; Couch, FJ ; Olson, JE ; Wang, X ; Fredericksen, Z ; Alnaes, GG ; Kristensen, V ; Borresen-Dale, A-L ; Devilee, P ; Tollenaar, RAEM ; Seynaeve, CM ; Hooning, MJ ; Garcia-Closas, M ; Chanock, SJ ; Lissowska, J ; Sherman, ME ; Hall, P ; Liu, J ; Czene, K ; Kang, D ; Yoo, K-Y ; Noh, D-Y ; Lindblom, A ; Margolin, S ; Dunning, AM ; Pharoah, PDP ; Easton, DF ; Guenel, P ; Brauch, H (WILEY, 2012-07)
    A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P ≤ 3 × 10(-9) ) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 × 10(-39) ). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype.
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    9q31.2-rs865686 as a Susceptibility Locus for Estrogen Receptor-Positive Breast Cancer: Evidence from the Breast Cancer Association Consortium
    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 ; Therese, T ; Laurent-Puig, P ; Mulot, C ; Bojesen, SE ; Nielsen, SF ; Flyger, H ; Nordestgaard, BG ; Milne, RL ; Benitez, J ; Arias-Perez, J-I ; Pilar Zamora, M ; Anton-Culver, H ; Ziogas, A ; Bernstein, L ; Dur, CC ; Brenner, H ; Mueller, H ; Arndt, V ; Langheinz, A ; Meindl, A ; Golatta, M ; Bartram, CR ; Schmutzler, RK ; Brauch, H ; Justenhoven, C ; Bruening, T ; Chang-Claude, J ; Wang-Gohrke, S ; Eilber, U ; Doerk, T ; Schuermann, P ; Bremer, M ; Hillemanns, P ; Nevanlinna, H ; Muranen, TA ; Aittomaki, K ; Blomqvist, C ; Bogdanova, N ; Antonenkova, N ; Rogov, Y ; Bermisheva, M ; Prokofyeva, D ; Zinnatullina, G ; Khusnutdinova, E ; Lindblom, A ; Margolin, S ; Mannermaa, A ; Kosma, V-M ; Hartikainen, JM ; Kataja, V ; Chenevix-Trench, G ; Beesley, J ; Chen, X ; Lambrechts, D ; Smeets, A ; Paridaens, R ; Weltens, C ; Flesch-Janys, D ; Buck, K ; Behrens, S ; Peterlongo, P ; Bernard, L ; Manoukian, S ; Radice, P ; Couch, FJ ; Vachon, C ; Wang, X ; Olson, J ; Giles, G ; Baglietto, L ; McLean, CA ; Severi, G ; John, EM ; Miron, A ; Winqvist, R ; Pylkas, K ; Jukkola-Vuorinen, A ; Grip, M ; Andrulis, IL ; Knight, JA ; Mulligan, AM ; Weerasooriya, N ; Devilee, P ; Tollenaar, RAEM ; Martens, JWM ; Seynaeve, CM ; Hooning, MJ ; Hollestelle, A ; Jager, A ; Tilanus-Linthorst, MMA ; Hall, P ; Czene, K ; Liu, J ; Li, J ; Cox, A ; Cross, SS ; Brock, IW ; Reed, MWR ; Pharoah, P ; Blows, FM ; Dunning, AM ; Ghous-saini, M ; Ashworth, A ; Swerdlow, A ; Jones, M ; Schoemaker, M ; Easton, DF ; Humphreys, M ; Wang, Q ; Peto, J ; dos-Santos-Silva, I (AMER ASSOC CANCER RESEARCH, 2012-10)
    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.