Sir Peter MacCallum Department of Oncology - Research Publications

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    Common variants in breast cancer risk loci predispose to distinct tumor subtypes
    Ahearn, TU ; Zhang, H ; Michailidou, K ; Milne, RL ; Bolla, MK ; Dennis, J ; Dunning, AM ; Lush, M ; Wang, Q ; Andrulis, IL ; Anton-Culver, H ; Arndt, V ; Aronson, KJ ; Auer, PL ; Augustinsson, A ; Baten, A ; Becher, H ; Behrens, S ; Benitez, J ; Bermisheva, M ; Blomqvist, C ; Bojesen, SE ; Bonanni, B ; Borresen-Dale, A-L ; Brauch, H ; Brenner, H ; Brooks-Wilson, A ; Bruening, T ; Burwinkel, B ; Buys, SS ; Canzian, F ; Castelao, JE ; Chang-Claude, J ; Chanock, SJ ; Chenevix-Trench, G ; Clarke, CL ; Collee, JM ; Cox, A ; Cross, SS ; Czene, K ; Daly, MB ; Devilee, P ; Dork, T ; Dwek, M ; Eccles, DM ; Evans, DG ; Fasching, PA ; Figueroa, J ; Floris, G ; Gago-Dominguez, M ; Gapstur, SM ; Garcia-Saenz, JA ; Gaudet, MM ; Giles, GG ; Goldberg, MS ; Gonzalez-Neira, A ; Alnaes, GIG ; Grip, M ; Guenel, P ; Haiman, CA ; Hall, P ; Hamann, U ; Harkness, EF ; Heemskerk-Gerritsen, BAM ; Holleczek, B ; Hollestelle, A ; Hooning, MJ ; Hoover, RN ; Hopper, JL ; Howell, A ; Jakimovska, M ; Jakubowska, A ; John, EM ; Jones, ME ; Jung, A ; Kaaks, R ; Kauppila, S ; Keeman, R ; Khusnutdinova, E ; Kitahara, CM ; Ko, Y-D ; Koutros, S ; Kristensen, VN ; Kruger, U ; Kubelka-Sabit, K ; Kurian, AW ; Kyriacou, K ; Lambrechts, D ; Lee, DG ; Lindblom, A ; Linet, M ; Lissowska, J ; Llaneza, A ; Lo, W-Y ; MacInnis, RJ ; Mannermaa, A ; Manoochehri, M ; Margolin, S ; Martinez, ME ; McLean, C ; Meindl, A ; Menon, U ; Nevanlinna, H ; Newman, WG ; Nodora, J ; Offit, K ; Olsson, H ; Orr, N ; Park-Simon, T-W ; Patel, A ; Peto, J ; Pita, G ; Plaseska-Karanfilska, D ; Prentice, R ; Punie, K ; Pylkas, K ; Radice, P ; Rennert, G ; Romero, A ; Ruediger, T ; Saloustros, E ; Sampson, S ; Sandler, DP ; Sawyer, EJ ; Schmutzler, RK ; Schoemaker, MJ ; Schottker, B ; Sherman, ME ; Shu, X-O ; Smichkoska, S ; Southey, MC ; Spinelli, JJ ; Swerdlow, AJ ; Tamimi, RM ; Tapper, WJ ; Taylor, JA ; Teras, LR ; Terry, MB ; Torres, D ; Troester, MA ; Vachon, CM ; van Deurzen, CHM ; van Veen, EM ; Wagner, P ; Weinberg, CR ; Wendt, C ; Wesseling, J ; Winqvist, R ; Wolk, A ; Yang, XR ; Zheng, W ; Couch, FJ ; Simard, J ; Kraft, P ; Easton, DF ; Pharoah, PDP ; Schmidt, MK ; Garcia-Closas, M ; Chatterjee, N (BMC, 2022-01-04)
    BACKGROUND: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. METHODS: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. RESULTS: Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions. CONCLUSION: This report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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    Rare germline copy number variants (CNVs) and breast cancer risk
    Dennis, J ; Tyrer, JP ; Walker, LC ; Michailidou, K ; Dorling, L ; Bolla, MK ; Wang, Q ; Ahearn, TU ; Andrulis, IL ; Anton-Culver, H ; Antonenkova, NN ; Arndt, V ; Aronson, KJ ; Freeman, LEB ; Beckmann, MW ; Behrens, S ; Benitez, J ; Bermisheva, M ; Bogdanova, N ; Bojesen, SE ; Brenner, H ; Castelao, JE ; Chang-Claude, J ; Chenevix-Trench, G ; Clarke, CL ; Collee, JM ; Couch, FJ ; Cox, A ; Cross, SS ; Czene, K ; Devilee, P ; Dork, T ; Dossus, L ; Eliassen, AH ; Eriksson, M ; Evans, DG ; Fasching, PA ; Figueroa, J ; Fletcher, O ; Flyger, H ; Fritschi, L ; Gabrielson, M ; Gago-Dominguez, M ; Garcia-Closas, M ; Giles, GG ; Gonzalez-Neira, A ; Guenel, P ; Hahnen, E ; Haiman, CA ; Hall, P ; Hollestelle, A ; Hoppe, R ; Hopper, JL ; Howell, A ; Jager, A ; Jakubowska, A ; John, EM ; Johnson, N ; Jones, ME ; Jung, A ; Kaaks, R ; Keeman, R ; Khusnutdinova, E ; Kitahara, CM ; Ko, Y-D ; Kosma, V-M ; Koutros, S ; Kraft, P ; Kristensen, VN ; Kubelka-Sabit, K ; Kurian, AW ; Lacey, J ; Lambrechts, D ; Larson, NL ; Linet, M ; Ogrodniczak, A ; Mannermaa, A ; Manoukian, S ; Margolin, S ; Mavroudis, D ; Milne, RL ; Muranen, TA ; Murphy, RA ; Nevanlinna, H ; Olson, JE ; Olsson, H ; Park-Simon, T-W ; Perou, CM ; Peterlongo, P ; Plaseska-Karanfilska, D ; Pylkas, K ; Rennert, G ; Saloustros, E ; Sandler, DP ; Sawyer, EJ ; Schmidt, MK ; Schmutzler, RK ; Shibli, R ; Smeets, A ; Soucy, P ; Southey, MC ; Swerdlow, AJ ; Tamimi, RM ; Taylor, JA ; Teras, LR ; Terry, MB ; Tomlinson, I ; Troester, MA ; Truong, T ; Vachon, CM ; Wendt, C ; Winqvist, R ; Wolk, A ; Yang, XR ; Zheng, W ; Ziogas, A ; Simard, J ; Dunning, AM ; Pharoah, PDP ; Easton, DF (NATURE PORTFOLIO, 2022-01-18)
    Germline copy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data. Gene burden tests detected the strongest association for deletions in BRCA1 (P = 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P = 0.0008), ATM (P = 0.002) and BRCA2 (P = 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci. To the best of our knowledge, this is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.
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    Mendelian randomisation study of smoking exposure in relation to breast cancer risk
    Park, HA ; Neumeyer, S ; Michailidou, K ; Bolla, MK ; Wang, Q ; Dennis, J ; Ahearn, TU ; Andrulis, IL ; Anton-Culver, H ; Antonenkova, NN ; Arndt, V ; Aronson, KJ ; Augustinsson, A ; Baten, A ; Freeman, LEB ; Becher, H ; Beckmann, MW ; Behrens, S ; Benitez, J ; Bermisheva, M ; Bogdanova, N ; Bojesen, SE ; Brauch, H ; Brenner, H ; Brucker, SY ; Burwinkel, B ; Campa, D ; Canzian, F ; Castelao, JE ; Chanock, SJ ; Chenevix-Trench, G ; Clarke, CL ; Conroy, DM ; Couch, FJ ; Cox, A ; Cross, SS ; Czene, K ; Daly, MB ; Devilee, P ; Dork, T ; Dos-Santos-Silva, I ; Dwek, M ; Eccles, DM ; Eliassen, AH ; Engel, C ; Eriksson, M ; Evans, DG ; Fasching, PA ; Flyger, H ; Fritschi, L ; Garcia-Closas, M ; Garcia-Saenz, JA ; Gaudet, MM ; Giles, GG ; Glendon, G ; Goldberg, MS ; Goldgar, DE ; Gonzalez-Neira, A ; Grip, M ; Guenel, P ; Hahnen, E ; Haiman, CA ; Hakansson, N ; Hall, P ; Hamann, U ; Han, S ; Harkness, EF ; Hart, SN ; He, W ; Heemskerk-Gerritsen, BAM ; Hopper, JL ; Hunter, DJ ; Jager, A ; Jakubowska, A ; John, EM ; Jung, A ; Kaaks, R ; Kapoor, PM ; Keeman, R ; Khusnutdinova, E ; Kitahara, CM ; Koppert, LB ; Koutros, S ; Kristensen, VN ; Kurian, AW ; Lacey, J ; Lambrechts, D ; LeMarchand, L ; Lo, W-Y ; Mannermaa, A ; Manoochehri, M ; Margolin, S ; ElenaMartinez, M ; Mavroudis, D ; Meindl, A ; Menon, U ; Milne, RL ; Muranen, TA ; Nevanlinna, H ; Newman, WG ; Nordestgaard, BG ; Offit, K ; Olshan, AF ; Olsson, H ; Park-Simon, T-W ; Peterlongo, P ; Peto, J ; Plaseska-Karanfilska, D ; Presneau, N ; Radice, P ; Rennert, G ; Rennert, HS ; Romero, A ; Saloustros, E ; Sawyer, EJ ; Schmidt, MK ; Schmutzler, RK ; Schoemaker, MJ ; Schwentner, L ; Scott, C ; Shah, M ; Shu, X-O ; Simard, J ; Smeets, A ; Southey, MC ; Spinelli, JJ ; Stevens, V ; Swerdlow, AJ ; Tamimi, RM ; Tapper, WJ ; Taylor, JA ; Terry, MB ; Tomlinson, I ; Troester, MA ; Truong, T ; Vachon, CM ; van Veen, EM ; Vijai, J ; Wang, S ; Wendt, C ; Winqvist, R ; Wolk, A ; Ziogas, A ; Dunning, AM ; Pharoah, PDP ; Easton, DF ; Zheng, W ; Kraft, P ; Chang-Claude, J (SPRINGERNATURE, 2021-08-02)
    BACKGROUND: Despite a modest association between tobacco smoking and breast cancer risk reported by recent epidemiological studies, it is still equivocal whether smoking is causally related to breast cancer risk. METHODS: We applied Mendelian randomisation (MR) to evaluate a potential causal effect of cigarette smoking on breast cancer risk. Both individual-level data as well as summary statistics for 164 single-nucleotide polymorphisms (SNPs) reported in genome-wide association studies of lifetime smoking index (LSI) or cigarette per day (CPD) were used to obtain MR effect estimates. Data from 108,420 invasive breast cancer cases and 87,681 controls were used for the LSI analysis and for the CPD analysis conducted among ever-smokers from 26,147 cancer cases and 26,072 controls. Sensitivity analyses were conducted to address pleiotropy. RESULTS: Genetically predicted LSI was associated with increased breast cancer risk (OR 1.18 per SD, 95% CI: 1.07-1.30, P = 0.11 × 10-2), but there was no evidence of association for genetically predicted CPD (OR 1.02, 95% CI: 0.78-1.19, P = 0.85). The sensitivity analyses yielded similar results and showed no strong evidence of pleiotropic effect. CONCLUSION: Our MR study provides supportive evidence for a potential causal association with breast cancer risk for lifetime smoking exposure but not cigarettes per day among smokers.
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    CYP3A7*1C allele: linking premenopausal oestrone and progesterone levels with risk of hormone receptor-positive breast cancers
    Johnson, N ; Maguire, S ; Morra, A ; Kapoor, PM ; Tomczyk, K ; Jones, ME ; Schoemaker, MJ ; Gilham, C ; Bolla, MK ; Wang, Q ; Dennis, J ; Ahearn, TU ; Andrulis, IL ; Anton-Culver, H ; Antonenkova, NN ; Arndt, V ; Aronson, KJ ; Augustinsson, A ; Baynes, C ; Freeman, LEB ; Beckmann, MW ; Benitez, J ; Bermisheva, M ; Blomqvist, C ; Boeckx, B ; Bogdanova, NV ; Bojesen, SE ; Brauch, H ; Brenner, H ; Burwinkel, B ; Campa, D ; Canzian, F ; Castelao, JE ; Chanock, SJ ; Chenevix-Trench, G ; Clarke, CL ; Conroy, DM ; Couch, FJ ; Cox, A ; Cross, SS ; Czene, K ; Doerk, T ; Eliassen, AH ; Engel, C ; Evans, DG ; Fasching, PA ; Figueroa, J ; Floris, G ; Flyger, H ; Gago-Dominguez, M ; Gapstur, SM ; Garcia-Closas, M ; Gaudet, MM ; Giles, GG ; Goldberg, MS ; Gonzalez-Neira, A ; Guenel, P ; Hahnen, E ; Haiman, CA ; Hakansson, N ; Hall, P ; Hamann, U ; Harrington, PA ; Hart, SN ; Hooning, MJ ; Hopper, JL ; Howell, A ; Hunter, DJ ; Jager, A ; Jakubowska, A ; John, EM ; Kaaks, R ; Keeman, R ; Khusnutdinova, E ; Kitahara, CM ; Kosma, V-M ; Koutros, S ; Kraft, P ; Kristensen, VN ; Kurian, AW ; Lambrechts, D ; Le Marchand, L ; Linet, M ; Lubinski, J ; Mannermaa, A ; Manoukian, S ; Margolin, S ; Martens, JWM ; Mavroudis, D ; Mayes, R ; Meindl, A ; Milne, RL ; Neuhausen, SL ; Nevanlinna, H ; Newman, WG ; Nielsen, SF ; Nordestgaard, BG ; Obi, N ; Olshan, AF ; Olson, JE ; Olsson, H ; Orban, E ; Park-Simon, T-W ; Peterlongo, P ; Plaseska-Karanfilska, D ; Pylkas, K ; Rennert, G ; Rennert, HS ; Ruddy, KJ ; Saloustros, E ; Sandler, DP ; Sawyer, EJ ; Schmutzler, RK ; Scott, C ; Shu, X-O ; Simard, J ; Smichkoska, S ; Sohn, C ; Southey, MC ; Spinelli, JJ ; Stone, J ; Tamimi, RM ; Taylor, JA ; Tollenaar, RAEM ; Tomlinson, I ; Troester, MA ; Truong, T ; Vachon, CM ; van Veen, EM ; Wang, SS ; Weinberg, CR ; Wendt, C ; Wildiers, H ; Winqvist, R ; Wolk, A ; Zheng, W ; Ziogas, A ; Dunning, AM ; Pharoah, PDP ; Easton, DF ; Howie, AF ; Peto, J ; dos-Santos-Silva, I ; Swerdlow, AJ ; Chang-Claude, J ; Schmidt, MK ; Orr, N ; Fletcher, O (SPRINGERNATURE, 2021-01-26)
    BACKGROUND: Epidemiological studies provide strong evidence for a role of endogenous sex hormones in the aetiology of breast cancer. The aim of this analysis was to identify genetic variants that are associated with urinary sex-hormone levels and breast cancer risk. METHODS: We carried out a genome-wide association study of urinary oestrone-3-glucuronide and pregnanediol-3-glucuronide levels in 560 premenopausal women, with additional analysis of progesterone levels in 298 premenopausal women. To test for the association with breast cancer risk, we carried out follow-up genotyping in 90,916 cases and 89,893 controls from the Breast Cancer Association Consortium. All women were of European ancestry. RESULTS: For pregnanediol-3-glucuronide, there were no genome-wide significant associations; for oestrone-3-glucuronide, we identified a single peak mapping to the CYP3A locus, annotated by rs45446698. The minor rs45446698-C allele was associated with lower oestrone-3-glucuronide (-49.2%, 95% CI -56.1% to -41.1%, P = 3.1 × 10-18); in follow-up analyses, rs45446698-C was also associated with lower progesterone (-26.7%, 95% CI -39.4% to -11.6%, P = 0.001) and reduced risk of oestrogen and progesterone receptor-positive breast cancer (OR = 0.86, 95% CI 0.82-0.91, P = 6.9 × 10-8). CONCLUSIONS: The CYP3A7*1C allele is associated with reduced risk of hormone receptor-positive breast cancer possibly mediated via an effect on the metabolism of endogenous sex hormones in premenopausal women.
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    Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes
    Fachal, L ; Aschard, H ; Beesley, J ; Barnes, DR ; Allen, J ; Kar, S ; Pooley, KA ; Dennis, J ; Michailidou, K ; Turman, C ; Soucy, P ; Lemacon, A ; Lush, M ; Tyrer, JP ; Ghoussaini, M ; Marjaneh, MM ; Jiang, X ; Agata, S ; Aittomaki, K ; Rosario Alonso, M ; Andrulis, IL ; Anton-Culver, H ; Antonenkova, NN ; Arason, A ; Arndt, V ; Aronson, KJ ; Arun, BK ; Auber, B ; Auer, PL ; Azzollini, J ; Balmana, J ; Barkardottir, RB ; Barrowdale, D ; Beeghly-Fadiel, A ; Benitez, J ; Bermisheva, M ; Bialkowska, K ; Blanco, AM ; Blomqvist, C ; Blot, W ; Bogdanova, N ; Bojesen, SE ; Bolla, MK ; Bonanni, B ; Borg, A ; Bosse, K ; Brauch, H ; Brenner, H ; Briceno, I ; Brock, IW ; Brooks-Wilson, A ; Bruening, T ; Burwinkel, B ; Buys, SS ; Cai, Q ; Caldes, T ; Caligo, MA ; Camp, NJ ; Campbell, I ; Canzian, F ; Carroll, JS ; Carter, BD ; Castelao, JE ; Chiquette, J ; Christiansen, H ; Chung, WK ; Claes, KBM ; Clarke, CL ; Collee, JM ; Cornelissen, S ; Couch, FJ ; Cox, A ; Cross, SS ; Cybulski, C ; Czene, K ; Daly, MB ; de la Hoya, M ; Devilee, P ; Diez, O ; Ding, YC ; Dite, GS ; Domchek, SM ; Doerk, T ; dos-Santos-Silva, I ; Droit, A ; Dubois, S ; Dumont, M ; Duran, M ; Durcan, L ; Dwek, M ; Eccles, DM ; Engel, C ; Eriksson, M ; Evans, DG ; Fasching, PA ; Fletcher, O ; Floris, G ; Flyger, H ; Foretova, L ; Foulkes, WD ; Friedman, E ; Fritschi, L ; Frost, D ; Gabrielson, M ; Gago-Dominguez, M ; Gambino, G ; Ganz, PA ; Gapstur, SM ; Garber, J ; Garcia-Saenz, JA ; Gaudet, MM ; Georgoulias, V ; Giles, GG ; Glendon, G ; Godwin, AK ; Goldberg, MS ; Goldgar, DE ; Gonzalez-Neira, A ; Tibiletti, MG ; Greene, MH ; Grip, M ; Gronwald, J ; Grundy, A ; Guenel, P ; Hahnen, E ; Haiman, CA ; Hakansson, N ; Hall, P ; Hamann, U ; Harrington, PA ; Hartikainen, JM ; Hartman, M ; He, W ; Healey, CS ; Heemskerk-Gerritsen, BAM ; Heyworth, J ; Hillemanns, P ; Hogervorst, FBL ; Hollestelle, A ; Hooning, MJ ; Hopper, JL ; Howell, A ; Huang, G ; Hulick, PJ ; Imyanitov, EN ; Isaacs, C ; Iwasaki, M ; Jager, A ; Jakimovska, M ; Jakubowska, A ; James, PA ; Janavicius, R ; Jankowitz, RC ; John, EM ; Johnson, N ; Jones, ME ; Jukkola-Vuorinen, A ; Jung, A ; Kaaks, R ; Kang, D ; Kapoor, PM ; Karlan, BY ; Keeman, R ; Kerin, MJ ; Khusnutdinova, E ; Kiiski, J ; Kirk, J ; Kitahara, CM ; Ko, Y-D ; Konstantopoulou, I ; Kosma, V-M ; Koutros, S ; Kubelka-Sabit, K ; Kwong, A ; Kyriacou, K ; Laitman, Y ; Lambrechts, D ; Lee, E ; Leslie, G ; Lester, J ; Lesueur, F ; Lindblom, A ; Lo, W-Y ; Long, J ; Lophatananon, A ; Loud, JT ; Lubinski, J ; MacInnis, RJ ; Maishman, T ; Makalic, E ; Mannermaa, A ; Manoochehri, M ; Manoukian, S ; Margolin, S ; Martinez, ME ; Matsuo, K ; Maurer, T ; Mavroudis, D ; Mayes, R ; McGuffog, L ; McLean, C ; Mebirouk, N ; Meindl, A ; Miller, A ; Miller, N ; Montagna, M ; Moreno, F ; Muir, K ; Mulligan, AM ; Munoz-Garzon, VM ; Muranen, TA ; Narod, SA ; Nassir, R ; Nathanson, KL ; Neuhausen, SL ; Nevanlinna, H ; Neven, P ; Nielsen, FC ; Nikitina-Zake, L ; Norman, A ; Offit, K ; Olah, E ; Olopade, O ; Olsson, H ; Orr, N ; Osorio, A ; Pankratz, VS ; Papp, J ; Park, SK ; Park-Simon, T-W ; Parsons, MT ; Paul, J ; Pedersen, IS ; Peissel, B ; Peshkin, B ; Peterlongo, P ; Peto, J ; Plaseska-Karanfilska, D ; Prajzendanc, K ; Prentice, R ; Presneau, N ; Prokofyeva, D ; Angel Pujana, M ; Pylkas, K ; Radice, P ; Ramus, SJ ; Rantala, J ; Rau-Murthy, R ; Rennert, G ; Risch, HA ; Robson, M ; Romero, A ; Rossing, M ; Saloustros, E ; Sanchez-Herrero, E ; Sandler, DP ; Santamarina, M ; Saunders, C ; Sawyer, EJ ; Scheuner, MT ; Schmidt, DF ; Schmutzler, RK ; Schneeweiss, A ; Schoemaker, MJ ; Schoettker, B ; Schuermann, P ; Scott, C ; Scott, RJ ; Senter, L ; Seynaeve, CM ; Shah, M ; Sharma, P ; Shen, C-Y ; Shu, X-O ; Singer, CF ; Slavin, TP ; Smichkoska, S ; Southey, MC ; Spinelli, JJ ; Spurdle, AB ; Stone, J ; Stoppa-Lyonnet, D ; Sutter, C ; Swerdlow, AJ ; Tamimi, RM ; Tan, YY ; Tapper, WJ ; Taylor, JA ; Teixeira, MR ; Tengstroem, M ; Teo, SH ; Terry, MB ; Teul, A ; Thomassen, M ; Thull, DL ; Tischkowitz, M ; Toland, AE ; Tollenaar, RAEM ; Tomlinson, I ; Torres, D ; Torres-Mejia, G ; Troester, MA ; Truong, T ; Tung, N ; Tzardi, M ; Ulmer, H-U ; Vachon, CM ; van Asperen, CJ ; van der Kolk, LE ; van Rensburg, EJ ; Vega, A ; Viel, A ; Vijai, J ; Vogel, MJ ; Wang, Q ; Wappenschmidt, B ; Weinberg, CR ; Weitzel, JN ; Wendt, C ; Wildiers, H ; Winqvist, R ; Wolk, A ; Wu, AH ; Yannoukakos, D ; Zhang, Y ; Zheng, W ; Hunter, D ; Pharoah, PDP ; Chang-Claude, J ; Garcia-Closas, M ; Schmidt, MK ; Milne, RL ; Kristensen, VN ; French, JD ; Edwards, SL ; Antoniou, AC ; Chenevix-Trench, G ; Simard, J ; Easton, DF ; Kraft, P ; Dunning, AM ; Mari, V ; Berthet, P ; Castera, L ; Vaur, D ; Lallaoui, H ; Bignon, Y-J ; Uhrhammer, N ; Bonadona, V ; Lasset, C ; Revillion, F ; Vennin, P ; Muller, D ; Gomes, DM ; Ingster, O ; Coupier, I ; Pujol, P ; Collonge-Rame, M-A ; Mortemousque, I ; Bera, O ; Rose, M ; Baurand, A ; Bertolone, G ; Faivre, L ; Dreyfus, H ; Leroux, D ; Venat-Bouvet, L ; Bezieau, S ; Delnatte, C ; Chiesa, J ; Gilbert-Dussardier, B ; Gesta, P ; Prieur, FP ; Bronner, M ; Sokolowska, J ; Coulet, F ; Boutry-Kryza, N ; Calender, A ; Giraud, S ; Leone, M ; Fert-Ferrer, S ; Jiao, Y ; Lesueur, FL ; Barouk-Simonet, E ; Bubien, V ; Longy, M ; Sevenet, N ; Gladieff, L ; Toulas, C ; Reimineras, A ; Sobol, H ; Bressac-de Paillerets, B ; Cabaret, O ; Caron, O ; Guillaud-Bataille, M ; Rouleau, E ; Belotti, M ; Buecher, B ; Caputo, S ; Colas, C ; De Pauw, A ; Fourme, E ; Gauthier-Villars, M ; Golmard, L ; Moncoutier, V ; Saule, C ; Donaldson, A ; Murray, A ; Brady, A ; Brewer, C ; Pottinger, C ; Miller, C ; Gallagher, D ; Gregory, H ; Cook, J ; Eason, J ; Adlard, J ; Barwell, J ; Ong, K-R ; Snape, K ; Walker, L ; Izatt, L ; Side, L ; Rogers, MT ; Porteous, ME ; Ahmed, M ; Morrison, PJ ; Brennan, P ; Eeles, R ; Davidson, R ; Sexton, A ; Christian, A ; Trainer, A ; Spigelman, A ; Fellows, A ; Shelling, A ; De Fazio, A ; Blackburn, A ; Crook, A ; Meiser, B ; Patterson, B ; Clarke, C ; Hunt, C ; Scott, C ; Amor, D ; Marsh, D ; Edkins, E ; Salisbury, E ; Haan, E ; Neidermayr, E ; Macrea, F ; Farshid, G ; Lindeman, G ; Trench, G ; Mann, G ; Giles, G ; Gill, G ; Thorne, H ; Hickie, I ; Winship, I ; Flanagan, J ; Kollias, J ; Visvader, J ; Taylor, J ; Burke, J ; Saunus, J ; Forbes, J ; Hopper, J ; French, J ; Tucker, K ; Wu, K ; Phillips, K ; Lipton, L ; Andrews, L ; Lobb, L ; Walker, L ; Kentwell, M ; Spurdle, M ; Cummings, M ; Gleeson, M ; Harris, M ; Jenkins, M ; Young, MA ; Delatycki, M ; Wallis, M ; Burgess, M ; Price, M ; Brown, M ; Southey, M ; Bogwitz, M ; Field, M ; Friedlander, M ; Gattas, M ; Saleh, M ; Hayward, N ; Pachter, N ; Cohen, P ; Duijf, P ; James, P ; Simpson, P ; Fong, P ; Butow, P ; Williams, R ; Kefford, R ; Scott, R ; Milne, R ; Balleine, R ; Dawson, S ; Lok, S ; O'Connell, S ; Greening, S ; Nightingale, S ; Edwards, S ; Fox, S ; Mclachlan, S-A ; Lakhani, S ; Antill, Y ; Aalfs, C ; Meijers-Heijboer, H ; van Engelen, K ; Gille, H ; Boere, I ; Collee, M ; van Deurzen, C ; Hooning, M ; Obdeijn, I-M ; van den Ouweland, A ; Seynaeve, C ; Siesling, S ; Verloop, J ; van Asperen, C ; van Cronenburg, T ; Blok, R ; de Boer, M ; Garcia, EG ; Adank, M ; Hogervorst, F ; Jenner, D ; van Leeuwen, F ; Rookus, M ; Russell, N ; Schmidt, M ; van den Belt-Dusebout, S ; Kets, C ; Mensenkamp, A ; de Bock, T ; van Der Hout, A ; Mourits, M ; Oosterwijk, J ; Ausems, M ; Koudijs, M ; Marsh, D ; Baxter, R ; Yip, D ; Carpenter, J ; Davis, A ; Pathmanathan, N ; Simpson, P ; Graham, D ; Sachchithananthan, M (NATURE RESEARCH, 2020-01-07)
    Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.