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Genome-wide meta-analyses of breast, ovarian, and prostate cancer association studies identify multiple new susceptibility loci shared by at least two cancer types

journal contribution
posted on 2023-05-18, 21:23 authored by Kar, SP, Beesley, J, Amin Al Olama, A, Michailidou, K, Tyrer, J, Kote-Jarai, Z, Lawrenson, K, Lindstrom, S, Ramus, SJ, Thompson, DJ, Kibel, AS, Dansonka-Mieszkowska, A, Michael, A, Dieffenbach, AK, Gentry-Maharaj, A, Whittemore, AS, Wolk, A, Monteiro, A, Peixoto, A, Kierzek, A, Cox, A, Rudolph, A, Gonzalez-Neira, A, Wu, AH, Lindblom, A, Swerdlow, A, Ziogas, A, Ekici, AB, Burwinkel, B, Karlan, BY, Nordestgaard, BG, Blomqvist, C, Phelan, C, McLean, C, Pearce, CL, Vachon, C, Cybulski, C, Slavov, C, Stegmaier, C, Maier, C, Ambrosone, CB, Hogdall, CK, Teerlink, CC, Kang, D, Tessier, DC, Schaid, DJ, Stram, DO, Cramer, DW, Neal, DE, Eccles, D, Flesch-Janys, D, Velez Edwards, DR, Wokozorczyk, D, Levine, DA, Yannoukakos, D, Sawyer, EJ, Bandera, EV, Poole, EM, Goode, EL, Khusnutdinova, E, Hogdall, E, Song, F, Bruinsma, F, Heitz, F, Modugno, F, Hamdy, FC, Wiklund, F, Giles, GG, Olsson, H, Wildiers, H, Ulmer, H-U, Pandha, H, Risch, HA, Darabi, H, Salvesen, HB, Nevanlinna, H, Gronberg, H, Brenner, H, Brauch, H, Anton-Culver, H, Song, H, Lim, H-Y, McNeish, I, Campbell, I, Vergote, I, Gronwald, J, Lubinski, J, Stanford, JL, Benitez, J, Doherty, JA, Permuth, JB, Chang-Claude, J, Donovan, JL, Dennis, J, Schildkraut, JM, Schleutker, J, Hopper, JL, Kupryjanczyk, J, Park, JY, Figueroa, J, Clements, JA, Knight, JA, Peto, J, Cunningham, JM, Pow-Sang, J, Batra, J, Czene, K, Lu, KH, Herkommer, K, Khaw, K-T, Matsuo, K, Muir, K, Offitt, K, Chen, K, Moysich, KB, Aittomaki, K, Odunsi, K, Kiemeney, LA, Massuger, LFAG, Liesel FitzgeraldLiesel Fitzgerald, Cook, LS, Cannon-Albright, L, Hooning, MJ, Pike, MC, Bolla, MK, Luedeke, M, Teixeira, MR, Goodman, MT, Schmidt, MK, Riggan, M, Aly, M, Rossing, MA, Beckmann, MW, Moisse, M, Sanderson, M, Southey, MC, Jones, M, Lush, M, Hildebrandt, MAT, Hou, M-F, Schoemaker, MJ, Garcia-Closas, M, Bogdanova, N, Rahman, N, Le, ND, Orr, N, Wentzensen, N, Pashayan, N, Peterlongo, P, Guenel, P, Brennan, P, Paulo, P, Webb, PM, Broberg, P, Fasching, PA, Devilee, P, Wang, Q, Cai, Q, Li, Q, Kaneva, R, Butzow, R, Kopperud, RK, Schmutzler, RK, Stephenson, RA, MacInnis, RJ, Hoover, RN, Winqvis, R, Ness, R, Milne, RL, Travis, RC, Benlloch, S, Olson, SH, McDonnell, SK, Tworoger, SS, Maia, S, Berndt, S, Lee, SC, Teo, S-H, Thibodeau, SN, Bojesen, SE, Gapstur, SM, Kjaer, SK, Pejovic, T, Tammela, TLJ, Dork, TT, Bruning, T, Wahlfors, T, Key, TJ, Edwards, TL, Menon, U, Hamann, U, Mitev, V, Kosma, V-M, Setiawan, VW, Kristensen, V, Arndt, V, Vogel, W, Zheng, W, Sieh, W, Blot, WJ, Kluzniak, W, Shu, X-O, Gao, Y-G, Schumacher, F, Freedman, ML, Berchuck, A, Dunning, AM, Simard, J, Haiman, CA, Spurdle, A, Sellers, TA, Hunter, DJ, Henderson, BE, Kraft, P, Chanock, SJ, Couch, FJ, Hall, P, Gayther, SA, Easton, DF, Chenevix-Trench, G, Eeles, R, Pharoah, PDP, Lambrechts, D

Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10−8 seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type–specific expression quantitative trait locus and enhancer–gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10−5 in the three-cancer meta-analysis.

Strong>Significance: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers.

History

Publication title

Cancer Discovery

Volume

6

Issue

9

Pagination

1053-1067

ISSN

2159-8274

Department/School

Menzies Institute for Medical Research

Publisher

American Association for Cancer Research

Place of publication

United States

Rights statement

Copyright 2016 AACR

Repository Status

  • Restricted

Socio-economic Objectives

Clinical health not elsewhere classified

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    University Of Tasmania

    Categories

    Keywords

    meta-analysisbreastprostateovariancancer

    Licence

    In Copyright

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