학술논문
Shared heritability and functional enrichment across six solid cancers.
Document Type
article
Author
Jiang, Xia; Finucane, Hilary K; Schumacher, Fredrick R; Schmit, Stephanie L; Tyrer, Jonathan P; Han, Younghun; Michailidou, Kyriaki; Lesseur, Corina; Kuchenbaecker, Karoline B; Dennis, Joe; Conti, David V; Casey, Graham; Gaudet, Mia M; Huyghe, Jeroen R; Albanes, Demetrius; Aldrich, Melinda C; Andrew, Angeline S; Andrulis, Irene L; Anton-Culver, Hoda; Antoniou, Antonis C; Antonenkova, Natalia N; Arnold, Susanne M; Aronson, Kristan J; Arun, Banu K; Bandera, Elisa V; Barkardottir, Rosa B; Barnes, Daniel R; Batra, Jyotsna; Beckmann, Matthias W; Benitez, Javier; Benlloch, Sara; Berchuck, Andrew; Berndt, Sonja I; Bickeböller, Heike; Bien, Stephanie A; Blomqvist, Carl; Boccia, Stefania; Bogdanova, Natalia V; Bojesen, Stig E; Bolla, Manjeet K; Brauch, Hiltrud; Brenner, Hermann; Brenton, James D; Brook, Mark N; Brunet, Joan; Brunnström, Hans; Buchanan, Daniel D; Burwinkel, Barbara; Butzow, Ralf; Cadoni, Gabriella; Caldés, Trinidad; Caligo, Maria A; Campbell, Ian; Campbell, Peter T; Cancel-Tassin, Géraldine; Cannon-Albright, Lisa; Campa, Daniele; Caporaso, Neil; Carvalho, André L; Chan, Andrew T; Chang-Claude, Jenny; Chanock, Stephen J; Chen, Chu; Christiani, David C; Claes, Kathleen BM; Claessens, Frank; Clements, Judith; Collée, J Margriet; Correa, Marcia Cruz; Couch, Fergus J; Cox, Angela; Cunningham, Julie M; Cybulski, Cezary; Czene, Kamila; Daly, Mary B; deFazio, Anna; Devilee, Peter; Diez, Orland; Gago-Dominguez, Manuela; Donovan, Jenny L; Dörk, Thilo; Duell, Eric J; Dunning, Alison M; Dwek, Miriam; Eccles, Diana M; Edlund, Christopher K; Edwards, Digna R Velez; Ellberg, Carolina; Evans, D Gareth; Fasching, Peter A; Ferris, Robert L; Liloglou, Triantafillos; Figueiredo, Jane C; Fletcher, Olivia; Fortner, Renée T; Fostira, Florentia; Franceschi, Silvia; Friedman, Eitan; Gallinger, Steven J; Ganz, Patricia A
Source
Nature communications. 10(1)
Subject
Language
Abstract
Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (rg = 0.57, p = 4.6 × 10-8), breast and ovarian cancer (rg = 0.24, p = 7 × 10-5), breast and lung cancer (rg = 0.18, p =1.5 × 10-6) and breast and colorectal cancer (rg = 0.15, p = 1.1 × 10-4). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.