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.
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The breast cancer genome-wide association analyses: BCAC is funded by Cancer Research UK [C1287/A16563, C1287/A10118], the European Union’s Horizon 2020 Research and Innovation Programme (grant numbers 634935 and 633784 for BRIDGES and B-CAST, respectively), and by the European Community’s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS).
Due to the large number of funding sources, only the first few are listed in this section. For the complete list of funding sources, please download this article.
The datasets generated during and/or analyzed during the current study are available from the authors on request. Breast cancer: summary results for all variants are available at http://bcac.ccge.medschl.cam.ac.uk/. Requests for further data should be made through the Data Access Coordination Committee (http://bcac.ccge.medschl.cam.ac.uk/). Ovarian cancer: summary results are available from the Ovarian Cancer Association Consortium (OCAC) (http://ocac.ccge.medschl.cam.ac.uk/). Requests for further data can be made to the Data Access Coordination Committee (http://cimba.ccge.medschl.cam.ac.uk/). Prostate cancer: summary results are publicly available at the PRACTICAL website (http://practical.icr.ac.uk/blog/). Lung cancer: genotype data for lung cancer are available at the database of Genotypes and Phenotypes (dbGaP) under accession phs001273.v1.p1. Readers interested in obtaining a copy of the original data can do so by completing the proposal request form at http://oncoarray.dartmouth.edu/. Head/neck cancer: genotype data for the oral and pharyngeal OncoArray study have been deposited at the database of Genotypes and Phenotypes (dbGaP) under accession phs001202.v1.p1. Colorectal cancer: genotype data have been deposited at the database of Genotypes and Phenotypes (dbGaP) under accession number phs001415.v1.p1 and phs001078.v1.p1.
Supplementary Information accompanies this paper at https://doi.org/10.1038/s41467- 018-08054-4.
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.; and Benitez, Javier, "Shared Heritability and Functional Enrichment Across Six Solid Cancers" (2019). Markey Cancer Center Faculty Publications. 139.
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