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dc.contributor.authorLindström, Sara
dc.contributor.authorFinucane, Hilary
dc.contributor.authorBulik-Sullivan, Brendan
dc.contributor.authorSchumacher, Fredrick R
dc.contributor.authorAmos, Christopher I
dc.contributor.authorHung, Rayjean J
dc.contributor.authorRand, Kristin
dc.contributor.authorGruber, Stephen B
dc.contributor.authorConti, David
dc.contributor.authorPermuth, Jennifer B
dc.contributor.authorLin, Hui-Yi
dc.contributor.authorGoode, Ellen L
dc.contributor.authorSellers, Thomas A
dc.contributor.authorAmundadottir, Laufey T
dc.contributor.authorStolzenberg-Solomon, Rachael
dc.contributor.authorKlein, Alison
dc.contributor.authorPetersen, Gloria
dc.contributor.authorRisch, Harvey
dc.contributor.authorWolpin, Brian
dc.contributor.authorHsu, Li
dc.contributor.authorHuyghe, Jeroen R
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorChan, Andrew
dc.contributor.authorBerndt, Sonja
dc.contributor.authorEeles, Rosalind
dc.contributor.authorEaston, Douglas
dc.contributor.authorHaiman, Christopher A
dc.contributor.authorHunter, David J
dc.contributor.authorNeale, Benjamin
dc.contributor.authorPrice, Alkes L
dc.contributor.authorKraft, Peter
dc.contributor.authorPanScan, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL-ILCCO
dc.date.accessioned2017-11-28T16:58:21Z
dc.date.available2017-11-28T16:58:21Z
dc.date.issued2017-09
dc.identifier.issn1055-9965
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/269785
dc.description.abstractBackground: Many cancers share specific genetic risk factors, including both rare high-penetrance mutations and common SNPs identified through genome-wide association studies (GWAS). However, little is known about the overall shared heritability across cancers. Quantifying the extent to which two distinct cancers share genetic origin will give insights to shared biological mechanisms underlying cancer and inform design for future genetic association studies.Methods: In this study, we estimated the pair-wise genetic correlation between six cancer types (breast, colorectal, lung, ovarian, pancreatic, and prostate) using cancer-specific GWAS summary statistics data based on 66,958 case and 70,665 control subjects of European ancestry. We also estimated genetic correlations between cancers and 14 noncancer diseases and traits.Results: After adjusting for 15 pair-wise genetic correlation tests between cancers, we found significant (P < 0.003) genetic correlations between pancreatic and colorectal cancer (rg = 0.55, P = 0.003), lung and colorectal cancer (rg = 0.31, P = 0.001). We also found suggestive genetic correlations between lung and breast cancer (rg = 0.27, P = 0.009), and colorectal and breast cancer (rg = 0.22, P = 0.01). In contrast, we found no evidence that prostate cancer shared an appreciable proportion of heritability with other cancers. After adjusting for 84 tests studying genetic correlations between cancer types and other traits (Bonferroni-corrected P value: 0.0006), only the genetic correlation between lung cancer and smoking remained significant (rg = 0.41, P = 1.03 × 10-6). We also observed nominally significant genetic correlations between body mass index and all cancers except ovarian cancer.Conclusions: Our results highlight novel genetic correlations and lend support to previous observational studies that have observed links between cancers and risk factors.Impact: This study demonstrates modest genetic correlations between cancers; in particular, breast, colorectal, and lung cancer share some degree of genetic basis. Cancer Epidemiol Biomarkers Prev; 26(9); 1427-35. ©2017 AACR.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherAmerican Association for Cancer Research (AACR)
dc.subjectPanScan, GECCO and the GAME-ON Network: CORECT, DRIVE, ELLIPSE, FOCI, and TRICL-ILCCO
dc.subjectHumans
dc.subjectNeoplasms
dc.subjectGenetic Predisposition to Disease
dc.subjectRisk Factors
dc.subjectFemale
dc.subjectMale
dc.subjectGenetic Variation
dc.subjectGenome-Wide Association Study
dc.titleQuantifying the Genetic Correlation between Multiple Cancer Types.
dc.typeArticle
prism.endingPage1435
prism.issueIdentifier9
prism.publicationDate2017
prism.publicationNameCancer Epidemiol Biomarkers Prev
prism.startingPage1427
prism.volume26
dc.identifier.doi10.17863/CAM.16693
dcterms.dateAccepted2017-06-06
rioxxterms.versionofrecord10.1158/1055-9965.EPI-17-0211
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2017-09
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.identifier.eissn1538-7755
rioxxterms.typeJournal Article/Review
pubs.funder-project-idNational Cancer Institute (U19CA148537)
pubs.funder-project-idNational Cancer Institute (U19CA148065)
pubs.funder-project-idCancer Research UK (A12014)
cam.issuedOnline2017-06-21
rioxxterms.freetoread.startdate2018-09-01


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