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Cancer Epidemiol Biomarkers Prev. 2017 Sep;26(9):1427-1435. doi: 10.1158/1055-9965.EPI-17-0211. Epub 2017 Jun 21.

Quantifying the Genetic Correlation between Multiple Cancer Types.

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Department of Epidemiology, University of Washington, Seattle, Washington.
Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.
Program in Genetic Epidemiology and Statistical Genetics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts.
The Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, Massachusetts.
Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio.
Seidman Cancer Center, University Hospitals, Cleveland, Ohio.
Department of Community and Family Medicine, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Department of Cancer Epidemiology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
Department of Gastrointestinal Oncology, Moffitt Cancer Center and Research Institute, Tampa, Florida.
Department of Biostatistics and Bioinformatics, Moffitt Cancer Center, Tampa, Florida.
Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, U.S. Department of Health and Human Services, Bethesda, Maryland.
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
Department of Pathology, Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins School of Medicine, Baltimore, Maryland.
Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
Division of Genetics and Epidemiology, The Institute of Cancer Research, and Royal Marsden NHS Foundation Trust, London, United Kingdom.
Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Cambridge, United Kingdom.
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.


Background: 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.

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