Quantifying the genetic correlation between multiple cancer types

Sara Lindström, Hilary Finucane, Brendan Bulik-Sullivan, Fredrick R. Schumacher, Christopher I. Amos, Rayjean J. Hung, Kristin Rand, Stephen B. Gruber, David Conti, Jennifer B. Permuth, Hui Yi Lin, Ellen L. Goode, Thomas A. Sellers, Laufey T. Amundadottir, Rachael Stolzenberg-Solomon, Alison Klein, Gloria Petersen, Harvey Risch, Brian Wolpin, Li HsuJeroen R. Huyghe, Jenny Chang-Claude, Andrew Chan, Sonja Berndt, Rosalind Eeles, Douglas Easton, Christopher A. Haiman, David J. Hunter, Benjamin Neale, Alkes L. Price, Peter Kraft

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1427-1435
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume26
Issue number9
DOIs
StatePublished - Sep 1 2017

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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    Lindström, S., Finucane, H., Bulik-Sullivan, B., Schumacher, F. R., Amos, C. I., Hung, R. J., Rand, K., Gruber, S. B., Conti, D., Permuth, J. B., Lin, H. Y., Goode, E. L., Sellers, T. A., Amundadottir, L. T., Stolzenberg-Solomon, R., Klein, A., Petersen, G., Risch, H., Wolpin, B., ... Kraft, P. (2017). Quantifying the genetic correlation between multiple cancer types. Cancer Epidemiology Biomarkers and Prevention, 26(9), 1427-1435. https://doi.org/10.1158/1055-9965.EPI-17-0211