Shared heritability and functional enrichment across six solid cancers

Nat Commun. 2019 Jan 25;10(1):431. doi: 10.1038/s41467-018-08054-4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / ethnology
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Case-Control Studies
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / genetics*
  • Colorectal Neoplasms / pathology
  • European Continental Ancestry Group
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Head and Neck Neoplasms / diagnosis
  • Head and Neck Neoplasms / ethnology
  • Head and Neck Neoplasms / genetics*
  • Head and Neck Neoplasms / pathology
  • Humans
  • Inheritance Patterns*
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mental Disorders / ethnology
  • Mental Disorders / genetics
  • Mental Disorders / physiopathology
  • Neoplasm Proteins / genetics
  • Ovarian Neoplasms / diagnosis
  • Ovarian Neoplasms / ethnology
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / pathology
  • Phenotype
  • Polymorphism, Single Nucleotide
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / ethnology
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Smoking / ethnology
  • Smoking / genetics
  • Smoking / physiopathology

Substances

  • Neoplasm Proteins

Grant support