Systematic evaluation of cancer-specific genetic risk score for 11 types of cancer in The Cancer Genome Atlas and Electronic Medical Records and Genomics cohorts

Cancer Med. 2019 Jun;8(6):3196-3205. doi: 10.1002/cam4.2143. Epub 2019 Apr 9.


Background: Genetic risk score (GRS) is an odds ratio (OR)-weighted and population-standardized method for measuring cumulative effect of multiple risk-associated single nucleotide polymorphisms (SNPs). We hypothesize that GRS is a valid tool for risk assessment of most common cancers.

Methods: Utilizing genotype and phenotype data from The Cancer Genome Atlas (TCGA) and Electronic Medical Records and Genomics (eMERGE), we tested 11 cancer-specific GRSs (bladder, breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, prostate, renal, and thyroid cancer) for association with the respective cancer type. Cancer-specific GRSs were calculated, for the first time in these cohorts, based on previously published risk-associated SNPs using the Caucasian subjects in these two cohorts.

Results: Mean cancer-specific GRS in the population controls of eMERGE approximated the expected value of 1.00 (between 0.98 and 1.02) for all 11 types of cancer. Mean cancer-specific GRS was consistently higher in respective cancer patients than controls for all 11 types of cancer (P < 0.05). When subjects were categorized into low-, average-, and high-risk groups based on cancer-specific GRS (<0.5, 0.5-1.5, and >1.5, respectively), significant dose-response associations of higher cancer-specific GRS with higher OR of respective type of cancer were found for nine types of cancer (P-trend < 0.05). More than 64% subjects in the population controls of eMERGE can be classified as high risk for at least one type of these cancers.

Conclusion: Validity of GRS for predicting cancer risk is demonstrated for most types of cancer. If confirmed in larger studies, cancer-specific GRS may have the potential for developing personalized cancer screening strategy.

Keywords: age at diagnosis; cancer; genetic risk score.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Electronic Health Records*
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genome, Human*
  • Genomics* / methods
  • Genotype
  • Humans
  • Male
  • Neoplasms / diagnosis
  • Neoplasms / epidemiology*
  • Neoplasms / genetics*
  • Odds Ratio
  • Polymorphism, Single Nucleotide
  • Public Health Surveillance