Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population

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Background & Aims: The presence of specific single nucleotide polymorphisms (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC), called a genetic risk score (GRS). We investigated whether GRS can identify individuals with clinically relevant neoplasms in a screening colonoscopy population. Methods: We derived a GRS based on 48 SNPs associated with CRC, identified in a comprehensive literature search. We obtained genetic data from 1043 participants (50–79 years old) in a screening colonoscopy study in Germany, recruited from 2005 through 2013 (294 with advanced neoplasms, 249 with non-advanced adenoma (NAAs), and 500 without neoplasms). Each participant was assigned a GRS by aggregating their risk alleles (0, 1, or 2). Risk of advanced neoplasms and NAA according to GRS was calculated by multiple logistic regression. Risk advancement periods were calculated. We replicated our findings using data from a subset of the Tennessee Colorectal Polyp Study. Results: An increased GRS was associated with higher prevalence of advanced neoplasms, but not NAAs. Participants in the middle and upper tertiles of GRS had a 2.2-fold and 2.7-fold increase in risk, respectively, of advanced neoplasms compared to those in the lower tertile. Adjusted odds ratios (ORs) were 1.09 (95% confidence interval [CI], 0.76–1.57) for NAA in the middle tertile and 1.05 (95% CI, 0.70-1.55) for NAA in the upper tertile. The ORs were largest for proximal advanced neoplasms for participants in the middle tertile (OR, 3.55; 95% CI 1.85–6.82) and the upper tertile (OR, 3.61; 95% CI 1.84–7.10). The risk advancement period for medium vs low GRS was 13.4 years (95% CI 4.8–22.0) and for high vs low GRS was 17.5 years (95% CI, 7.8–27.3). Conclusions: In a genetic analysis of participants in a CRC screening study in Germany, an increased GRS (based on CRC-associated SNPs) was associated with increased prevalence of advanced neoplasms. These findings might be used in defining risk-adapted screening ages.


  • Korbinian Weigl
  • Hauke Thomsen
  • Yesilda Balavarca
  • Jacklyn N. Hellwege
  • Martha J. Shrubsole
  • Hermann Brenner
External organisations
  • German Cancer Research Centre
  • Heidelberg University
  • Vanderbilt University
Research areas and keywords


  • Cohort, Colon Cancer, Predisposition, Variant
Original languageEnglish
Article numbere10
Pages (from-to)88-98
Issue number1
Publication statusPublished - 2018 Jul 1
Publication categoryResearch
Externally publishedYes