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Genetic Colorectal Cancer and Adenoma Risk Variants are Associated with Increasing Adenoma Counts.

Authors
  • Sullivan, Brian A1
  • Qin, Xuejun1
  • Redding, Thomas S1
  • Gellad, Ziad F1
  • Stone, Annjanette2
  • Weiss, David3
  • Madison, Ashton N1
  • Sims, Kellie J1
  • Williams, Christina D4
  • Lieberman, David5
  • Hauser, Elizabeth R1
  • Provenzale, Dawn6
  • 1 Cooperative Studies Program Epidemiology Center, Durham VA Health Care System.
  • 2 Pharmacogenomic Laboratory, Central Arkansas Veterans Healthcare System.
  • 3 Perry Point Cooperative Studies Program Coordinating, Perry Point VA Medical Center.
  • 4 Cooperative Studies Program Epidemiology Center, Durham VA Medical Center.
  • 5 Medicine-GI, Oregon Health Sciences University.
  • 6 Cooperative Studies Program Epidemiology Center, Durham VA Health Care System [email protected]
Type
Published Article
Journal
Cancer Epidemiology Biomarkers & Prevention
Publisher
American Association for Cancer Research
Publication Date
Sep 14, 2020
Identifiers
DOI: 10.1158/1055-9965.EPI-20-0465
PMID: 32928932
Source
Medline
Language
English
License
Unknown

Abstract

The genetic basis for most individuals with high cumulative lifetime colonic adenomas is unknown. We investigated associations between known colorectal cancer (CRC)-risk single nucleotide polymorphisms (SNPs) and increasing cumulative adenoma counts. The Cooperative Studies Program #380 screening colonoscopy cohort includes 612 selected participants age 50-75 with genotyped blood samples and 10 years of clinical follow up. We evaluated 41 published 'CRC-risk SNPs' for associations with individual cumulative adenoma counts or having ≥10 cumulative adenomas. SNPs were analyzed singly or combined in a polygenic risk score (PRS). The PRS was constructed from eight published SNPs associated with multiple adenomas, termed 'adenoma-risk SNPs.' Four CRC-risk SNPs were associated with increasing cumulative adenoma counts (p<0.05): rs12241008 (gene: VTI1A), rs2423279 (BMP2/HAO1), rs3184504 (SH2B3), and rs961253 (FERMT1/BMP2), with risk allele risk ratios (RR) of 1.31, 1.29, 1.24, and 1.23, respectively. Three CRC-risk SNPs were associated with 10+ cumulative adenomas (p<0.05), with risk allele odds ratios (OR) of 2.09 (rs3184504), 2.30 (rs961253), and 1.94 (rs3217901). A weighted adenoma-risk SNP PRS was associated with higher cumulative adenomas (weighted RR 1.57, p=0.03). In this mostly male Veteran CRC screening cohort, several known CRC-risk SNPs were associated with increasing cumulative adenoma counts and the finding of 10+ cumulative adenomas. Additionally, an increasing burden of adenoma-risk SNPs, measured by a weighted PRS, was associated with higher cumulative adenomas. Future work will seek to validate these findings in different populations, and then augment current CRC risk prediction tools with precancerous, adenoma genetic data. Copyright ©2020, American Association for Cancer Research.

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