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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention
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Genetic Colorectal Cancer and Adenoma Risk Variants Are Associated with Increasing Cumulative Adenoma Counts

Brian A. Sullivan, Xuejun Qin, Thomas S. Redding IV, Ziad F. Gellad, Anjanette Stone, David Weiss, Ashton N. Madison, Kellie J. Sims, Christina D. Williams, David Lieberman, Elizabeth R. Hauser and Dawn Provenzale
Brian A. Sullivan
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
2Department of Medicine, Duke University, Durham, North Carolina.
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Xuejun Qin
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
3Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.
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Thomas S. Redding IV
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
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Ziad F. Gellad
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
2Department of Medicine, Duke University, Durham, North Carolina.
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Anjanette Stone
4Cooperative Studies Program Pharmacogenomics Analysis Laboratory, Central Arkansas Veterans Health System, Little Rock, Arkansas.
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David Weiss
5Perry Point Cooperative Studies Program Coordinating Center, Perry Point VA Medical Center, Perry Point, Maryland.
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Ashton N. Madison
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
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Kellie J. Sims
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
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Christina D. Williams
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
2Department of Medicine, Duke University, Durham, North Carolina.
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David Lieberman
6Division of Gastroenterology and Hepatology, School of Medicine, Oregon Health & Science University, Portland, Oregon.
7VA Portland Health Care System, Portland, Oregon.
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Elizabeth R. Hauser
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
3Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina.
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Dawn Provenzale
1Cooperative Studies Program Epidemiology Center, Durham VA Health Care System, Durham, North Carolina.
2Department of Medicine, Duke University, Durham, North Carolina.
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  • For correspondence: dawn.provenzale@va.gov
DOI: 10.1158/1055-9965.EPI-20-0465 Published November 2020
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Abstract

Background: The genetic basis for most individuals with high cumulative lifetime colonic adenomas is unknown. We investigated associations between known colorectal cancer–risk single-nucleotide polymorphisms (SNP) and increasing cumulative adenoma counts.

Methods: The Cooperative Studies Program #380 screening colonoscopy cohort includes 612 selected participants age 50 to 75 with genotyped blood samples and 10 years of clinical follow-up. We evaluated 41 published “colorectal cancer–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.”

Results: Four colorectal cancer–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 of 1.31, 1.29, 1.24, and 1.23, respectively. Three colorectal cancer–risk SNPs were associated with ≥10 cumulative adenomas (P < 0.05), with risk allele odds ratios of 2.09 (rs3184504), 2.30 (rs961253), and 1.94 (rs3217901). A weighted PRS comprised of adenoma-risk SNPs was associated with higher cumulative adenomas (weighted rate ratio = 1.57; P = 0.03).

Conclusions: In this mostly male veteran colorectal cancer screening cohort, several known colorectal cancer–risk SNPs were associated with increasing cumulative adenoma counts and the finding of ≥10 cumulative adenomas. In addition, an increasing burden of adenoma-risk SNPs, measured by a weighted PRS, was associated with higher cumulative adenomas.

Impact: Future work will seek to validate these findings in different populations and then augment current colorectal cancer risk prediction tools with precancerous, adenoma genetic data.

This article is featured in Highlights of This Issue, p. 2105

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Cancer Epidemiol Biomarkers Prev 2020;29:2269–76

  • Received March 30, 2020.
  • Revision received June 25, 2020.
  • Accepted September 4, 2020.
  • Published first September 14, 2020.
  • ©2020 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 29 (11)
November 2020
Volume 29, Issue 11
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Genetic Colorectal Cancer and Adenoma Risk Variants Are Associated with Increasing Cumulative Adenoma Counts
Brian A. Sullivan, Xuejun Qin, Thomas S. Redding IV, Ziad F. Gellad, Anjanette Stone, David Weiss, Ashton N. Madison, Kellie J. Sims, Christina D. Williams, David Lieberman, Elizabeth R. Hauser and Dawn Provenzale
Cancer Epidemiol Biomarkers Prev November 1 2020 (29) (11) 2269-2276; DOI: 10.1158/1055-9965.EPI-20-0465

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Genetic Colorectal Cancer and Adenoma Risk Variants Are Associated with Increasing Cumulative Adenoma Counts
Brian A. Sullivan, Xuejun Qin, Thomas S. Redding IV, Ziad F. Gellad, Anjanette Stone, David Weiss, Ashton N. Madison, Kellie J. Sims, Christina D. Williams, David Lieberman, Elizabeth R. Hauser and Dawn Provenzale
Cancer Epidemiol Biomarkers Prev November 1 2020 (29) (11) 2269-2276; DOI: 10.1158/1055-9965.EPI-20-0465
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