Genome-wide association study identifies possible genetic risk factors for colorectal adenomas

Todd L. Edwards, Martha J. Shrubsole, Qiuyin Cai, Guoliang Li, Qi Dai, Douglas Rex, Thomas Ulbright, Zhenming Fu, Ryan H. Delahanty, Harvey J. Murff, Walter Smalley, Reid M. Ness, Wei Zheng

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Background: Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. Methods: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls.We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. Results: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10-4), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10-6). Conclusions: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. Impact: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.

Original languageEnglish
Pages (from-to)1219-1226
Number of pages8
JournalCancer Epidemiology Biomarkers and Prevention
Volume22
Issue number7
DOIs
StatePublished - Jul 2013

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Genome-Wide Association Study
Adenoma
Colorectal Neoplasms
Polyps
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Histone Deacetylases
Genes
Meta-Analysis
Carcinogenesis
Logistic Models
Genome
Recurrence
Mortality
Growth
Neoplasms

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Genome-wide association study identifies possible genetic risk factors for colorectal adenomas. / Edwards, Todd L.; Shrubsole, Martha J.; Cai, Qiuyin; Li, Guoliang; Dai, Qi; Rex, Douglas; Ulbright, Thomas; Fu, Zhenming; Delahanty, Ryan H.; Murff, Harvey J.; Smalley, Walter; Ness, Reid M.; Zheng, Wei.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 22, No. 7, 07.2013, p. 1219-1226.

Research output: Contribution to journalArticle

Edwards, TL, Shrubsole, MJ, Cai, Q, Li, G, Dai, Q, Rex, D, Ulbright, T, Fu, Z, Delahanty, RH, Murff, HJ, Smalley, W, Ness, RM & Zheng, W 2013, 'Genome-wide association study identifies possible genetic risk factors for colorectal adenomas', Cancer Epidemiology Biomarkers and Prevention, vol. 22, no. 7, pp. 1219-1226. https://doi.org/10.1158/1055-9965.EPI-12-1437
Edwards, Todd L. ; Shrubsole, Martha J. ; Cai, Qiuyin ; Li, Guoliang ; Dai, Qi ; Rex, Douglas ; Ulbright, Thomas ; Fu, Zhenming ; Delahanty, Ryan H. ; Murff, Harvey J. ; Smalley, Walter ; Ness, Reid M. ; Zheng, Wei. / Genome-wide association study identifies possible genetic risk factors for colorectal adenomas. In: Cancer Epidemiology Biomarkers and Prevention. 2013 ; Vol. 22, No. 7. pp. 1219-1226.
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AU - Shrubsole, Martha J.

AU - Cai, Qiuyin

AU - Li, Guoliang

AU - Dai, Qi

AU - Rex, Douglas

AU - Ulbright, Thomas

AU - Fu, Zhenming

AU - Delahanty, Ryan H.

AU - Murff, Harvey J.

AU - Smalley, Walter

AU - Ness, Reid M.

AU - Zheng, Wei

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N2 - Background: Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. Methods: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls.We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. Results: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10-4), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10-6). Conclusions: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. Impact: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.

AB - Background: Colorectal cancer is the second leading cause of cancer-related death, and most colorectal cancer usually arises from colorectal adenomas. Removal of polyps reduces mortality from colorectal cancer. Colorectal adenomas are known to aggregate in families; however, the genetic determinants for risk of polyps are largely unknown. Methods: In this study, we used data from the Tennessee Colorectal Polyp Study and the Tennessee-Indiana Adenoma Recurrence Study to conduct a GWAS of adenoma cases and controls. Our design consisted of discovery and replication phases for a total of 2,551 Caucasian adenoma cases and 3,285 Caucasian controls.We carried out logistic regression to test for association in both the discovery and replication phase and further examined the results with meta-analysis. Results: No single nucleotide polymorphism (SNP) achieved a genome-wide significant P value; however, the most significantly associated SNPs were either previously associated with colorectal cancer in GWAS, such as rs10505477 in the gene POU5F1 [odds ratio (OR) = 0.87; 95% confidence interval (CI) 0.81-0.94; P = 4.4 × 10-4), or have been biologically linked to benign growths in other tissues, such as rs1919314 in the gene histone deacetylase 9 (OR = 1.32; 95% CI, 1.18-1.47; P = 1.1 × 10-6). Conclusions: This study suggests that several SNPs may be related to adenoma risk and provides clues for future studies. Impact: These results suggest that some known genetic risk factors of colorectal cancer are necessary but not sufficient for carcinogenesis.

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