Variants in the α-methylacyl-CoA racemase gene and the association with advanced distal colorectal adenoma

Sarah E. Daugherty, Elizabeth A. Platz, Yin Yao Shugart, M. Daniele Fallin, William B. Isaacs, Nilanjin Chatterjee, Robert Welch, Wen Yi Huang, Richard B. Hayes

Research output: Contribution to journalArticlepeer-review

Abstract

Background: α-Methylacyl-CoA racemase (AMACR), an enzyme involved in oxidation of branched chain fatty acids and cholesterol metabolites, as well as ibuprofen metabolism, is overexpressed in colorectal adenomas and cancer. AMACR gene variants have been associated with hereditary prostate cancer, but no studies have evaluated their etiologic role in colorectal carcinogenesis. Methods: We conducted a case-control study of 725 advanced distal colorectal adenoma cases and 729 frequency-matched controls from the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Seven AMACR polymorphisms were genotyped. Unconditional logistic regression models were used to evaluate the associations adjusting for age at randomization and gender. Results: The 201L allele of S201L [TT versus CC: odds ratio (OR), 1.74; 95% confidence interval (95% CI), 1.15-2.62; TC versus CC: OR, 1.17; 95% CI, 0.93-1.49] and the 277E allele of K277E (GG versus AA: OR, 1.66; 95% CI, 1.03-2.68; GA versus AA: OR, 1.21; 95% CI, 0.96-1.53) were associated with increased risk of advanced distal colorectal adenoma (both Ptrend ≤ 0.02); the TGTGCG haplotype of six informative single nucleotide polymorphisms was also associated with increased risk (OR, 1.27; 95% CI, 1.03-1.55). Regular ibuprofen users who were homozygous for the variant allele at either M9V or D175G were at reduced risk for adenoma (both P interaction < 0.05). Conclusion: Our study identified variants in AMACR associated with advanced distal colorectal adenoma and pointed to potential interactions with ibuprofen use.

Original languageEnglish (US)
Pages (from-to)1536-1542
Number of pages7
JournalCancer Epidemiology Biomarkers and Prevention
Volume16
Issue number8
DOIs
StatePublished - Aug 1 2007

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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