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Arachidonic acid and colorectal adenoma risk: a Mendelian randomization study

Authors Isom CA, Shrubsole MJ, Cai Q, Smalley WE, Ness RM, Zheng W, Murff HJ

Received 8 September 2018

Accepted for publication 14 November 2018

Published 18 December 2018 Volume 2019:11 Pages 17—22


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Editor who approved publication: Professor Henrik Toft Sørensen

Chelsea A Isom,1 Martha J Shrubsole,2,3 Qiuyin Cai,2 Walter E Smalley,4,5 Reid M Ness,5 Wei Zheng,2,3 Harvey J Murff3,6

1Department of General Surgery, Vanderbilt University Medical Center, Nashville, TN, USA; 2Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA; 3GRECC, Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN, USA; 4Department of Health Policy, Vanderbilt University Medical Center, Nashville, TN, USA; 5Division of Gastroenterology, Vanderbilt University Medical Center, Nashville, TN, USA; 6Division of General Internal Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN, USA

Background: Previous studies have shown a link between increased dietary intake of arachidonic acid (ARA) and colorectal neoplasms. It has been shown that erythrocyte phospholipid membrane concentrations of ARA are strongly determined by genetic variation. Fatty acid desaturase (FADS) controls the rate limiting step in ARA production, and FADS variant rs174537 has been shown to be responsible for up to 18.6% of the variation seen. To determine if a causal association exists between erythrocyte membrane ARA concentrations and colorectal adenomas, we conducted a Mendelian randomization (MR) analysis using rs174537 as an instrumental variable (IV). MR analysis was chosen because it is less susceptible to bias and confounding.
Patients and methods:
A case-control study was performed using the Tennessee Colorectal Polyps Study. Patients were matched on age, gender, race, facility site, and year of colonoscopy. Cases were defined as any colorectal adenoma on colonoscopy (n=909) and controls were polyp free (n=855). A two-stage logistic regression was conducted using rs174537 as the IV with the dependent variable being the presence of a colorectal adenoma on colonoscopy.
Results: Cases were older (59 vs 57 years of age, P<0.0001), and more likely to use alcohol (47.4% vs 19.8%, P=0.001) and to smoke (77.0% vs 66.9%, P<0.0001). There was no statistically significant difference in: age, sex, alcohol use, body mass index (BMI), or NSAID use when stratified by the rs174537 alleles. Genotype was strongly associated with erythrocyte membrane ARA concentrations (P<0.0001). We found no evidence of an association between our IV (rs174537) and colorectal adenomas (P=0.41).
Conclusion: In our MR study increased erythrocyte ARA concentrations were not associated with the risk of colorectal adenomas.

Keywords: arachidonic acid, Mendelian randomization, adenomas

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