Phenotypic CYP2A6 Variation and the Risk of Pancreatic Cancer

Overview

Journal JOP

Specialties Endocrinology
Gastroenterology

Date 2009 May 21

PMID 19454817

Citations 18

Authors

Susan Kadlubar

Jeffrey P Anderson

Carol Sweeney

Myron D Gross

Nicholas P Lang

Fred F Kadlubar

Kristin E Anderson

Affiliations

Soon will be listed here.

Abstract

Objective: Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme capable of activating several procarcinogens, including dietary and tobacco-specific nitrosamines, which have been linked to pancreatic cancer. Positive associations between high CYP2A6 activity and lung and colorectal cancers have been reported. This is the first investigation of CYP2A6 activity and pancreatic cancer.

Design: In this case-control study of cancer of the exocrine pancreas, phenotypic CYP2A6 activity was measured using a ratio of urinary caffeine metabolites. Demographic, smoking, dietary and medical information were obtained by questionnaire. CYP2A6 phenotype, which is not influenced by smoking status, was measured for 90 cases and 470 controls.

Results: When modeled as a continuous variable, and adjusted for age, sex, race, education, current smoking status and chronic pancreatitis, the odds ratio (OR) per one unit of the natural log of the CYP2A6 ratio was 1.52 (95% confidence interval, CI: 1.09-2.12). In an adjusted categorical analysis, subjects in the uppermost quartile (based on controls) of CYP2A6 activity, when compared to the lower three quartiles, carried an 80% greater risk of pancreatic cancer (OR=1.80; 95% CI: 1.07-3.02).

Conclusions: High levels of CYP2A6 activity, as measured by a caffeine phenotyping assay, were positively associated with pancreatic cancer in this casecontrol study among a Midwestern U.S. population.

Citing Articles

Membrane Lipid Derivatives: Roles of Arachidonic Acid and Its Metabolites in Pancreatic Physiology and Pathophysiology.

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Susceptibility loci for pancreatic cancer in the Brazilian population.

Aoki M, Stein A, de Oliveira J, Chammas R, Uno M, Bocon de Araujo Munhoz F BMC Med Genomics. 2021; 14(1):111.

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Expression of cytochrome P450 isozyme transcripts and activities in human livers.

Liu J, Lu Y, Corton J, Klaassen C Xenobiotica. 2020; 51(3):279-286.

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Genetic polymorphisms of the drug-metabolizing enzyme cytochrome P450 2A6 in a Tibetan Chinese population.

Xia R, Zhu X, Chen Z, He Y, Kang L, Yuan D Int J Clin Exp Pathol. 2020; 11(10):5024-5033.

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Variation in CYP2A6 Activity and Personalized Medicine.

Tanner J, Tyndale R J Pers Med. 2017; 7(4).

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