Phenotypic CYP2A6 variation and the risk of pancreatic cancer.
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.


METHODS
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.
Kadlubar
Susan
S
Department of Environmental and Occupational Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. sakadlubar@uams.edu
Anderson
Jeffrey P
JP
Sweeney
Carol
C
Gross
Myron D
MD
Lang
Nicholas P
NP
Kadlubar
Fred F
FF
Anderson
Kristin E
KE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism*; D002110:Caffeine / Q000493:pharmacokinetics; D002273:Carcinogens; D016022:Case-Control Studies; D065637:Cytochrome P-450 CYP2A6; D004789:Enzyme Activation; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects; D008875:Middle Aged; D015146:Midwestern United States / Q000453:epidemiology; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D055815:Young Adult
D002273:Carcinogens; D002110:Caffeine; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6