Faculty Collaboration Database

Polymorphisms of cytochrome P4501A2 and N-acetyltransferase genes, smoking, and risk of pancreatic cancer. Carcinogenesis 2006 Jan;27(1):103-11

Date

07/01/2005

Pubmed ID

15987714

Pubmed Central ID

PMC1350610

DOI

10.1093/carcin/bgi171

Scopus ID

2-s2.0-29744455626 (requires institutional sign-in at Scopus site)   88 Citations

Abstract

To test the hypothesis that genetic variation in the metabolism of tobacco carcinogens, such as aromatic amines (AA) and heterocyclic amines (HCA), contributes to pancreatic cancer, we have examined genetic polymorphisms of three key enzymes, i.e. cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 and 2 (NAT1 and NAT2), in a hospital-based case-control study of 365 patients with pancreatic adenocarcinoma and 379 frequency-matched healthy controls. Genotypes were determined using PCR-restriction fragment length polymorphism (RFLP) and Taqman methods. Smoking information was collected by personal interview. Adjusted odds ratio (AOR) and 95% confidence interval (CI) was estimated by unconditional multivariate logistic regression analysis. We found that the NAT1 'rapid' alleles were associated with a 1.5-fold increased risk of pancreatic cancer (95% CI: 1.0-2.1) with adjustment of potential confounders. This effect was more prominent among never smokers (AOR: 2.4, 95% CI: 1.4-4.3) and females (AOR: 1.8, 95% CI: 1.0-3.1). Some genotypes were significantly associated with increased risk for pancreatic cancer among smokers, especially heavy smokers (<20 pack years). For example, heavy smokers with the CYP1A2*1D (T-2467delT) delT, CYP1A2*1F(A-163C) C allele, NAT1 'rapid' or NAT2 'slow' alleles had an AOR (95% CI) of 1.4 (0.7-2.3), 1.9 (1.1-3.4), 3.0 (1.6-5.4) and 1.5 (0.8-2.6), respectively, compared with never smokers carrying the non-at-risk alleles. These effects were more prominent in females than in males. The corresponding AOR (95% CI) was 3.1 (1.0-8.0), 3.8 (1.5-10.1), 4.5 (1.6-12.7) and 2.0 (0.8-5.1) for females versus 1.0 (0.4-1.9), 1.1 (0.5-2.4), 2.1 (1.0-4.6) and 1.1 (0.5-2.6) for males. A significant synergistic effect of CYP1A2*1F C allele and NAT1"rapid" alleles on the risk for pancreatic cancer was also detected among never smokers (AOR: 2.9, 95% CI: 1.2-6.9) and among females (AOR: 2.5, 95% CI: 1.1-5.7). These data suggest that polymorphisms of the CYP1A2 and NAT1 genes modify the risk of pancreatic cancer.

Author List

Li D, Jiao L, Li Y, Doll MA, Hein DW, Bondy ML, Evans DB, Wolff RA, Lenzi R, Pisters PW, Abbruzzese JL, Hassan MM

Author

Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adenocarcinoma
Aged
Arylamine N-Acetyltransferase
Carcinoma, Pancreatic Ductal
Case-Control Studies
Cytochrome P-450 CYP1A2
Female
Gene Frequency
Genetic Predisposition to Disease
Genotype
Humans
Isoenzymes
Male
Middle Aged
Odds Ratio
Pancreatic Neoplasms
Phenotype
Polymorphism, Genetic
Risk Factors
Smoking