Skip Navigation



Carcinogenesis Advance Access published online on May 21, 2008
Carcinogenesis, doi:10.1093/carcin/bgn085
This Article
Right arrow Advance Access manuscript (PDF) Freely available
Right arrowOA All Versions of this Article:
29/6/1184    most recent
bgn085v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Google Scholar
Right arrow Articles by Suzuki, H.
Right arrow Articles by Li, D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Suzuki, H.
Right arrow Articles by Li, D.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact journals.permissions@oxfordjournals.org

Interaction of the Cytochrome P4501A2, SULT1A1 and NAT Gene Polymorphisms with Smoking and Dietary Mutagen Intake in Modification of the Risk of Pancreatic Cancer

Hideo Suzuki1, Jeffrey S. Morris2, Yanan Li1, Mark A. Doll5, David W. Hein5, Jun Liu2, Li Jiao4, Manal M. Hassan1, Rena S. Day6, Melissa L. Bondy3, James L. Abbruzzese1 and Donghui Li1,7

1 Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
2 Department of Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
3 Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
4 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland
5 Department of Pharmacology and Toxicology and J. Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, Kentucky
6 The University of Texas School of Public Health, Houston, Texas

7 Requests for reprints: Donghui Li, Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030. Phone: 713-834-6690; Fax: 713-834-6153; E-mail: dli{at}mdanderson.org

Aromatic amines (AAs), N-nitroso compounds (NOCs) and heterocyclic amines (HCAs) are suspected human pancreatic carcinogens. Cytochrome P450 (CYP) 1A2, N-acetyltransferase (NAT) 1, NAT2, and sulfotransferase (SULT) are enzymes involved in the metabolism of these carcinogens. To test the hypothesis that genetic variations in carcinogen metabolism modify the risk of pancreatic cancer (PC), we investigated the effect of single nucleotide polymorphisms (SNPs) of the CYP1A2, NAT1, NAT2, and SULT1A1 gene on modification of the risk of PC in a hospital-based study of 755 patients with pancreatic adenocarcinoma and 636 healthy frequency-matched controls. Smoking and dietary mutagen exposure information was collected by personal interviews. Genotypes were determined using the PCR-RFLP and Taqman methods. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using unconditional multivariate logistic regression analysis. We observed no significant main effects of any of these genes on the risk of PC. The CYP1A2 and NAT1 but not SULT1A1 and NAT2 genotypes showed significant interactions with heavy smoking in women not men. In contrast, a significant interaction between NAT1 genotype and dietary mutagen intake on modifying the risk of PC were observed among men but not women. The OR (95% CI) of PC was 2.23 (1.33-3.72) and 2.54 (1.51-4.25) for men having the NAT1*10 and a higher intake of 2-amino-1-methyl-6 phenylimidazo[4,5-b]pyridine (PhIP) and benzo[a]pyrene (BaP), respectively, compared with individuals having no NAT1*10 or a lower intake of these dietary mutagens. These data suggest the existence of gender-specific susceptibility to tobacco carcinogen and dietary mutagen exposure in PC.

Key Words: pancreatic cancer • smoking • dietary mutagen • Cytochrome P4501A2 • NAT • SULT1A1 • sex difference

Received January 28, 2008; revised March 16, 2008; accepted March 21, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
D. Li, H. Suzuki, B. Liu, J. Morris, J. Liu, T. Okazaki, Y. Li, P. Chang, and J. L. Abbruzzese
DNA Repair Gene Polymorphisms and Risk of Pancreatic Cancer
Clin. Cancer Res., January 15, 2009; 15(2): 740 - 746.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.