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Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer.

Publication ,  Journal Article
Suzuki, H; Morris, JS; Li, Y; Doll, MA; Hein, DW; Liu, J; Jiao, L; Hassan, MM; Day, RS; Bondy, ML; Abbruzzese, JL; Li, D
Published in: Carcinogenesis
June 2008

Aromatic amines, N-nitroso compounds and heterocyclic amines 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 polymerase chain reaction-restriction fragment length polymorphism and Taqman methods. Odds ratios (ORs) and 95% confidence intervals (CIs) 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 and benzo[a]pyrene, 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.

Duke Scholars

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

June 2008

Volume

29

Issue

6

Start / End Page

1184 / 1191

Location

England

Related Subject Headings

  • Smoking
  • Sex Factors
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Polymorphism, Restriction Fragment Length
  • Polymerase Chain Reaction
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Mutagens
  • Middle Aged
 

Citation

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Suzuki, H., Morris, J. S., Li, Y., Doll, M. A., Hein, D. W., Liu, J., … Li, D. (2008). Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis, 29(6), 1184–1191. https://doi.org/10.1093/carcin/bgn085
Suzuki, Hideo, Jeffrey S. Morris, Yanan Li, Mark A. Doll, David W. Hein, Jun Liu, Li Jiao, et al. “Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer.Carcinogenesis 29, no. 6 (June 2008): 1184–91. https://doi.org/10.1093/carcin/bgn085.
Suzuki, Hideo, et al. “Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer.Carcinogenesis, vol. 29, no. 6, June 2008, pp. 1184–91. Pubmed, doi:10.1093/carcin/bgn085.
Suzuki H, Morris JS, Li Y, Doll MA, Hein DW, Liu J, Jiao L, Hassan MM, Day RS, Bondy ML, Abbruzzese JL, Li D. Interaction of the cytochrome P4501A2, SULT1A1 and NAT gene polymorphisms with smoking and dietary mutagen intake in modification of the risk of pancreatic cancer. Carcinogenesis. 2008 Jun;29(6):1184–1191.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

June 2008

Volume

29

Issue

6

Start / End Page

1184 / 1191

Location

England

Related Subject Headings

  • Smoking
  • Sex Factors
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Polymorphism, Restriction Fragment Length
  • Polymerase Chain Reaction
  • Pancreatic Neoplasms
  • Oncology & Carcinogenesis
  • Mutagens
  • Middle Aged