Carcinogenesis, Vol. 22, No. 2, 209-214,
February 2001
© 2001 Oxford University Press
COMMENTARY |
Single nucleotide polymorphisms, metabolic activation and environmental carcinogenesis: why molecular epidemiologists should think about enzyme expression
Institute of Cancer Research, Haddow Laboratories, Cotswold Road, Sutton, SM2 5NG, UK
This commentary was written to stimulate thoughts on, and consideration of, enzyme expression data in target organs when investigating possible associations between polymorphisms in carcinogen activation enzymes, lifestyle/dietary factors and cancer risk. The lung and breast are taken as examples. There is overwhelming evidence for a genotoxic mechanism in lung cancer development, and compelling evidence for the contribution of genotoxins to breast cancer aetiology. A consistent association has been shown where lung cancer risk is decreased by a G
A polymorphism in the myeloperoxidase (MPO) gene, which is expressed in neutrophils recruited to the lung after chemical or immunological insults. In the breast, a consistent lack of association has been observed for women who are fast N-acetyltransferase type 2 (NAT2) acetylators consuming cooked meat. This could be explained by the lack of detectable NAT2-associated sulfamethazine acetylation activity in cytosols prepared from mammary tissue, suggesting a minor contribution to carcinogen activation. The recent identification in mammary cytosols of detectable sulfotransferase isoforms (SULT1A1 and SULT1A3), which have high catalytic efficiency for activating N-hydroxylated heterocyclic amines (HCAs, mutagens in cooked meat), offers a more important role for these enzymes in the metabolic activation of genotoxins in the breast. The possible contribution of MPO and lactoperoxidase enzymes to carcinogen activation in mammary tissue is also considered. Sulfotransferases and peroxidases have wide substrate specificity in terms of carcinogen activation (HCAs, aromatic amines and polycyclic aromatic hydrocarbons—all present in cooked meat and tobacco smoke) compared with NATs (HCAs and aromatic amines only). For gene–environment interactions, investigations into functional polymorphisms in SULT and peroxidase genes may, therefore, offer new evidence for the involvement of genotoxins in the initiation of carcinogenesis. Identification of the isoforms (if any) of carcinogen activation enzymes that are expressed in the organs of interest will help to determine which genes to investigate in these studies.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Agudo, M. Peluso, N. Sala, G. Capella, A. Munnia, S. Piro, F. Marin, R. Ibanez, P. Amiano, M.J. Tormo, et al. Aromatic DNA adducts and polymorphisms in metabolic genes in healthy adults: findings from the EPIC-Spain cohort Carcinogenesis, June 1, 2009; 30(6): 968 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Cotterchio, B. A. Boucher, M. Manno, S. Gallinger, A. B. Okey, and P. A. Harper Red Meat Intake, Doneness, Polymorphisms in Genes that Encode Carcinogen-Metabolizing Enzymes, and Colorectal Cancer Risk Cancer Epidemiol. Biomarkers Prev., November 1, 2008; 17(11): 3098 - 3107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S Wilbur, D Wohlers, S Paikoff, L. Keith, and O Faroon ATSDR evaluation of health effects of benzene and relevance to public health Toxicology and Industrial Health, June 1, 2008; 24(5-6): 263 - 398. [Abstract] [PDF]
|
|
|
|
 |
|
 A. Husain, X. Zhang, M. A. Doll, J. C. States, D. F. Barker, and D. W. Hein Identification of N-Acetyltransferase 2 (NAT2) Transcription Start Sites and Quantitation of NAT2-Specific mRNA in Human Tissues Drug Metab. Dispos., May 1, 2007; 35(5): 721 - 727. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. L. Goode, J. D. Potter, W. R. Bamlet, D. N. Rider, and J. Bigler Inherited variation in carcinogen-metabolizing enzymes and risk of colorectal polyps Carcinogenesis, February 1, 2007; 28(2): 328 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Jakszyn, A. Agudo, R. Ibanez, R. Garcia-Closas, G. Pera, P. Amiano, and C. A. Gonzalez Development of a Food Database of Nitrosamines, Heterocyclic Amines, and Polycyclic Aromatic Hydrocarbons J. Nutr., August 1, 2004; 134(8): 2011 - 2014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Duell, E. A. Holly, P. M. Bracci, J. K. Wiencke, and K. T. Kelsey A Population-based Study of the Arg399Gln Polymorphism in X-Ray Repair Cross- Complementing Group 1 (XRCC1) and Risk of Pancreatic Adenocarcinoma Cancer Res., August 15, 2002; 62(16): 4630 - 4636. [Abstract] [Full Text] [PDF]
|
|