© 2000 by Oxford University Press
Journal of the National Cancer Institute Monographs, No. 27, 125-134,
2000
© 2000 Oxford University Press
Chapter 7: Molecular Epidemiology of Genetic Polymorphisms in Estrogen Metabolizing Enzymes in Human Breast Cancer
Affiliations of authors: P. A. Thompson, Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, Houston; C. Ambrosone, Division of Molecular Epidemiology, National Center for Toxicological Research, Jefferson, AK.
Correspondence to: Patricia Thompson, Ph.D., Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Blvd., Houston, TX 77030.
Epidemiologic studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. For a number of years, the mechanism for estrogens in carcinogenesis was thought to be that of mitotic stimulation, with the growth promotion of ductal epithelial cells harboring precursor mutations in the breast. However, evidence is now available that estrogens may act as initiators of cellular alterations and tumorigenesis. Investigation and measurement of serum levels of estrogens in epidemiologic studies may, therefore, be misleading, because they may reflect levels quite different from those of hormone metabolites to which the target tissue is exposed. Proportions of hormone metabolites may be estimated by evaluation of associations between breast cancer risk and genetic polymorphisms in enzymes involved in hormone metabolism. A number of molecular epidemiologic studies have been conducted to evaluate associations between polymorphic genes involved in steroid hormone metabolism (i.e., CYP17, COMT, CYP1A1, CYP19, GST, and MnSOD) that may account for a proportion of enzymatic variability, and results are discussed in this review. There are strengths and limitations to such an approach, foremost of which may be the lack of insight into the extent to which individual variability in estrogen exposure may be explained by allelic variation. Variability in other endogenous and exogenous factors that impact parent hormones and their metabolites along activation and conjugation pathways may also affect associations in case–control comparisons. This and other possible reasons for inconsistencies in results of molecular epidemiologic studies are discussed. Contributions from population-based studies and those from the laboratory may together move this field ahead and more clearly elucidate the basis of hormonally related cancers, identifying etiologic factors and susceptible populations for preventive strategies.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Chen, M. D. Gammon, S. L. Teitelbaum, J. A. Britton, M. B. Terry, S. Shantakumar, S. M. Eng, Q. Wang, I. Gurvich, A. I. Neugut, et al. Estrogen-biosynthesis gene CYP17 and its interactions with reproductive, hormonal and lifestyle factors in breast cancer risk: results from the Long Island Breast Cancer Study Project Carcinogenesis, April 1, 2008; 29(4): 766 - 771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tanaka, H. Hirata, Z. Chen, N. Kikuno, K. Kawamoto, S. Majid, T. Tokizane, S. Urakami, H. Shiina, K. Nakajima, et al. Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer Cancer Epidemiol. Biomarkers Prev., January 1, 2007; 16(1): 92 - 97. [Abstract] [Full Text] [PDF]
|
|