Carcinogenesis Advance Access published online on March 28, 2006
Carcinogenesis, doi:10.1093/carcin/bgl022
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio 44106-7281, USA
* To whom correspondence should be addressed. To date, the potential impact of hormones on prostate cancer has predominantly focused on receptor mediated events. However, catechol estrogens, if not inactivated by catechol-O-methyltransferase (COMT), can generate large quantities of reactive oxygen species (ROS). ROS may cause a spectrum of damage including oxidative DNA base lesions which can lead to irreversible mutation(s) if they are not repaired by base excision repair (BER) systems. hOGG1 is a key enzyme in short patch BER because it recognizes and performs initial excision of the most common form of oxidative DNA base damage, 8-hydroxyguanine (8-oxo-dG). To investigate potential non-receptor mediated estrogen effects, we evaluated the association between COMT Val158Met and hOGG1 Ser326Cys polymorphisms and prostate cancer in a family-based case-control study (439 prostate cancer cases, 479 brother controls). We observed no noteworthy associations between these polymorphisms and prostate cancer risk in the total study population. However, among men with more aggressive prostate cancer, the hOGG1 326 Cys/Cys genotype was inversely associated with disease (OR=0.30; 95% C.I.= 0.09-0.98). Combining the lower activity CYP1B1 432 Leu/Leu or Leu/Val genotypes (which may decrease the level of catechol estrogens and ROS generated) with the hOGG1 326 Cys/Cys genotype and the XRCC1 399 Arg/Arg or Arg/Gln genotypes (which may enhance BER) resulted in an even further reduced risk in Caucasians with more aggressive disease (OR=0.09; 95% C.I.=0.01-0.56). Including the high activity COMT 158Val allele to this combination also lowered aggressive prostate cancer risk but the effect was not as strong (OR=0.20; 95% C.I.=0.05-0.88). The decreased risk we observed with the hOGG1 326 Cys/Cys genotype confirms an earlier report and the further reduced risk found with the CYP1B1 (432 Leu/Leu or Leu/Val)-hOGG1 (326 Cys/Cys)-XRCC1 (Arg/Arg or Arg/Gln) genotype combination may lend new insights to the importance of ROS generated from non-receptor mediated estrogenic mechanisms in more aggressive prostate cancer.
Received February 3, 2006
Revised March 10, 2006
Accepted March 18, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Polymorphisms in estrogen bioactivation, detoxification and oxidative DNA base excision repair genes and prostate cancer risk
Nora L. Nock 1,
Mine S. Cicek 2,
Li Li 3,
Xin Liu 4,
Benjamin A. Rybicki 5,
Andrea Moreira 6,
Sarah J. Plummer 6,
Graham Casey 6,
and
John S. Witte 4 *
2 Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA
3 Department of Family Medicine, Case Western Reserve University, Cleveland, Ohio 44106, USA
4 Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California 94143-0560, USA
5 Department of Biostatistics and Research Epidemiology, Henry Ford Health System, Detroit, Michigan 48202, USA
6 Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
John S. Witte, E-mail: jwitte{at}itsa.ucsf.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  O. Cussenot, A. R. Azzouzi, N. Nicolaiew, G. Fromont, P. Mangin, L. Cormier, G. Fournier, A. Valeri, S. Larre, F. Thibault, et al. Combination of Polymorphisms From Genes Related to Estrogen Metabolism and Risk of Prostate Cancers: The Hidden Face of Estrogens J. Clin. Oncol., August 20, 2007; 25(24): 3596 - 3602. [Abstract] [Full Text] [PDF]
|
|