Carcinogenesis Advance Access published online on June 29, 2005
Carcinogenesis, doi:10.1093/carcin/bgi172
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA
* To whom correspondence should be addressed. Tobacco smoking, certain occupational exposures, and exposure to inorganic arsenic in drinking water have been associated with the occurrence of bladder cancer. However, in these tumors the exposure-associated pattern of somatic alterations in genes in the causal pathway for disease has been poorly characterized. In particular, the mechanism by which arsenic induces bladder cancer and the effects of lower environmental levels of exposure remain uncertain. Animal and in-vitro studies have suggested that arsenic and other exposures may act through epigenetic mechanisms. We, therefore, examined, in a population-based study of human bladder cancer, the relationship between epigenetic silencing of three tumor suppressor genes, p16INK4A, RASSF1A, and PRSS3, and exposure to both tobacco and arsenic in bladder cancer. Promoter methylation of each of these genes occurred in approximately 30% of bladder cancers, and both RASSF1A and PRSS3 promoter methylation were associated with advanced tumor stage (P<0.001 and P<0.04, respectively). Arsenic exposure, measured as toenail arsenic, was associated with RASSF1A (P<0.02) and PRSS3 (P<0.1) but not p16INK4A promoter methylation, in models adjusted for stage and other factors. Cigarette smoking was associated with a greater than 2 fold increased risk of promoter methylation of the p16INK4A gene only, with greater risk seen in patients with exposures more recent to disease diagnosis. These results, from human bladder tumors, add to the body of animal and in-vitro evidence that suggests a role in epigenetic alterations for bladder carcinogens.
Received May 27, 2005
Revised June 20, 2005
Accepted June 21, 2005
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Carcinogen exposure and gene promoter hypermethylation in bladder cancer
2 Department of Community and Family Medicine, Dartmouth Medical School, Lebanon, New Hampshire, USA
3 Department of Pathology, Dartmouth Medical School, Lebanon, New Hampshire, USA.
4 Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
5 Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts, USA; Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA
Karl T. Kelsey, E-mail: kelsey{at}hsph.harvard.edu
Abstract 
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  X. Zhou, H. Sun, T. P. Ellen, H. Chen, and M. Costa Arsenite alters global histone H3 methylation Carcinogenesis, September 1, 2008; 29(9): 1831 - 1836. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. M. Wolff, G. Liang, C. C. Cortez, Y. C. Tsai, J. E. Castelao, V. K. Cortessis, D. D. Tsao-Wei, S. Groshen, and P. A. Jones RUNX3 Methylation Reveals that Bladder Tumors Are Older in Patients with a History of Smoking Cancer Res., August 1, 2008; 68(15): 6208 - 6214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Jensen, P. Novak, K. E. Eblin, A. J. Gandolfi, and B. W. Futscher Epigenetic remodeling during arsenical-induced malignant transformation Carcinogenesis, August 1, 2008; 29(8): 1500 - 1508. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Knecht, G. S. Cottrell, S. Amadesi, J. Mohlin, A. Skaregarde, K. Gedda, A. Peterson, K. Chapman, M. D. Hollenberg, N. Vergnolle, et al. Trypsin IV or Mesotrypsin and p23 Cleave Protease-activated Receptors 1 and 2 to Induce Inflammation and Hyperalgesia J. Biol. Chem., September 7, 2007; 282(36): 26089 - 26100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Marsit, E. A. Houseman, A. R. Schned, M. R. Karagas, and K. T. Kelsey Promoter hypermethylation is associated with current smoking, age, gender and survival in bladder cancer Carcinogenesis, August 1, 2007; 28(8): 1745 - 1751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. Marsit, E. A. Houseman, B. C. Christensen, K. Eddy, R. Bueno, D. J. Sugarbaker, H. H. Nelson, M. R. Karagas, and K. T. Kelsey Examination of a CpG Island Methylator Phenotype and Implications of Methylation Profiles in Solid Tumors Cancer Res., November 1, 2006; 66(21): 10621 - 10629. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. M. Ross RE: "CIGARETTE SMOKING AND INCIDENCE OF FIRST DEPRESSIVE EPISODE: AN 11-YEAR, POPULATION-BASED FOLLOW-UP STUDY" Am. J. Epidemiol., November 1, 2006; 164(9): 917 - 918. [Full Text] [PDF]
|
|