Project 8:

Molecular Epidemiology of Arsenic and Bladder Cancer

Project leader: Karl Kelsey
Project co-leader: Margaret Karagas

Background:

Arsenic is a unique environmental contaminant 1) because it is recognized as a human carcinogen, but does not cause cancer in animal studies, and 2) because it does not cause gene mutations, but does damage DNA and is associated with abnormalities of chromosomes. These unique properties of arsenic suggest that its cancer-causing mechanisms differ from those of other environmental carcinogens.

Specific aim:

In this study researchers investigated the effects of arsenic exposure on bladder cancer. They sought to understand the special mechanism by which arsenic appears to cause cancer. Specifically, the researchers want to learn if arsenic exposure is associated with cancer when additional exposures are present and/or when particular genes show mutations.

Methods:

The study was undertaken partnership with researchers at the Dartmouth College Superfund Program.

Researchers recruiting New Hampshire residents to the study who had been diagnosed with bladder cancer and, a comparison group of New Hampshire residents who do not have bladder cancer. All participants will

• Participate in interviews and surveys to provide their medical, residential, job and exposure histories as well as demographic and lifestyle information, and
• Provide blood and toenail samples as well as a water sample from their drinking water supply.

Results:

• Exposure to arsenic enhances the mutation of genes which in turn was caused by exposure to ultraviolet (UV) radiation Skin cancer risk is increased.
• Exposure to arsenic and exposure to hair dye are associated with bladder cancer.

Recent publications:

• Danaee, H., H.H. Nelson, H. Liber, J.B. Little, and K.T. Kelsey. 2004. Low dose exposure to sodium arsenite synergistically interacts with UV radiation to induce mutations and alter DNA repair in human cells. Mutagenesis 19:143-148.

• Kelsey, K.T., S. Park, H. H. Nelson, and M.R. Karagas. 2004. A population-based case-control study of the XRCC1 Arg399Gln polymorphism and susceptibility to bladder cancer. Cancer Epidemiol. Biomarkers Prev. 13:337-1341.

• Kelsey, K. T., T. Hirao, A. Schned, S. Hirao, T. Devi-Ashok, H. H. Nelson, A. Andrew, and M.R. Karagas. 2004. A population-based study of immunohistochemical detection of p53 alteration in bladder cancer. Br. J. Cancer 90:1572-1576.

• Ryan, L., W. Huang, S.W. Thurston, K.T. Kelsey, J.K. Wiencke, J. K., and D.C. Christiani. 2004. On the use of biomarkers for environmental health research. Stat. Methods Med. Res. 13:207-225.