Bladder Cancer - A Model Disease for Investigating Genetic and Environmental Effect

Jian-Min Yuan, M.D., Ph.D.
Associate Professor
Division of Epidemiology and Community Health
School of Public Health
Cancer Center
University of Minnesota

Wednesday, March 26th
3:30pm
MoosT 5-125
Minneapolis Campus

Abstract:
Cigarette smoking is a well established risk factor for bladder cancer, accounting for approximately 50% of cases in the United States. Although Chinese and non-Hispanic whites of Los Angeles share similar smoking history, the former experience only one-third the risk of bladder cancer relative to the latter. Arylamines present in tobacco smoke are recognized bladder carcinogens. Oxidation of arylamines catalyzed by hepatic cytochrome P4501A2 (CYP1A2) enzyme, is believed as a critical first step in converting these chemical species to carcinogenic metabolites capable of causing DNA damage to urothelial cells, leading to the development of bladder cancer. Alternatively, arylamines can be detoxified through the N-acetylation pathway regulated by N-acetyltransferases (NATs) or the conjugation to glutathione pathway promoted by glutathione S-transferases (GSTs). To elucidate the role of these genetic factors in bladder carcinogenesis, a large, population-based case-control study of bladder cancer was conducted among non-Asians in Los Angeles, California and among Chinese in Shanghai, China. The study showed that smokers with efficient CYP1A2 are at increased risk whereas those with efficient NATs and GSTs, at reduced risk of bladder cancer. A higher prevalence of deficient NAT2 and efficient CYP1A2 in non-Hispanic whites than in Chinese may explain, at least in part, the elevated rate of bladder cancer in the former than in the latter. With additional measurements of genetically determined factors involved in metabolism of arylamines, in cellular response to oxidative stress, and in DNA repair, a more comprehensive statistical model will allow for an efficient and pathway-driven examination of multiple gene-arylamine interaction in bladder carcinogenesis.

A social tea will be held at 3:00 P.M. in A434 Mayo. All are Welcome.
For more details contact 612-624-4655 or see http://www.biostat.umn.edu/seminar_academic.html