Molecular epidemiology of DNA repair genes in bladder cancer.
Bladder cancer is a common disease, whose major risk factors include smoking and occupational exposure to chemicals. Superficial bladder cancer has significant healthcare cost implications due to the need for repeated cystoscopic surveillance. Chemical carcinogens can undergo metabolic activation and detoxification in the liver and polymorphisms in the relevant genes have been shown to be associated with bladder cancer risk. In addition, DNA repair enzymes are required to repair the DNA damage associated with carcinogen exposure. The main pathways involved are nucleotide excision repair, base excision repair, and double strand break repair. Investigation of individual polymorphisms in DNA repair genes in bladder cancer has yielded few robust positive findings, which is not surprising given the multifactorial nature of the disease. Pathway approaches using novel genotyping technologies will allow more comprehensive studies of multiple polymorphisms in multiple genes. It will also be possible to investigate gene-environment interaction more rigorously than heretofore, using novel statistical methodology, in larger studies and through collaborative efforts within consortia. The results of the genome-wide association studies in bladder cancer are awaited with interest. In the future, genetic tests might be used in the prevention of bladder cancer to encourage lifestyle changes in those at highest risk of developing the disease, and in the treatment of bladder cancer to optimise cure rates whilst minimising morbidity in a cost-effective manner.