Researchers who analyzed genetic data from patients with bladder cancer discovered three common inherited genetic variants, also known as polymorphisms, which are significantly associated with development of this malignancy.

All three polymorphisms occur in genes that repair DNA damage induced by chemicals in tobacco smoke, and two of them are also associated with damage induced by free radicals, the investigators reported in Cancer Research (2009;69:6857-6864). The findings help reinforce the significant role smoking plays in bladder cancer pathogenesis.

“An important point to consider is that all individuals who smoke should stop doing so, regardless of their genotype,” observed lead investigator Mariana Stern, PhD, Assistant Professor of Preventive Medicine in the Keck School of Medicine at the University of Southern California, Los Angeles. “That is because smoking is a strong risk factor for bladder cancer for all individuals, not just those who have the polymorphisms that we found to be associated with bladder cancer.”

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Dr. Stern and her 47 co-investigators from the International Consortium of Bladder Cancer analyzed the results of 13 studies on genetic polymorphisms associated with bladder cancer. The team focused mostly on 11 studies in which non-Latino whites were the predominant racial or ethnic group.

They found that three polymorphisms in three DNA-repair genes were significantly associated with bladder cancer among non-Latino whites. The odds for developing bladder cancer increased 9 to 10% among carriers of each of these polymorphisms.

One of the polymorphisms was only associated with increased cancer risk among people who were current or past smokers. The other two polymorphisms were associated with increased bladder-cancer risk even among those who had never smoked.

“Therefore, our findings offer further motivation to identify those other sources of carcinogenic exposures, such as hair-dye use, among other exposures” Dr. Stern said. “Follow-up studies from the consortium will try to address that.”

A researcher not involved with the study, Alan Nieder, MD, Assistant Professor of Urology at Columbia University’s Division of Urology in Miami Beach, Fla., said although the new findings show that patients with small DNA polymorphisms may be more susceptible to developing bladder cancer, the increased risk associated with these polymorphisms “are not necessarily clinically significant” compared with the overall risks of developing bladder cancer among smokers versus non-smokers.