BETHESDA, Md., Aug. 19-Two genetic mutations that appear to put people at increased risk for developing bladder cancer could account for about 31% of bladder cancers, say Spanish and American researchers.
In a large study conducted among patients with bladder cancer in Spain, those found to be missing both copies of a gene that helps to neutralize carcinogens had nearly double the risk of developing bladder cancer as those with two intact copies, reported Montserrat Garcia-Closas, M.D., and colleagues of the National Cancer Institute here and centers in Spain and the U.S.
Patients with only one copy of the gene had about a 20% greater risk for bladder cancer, according to results of the study published in the Aug. 20 issue of The Lancet.
Patients who had a variant form of a second carcinogen-detoxifying gene had about a 40% greater risk for developing transitional cell carcinoma (TCC) of the bladder, and this elevated risk was especially great among cigarette smokers, reported Dr. Garcia-Closas and colleagues.
“These findings provide compelling evidence for the role of common polymorphisms in the etiology of cancer,” Dr. Garcia-Closas and colleagues wrote. “Although the relative risks are modest, these polymorphisms could account for up to 31% of bladder cancers because of their high prevalence.”
The American Cancer Society estimates that there were 60,240 new cases of bladder cancer in the United States in 2004, occurring nearly three times more frequently in men than in women. Bladder cancer accounted for an estimated 12,710 deaths in the U.S. last year.
Both cigarette smoking and workplace exposure to the class of chemicals known as aromatic amines have been linked to increased bladder cancer risk. These chemicals, which are also found in tobacco smoke, are widely used in the manufacture of paints, pharmaceuticals, plastics and agricultural chemicals.
The association between amine exposure and bladder cancer points to genes that encode for proteins that lie along pathways for amine metabolism, noted Emanuela Taioli, M.D., Ph.D., and Sara Raimondi, Ph.D., of the Fondazione Policlinico IRCCS in Milan, Italy, in an accompanying commentary.
“The issue is whether patients carrying unfavorable polymorphisms in these genes are at a higher risk of bladder cancer than patients with more favorable combinations of genetic polymorphism, given the same level of environmental exposure,” they wrote.
To determine whether this was so, Dr. Garcia-Closas and colleagues looked for mutations in genes that normally detoxify carcinogens: glutathione S-transferase M1, or GSTM1, and N-acetyltransferase-2, or NAT2.
They did this by looking for polymorphisms among 1,150 Spanish patients with TCC, and 1,149 controls, all of whom were white. They also performed meta-analyses on various studies looking at links between NAT2 and GSTM1 and bladder cancer.
They found that the odds ratio for bladder cancer for people with deletion of one GSTM1 allele was 1.2 (95% CI 0.8-1.7); for people with deletion of both alleles (GSTM1 null) the odds ratio was 1.9 (1.4-2.7, p for trend