Certain women, based on their genetic makeup, may be more susceptible than other women to bladder cancer associated with the use of permanent hair dyes, according to study results released April 9 by researchers at the Keck School of Medicine of USC and colleagues.

Female study participants whose bodies could only slowly flush out carcinogens known as arylamines, which are an ingredient of hair dye, had a higher risk of bladder cancer than women whose bodies eliminated the carcinogens more quickly, the investigators reported. The body’s efficiency in removing such toxins depends on whether someone possesses the "fast" or "slow" version of certain key genes.

Researchers presented results at the American Association of Cancer Research’s 93rd annual meeting in San Francisco.

"We believe these results provide further evidence supporting a causal association between permanent hair dye use and bladder cancer risk," said Manuela Gago-Dominguez, researcher in preventive medicine at the Keck School and USC/Norris Comprehensive Cancer Center and lead author of the study. "They implicate the arylamines contained in hair dye solutions as the carcinogenic substances responsible for bladder cancer development in the users of these dyes."

Early in 2001, USC preventive medicine researchers reported that women who use permanent dyes at least once a month for one year or longer have twice the risk of bladder cancer as nonusers. Monthly or more frequent users of 15 or more years experience three times that risk – even after adjusting for smoking, a known risk factor for bladder cancer.

The increase in bladder cancer risk also was observed in people who are exposed to hair dyes in their work, such as barbers and hairdressers. Increased risk was not seen for those who used temporary or semi-permanent dyes.

Gago-Dominguez explained that small amounts of arylamines are absorbed through the skin during the use of hair dye. Certain agents contained in permanent dye might cause more of the arylamines to be absorbed through the skin than in the case of temporary or semi-permanent dyes, some theorize.

Certain important, protective enzymes in the body metabolize those arylamines, trying to render them harmless. The body expels the chemicals through urine, which passes through the bladder.

The efficiency of these protective enzymes depends on genes that provide the recipe for making the enzymes. The genes come in fast and slow varieties.

The research team looked at 159 female bladder cancer patients in Los Angeles and compared them to 164 similar, healthy women, analyzing their genetic makeup through blood and urine samples.

They found that in women with certain slow genes (the "NAT2 slow" phenotype), exclusive permanent hair dye use was associated with a nearly tripled risk of bladder cancer.

Among women with other slow genes (the "CYP1A2 slow" phenotype), exclusive permanent hair dye use was associated with a 2.5-fold increased risk.

Finally, among nonsmoking women with a third type of slow genes ("NAT1 slow" genotype), exclusive permanent hair dye use was associated with a 6.8-fold increased risk.

Further study is needed to fully understand relationships between hair dyes and bladder cancer, researchers said.

Bladder cancer accounts for 6 percent of all new cancer cases in men and 2 percent of all new cancer cases in women. The American Cancer Society estimates that 56,500 Americans will be diagnosed with the cancer and 12,600 Americans will die from it in 2002.

The research was supported by grants from the National Cancer Institute and the National Institute of Environmental Health Sciences.