October 7, 2004 —MIT researchers and colleagues have identified three new chemical risk factors for bladder cancer in a study involving some 600 people in the Los Angeles area. The work was reported in the Oct. 6 issue of the Journal of the National Cancer Institute.
The newly discovered carcinogens are found in cigarette smoke, which is already known to be a major cause of bladder cancer, contributing to at least 50 percent of the approximately 60,000 cases in the United States every year.
All three of the new carcinogens, however, were also found to be risk factors for bladder cancer in nonsmokers. Although second-hand smoke is one source of exposure for non-smokers, the researchers say that it is very important to identify the other sources of exposure for nonsmokers.
"Identifying the non-smoking related sources of these [carcinogens] should become a high scientific priority," write the authors, who are led by Professor Steven R. Tannenbaum, Professor of Toxicology at MIT.
"This is very important from a public health point of view," said Tannenbaum, who works in both the Biological Engineering (BE) Division and the Department of Chemistry. "It's much more effective to prevent cancer rather than treat it."
The team also identified six chemicals in the same chemical family that do not appear to be human carcinogens. Because they are chemically similar to their three noxious cousins, they could potentially lead to safer alternatives for the latter.
In 1993 Tannenbaum and other members of his team joined the ongoing Los Angeles Bladder Cancer Study. Among other conclusions, that study has since identified a compound in the arylamine family that is a risk factor for bladder cancer in nonsmokers.
In 2001, researchers at the University of Southern California School of Medicine in Los Angeles analyzed data from 897 patients with bladder cancer and and compared it with data from 897 individuals without bladder cancer. The found an assoociation between bladder cancer and use of permanent hair dyes:
- People who used hair dye at least once a month were twice as likely to develop bladder cancer as those who did not use hair dye.
- People who used permanent hair dyes once a month or more for 15 years were three times as likely to develop bladder cancer as those who never used hair dye.
- Individuals who worked as hairstylists for 10 or more years were five times more likely to develop bladder cancer than individuals who were never exposed to hair dye.
A followup study from USC/ Norris Cancer Center compared 159 women in the Los Angeles Bladder Cancer Study with 164 controls (people without bladder cancer). They looked for genetic differences in the individuals' reaction to bladder-cancer causing arylamines in hair dyes.
In the recent the researchers extended the Los Angeles study to examine "the possible relationship between bladder cancer  and nine other commonly occurring and structurally related arylamines," according to their paper.
Specifically, they analyzed blood samples from some 600 of the people involved in the study. Half had bladder cancer; the others did not but were matched against their counterparts for such things as age, sex and neighborhood.
The team then measured exposure to the arylamines via a technique developed by Tannenbaum's team more than 25 years ago. Arylamines to which a person is exposed react with a protein in the blood, resulting in specific products that can be detected and measured via mass spectrometry.
"So what popped out of this was actually pretty startling," Tannenbaum said. "Three of the nine compounds were indeed found to be significant risk factors for bladder cancer in nonsmokers. And except for one, none of those nine had ever been investigated before" for their potential carcinogenic activity, Tannenbaum said.
This work was sponsored by the National Institutes of Health through the National Cancer Institute and the National Institute of Environmental Health Sciences.
Authors of the paper from MIT are Tannenbaum, Paul L. Skipper, a BE principal research scientist, and Jinping Gan, a former graduate student. Their colleagues Manuela Gago-Dominguez, Kazuko Arakawa, Ronald K. Ross, and Mimi C. Yu are at the University of Southern California, Los Angeles.
acetylase (acet·y·lase) an enzyme that catalyzes the addition or removal of an acetyl group; the most common are acetyltransferases.
acetylation (acet·y·la·tion) the introduction of an acetyl group into the molecule of an organic compound.
acetylator (acet·y·la·tor) an organism capable of metabolic acetylation; in man, acetylator status (fast or slow) is determined by the rate of acetylation of sulfamethazine.
| Arylamine Exposure Related To Bladder Cancer Risk |
Oct. 5, 2004 BETHESDA, Md. (National Cancer Institute) -- Exposure to a family of carcinogens called arylamines is associated with bladder cancer risk in both smokers and nonsmokers, according to a new study in the October 6 issue of the Journal of the National Cancer Institute. Arylamines are found in cigarette smoke, permanent hair dyes, and other environmental sources. Cigarette smoking is an established risk factor for bladder cancer and suspected to play a role in at least half of all U.S. bladder cancer cases. Several arylamine compounds are found in cigarette smoke and are believed to be the source of the risk. However, exposure to an arylamine called 4-ABP is a risk factor for bladder cancer among nonsmokers. To examine the possible relationship between bladder cancer risk and nine other members of the arylamine family, Paul L. Skipper, Ph.D., of the Massachusetts Institute of Technology in Cambridge, Mass., and colleagues conducted a caseÂcontrol study of about 300 bladder cancer patients and about 300 control subjects. They measured exposure to the compounds by measuring the levels of arylamineÂhemoglobin adducts -- reaction products that form in red blood cells after exposure to the arylamine compounds. Levels of all but one of the nine arylamineÂhemoglobin adducts were higher in smokers than in nonsmokers, and levels of all nine adducts were higher in the cancer patients than in the control subjects. In addition, higher levels of three individual adducts were associated with bladder cancer risk after adjusting for other potential risk factors, including current cigarette smoking and lifetime smoking history. Higher levels of adducts were also associated with bladder cancer risk in nonsmokers. These results "implicate exposure to arylamines as the causal factor responsible for most cases of bladder cancer in humans," the authors write. "Tobacco smoke as a source of these carcinogenic arylamines is already well known. Therefore, identifying the nonÂsmoking-related sources of these carcinogenic arylamines should become a high scientific priority." |
Original story by Elizabeth A. Thomson, MIT News Office. Edited by J. Strax, Oct 8, 2004
