The following is an excerpt of a press release issued December 7, 2007, by the American Association for Cancer Research (AACR) during its Sixth Annual International Conference on Frontiers in Cancer Prevention Research being held in Philadelphia. Visit the AACR Web site to read the full press release on the topic of "Lifestyle and Cancer Prevention: Making Choices that Change Cancer Risk."

The press release describes the research of Jeannette Zinggeler Berg, an M.D./Ph.D. student who is completing her graduate training in biochemistry in the laboratory of Cancer Center member Sharon Murphy, Ph.D.

It has long been known that African-American smokers have a harder time giving up cigarettes, and now researchers from the University of Minnesota may have found a potential biochemical explanation.

Investigators discovered that African-American smokers may have significantly lower levels of an enzyme that metabolizes nicotine and nicotine by-products, compared to Caucasians who were exposed to identical nicotine patches. The findings suggest that African Americans may experience higher nicotine levels per cigarette, which would help explain why "quit" rates are lower among this group.

"Smokers adjust their level of smoking to maintain blood levels of nicotine, which are determined in part by rates of nicotine metabolism, and while we can't say from this study that differences in metabolism definitively account for lower quit rates, it could very well have an impact," said Jeannette Zinggeler Berg, an M.D./Ph.D. student in Biochemistry, Molecular Biology, and Biophysics at the University of Minnesota.

In past studies, elevated levels of the nicotine-related molecule, cotinine, have been observed in African-American smokers compared to Caucasian smokers. Cotinine is a direct metabolite of nicotine - a product of nicotine metabolism - and so it is a marker for exposure to tobacco, Berg says. "It is not carcinogenic and is not an addictive component of tobacco, but the more of it a person has in their blood, the more nicotine they have been exposed to," Berg said.

But researchers have debated whether differences in cotinine seen in African Americans is due to the common use of menthol cigarettes by the group, or to the fact that these smokers may be getting more nicotine per cigarette because they are smoking longer or inhaling more deeply.

In this study, Berg and her colleagues examined different markers of nicotine metabolism in 95 daily smokers who, during the study period, were required not to smoke and to wear a nicotine patch. They specifically looked at levels of glucuronides, which represent a pathway by which the liver metabolizes nicotine and cotinine, preparing these chemicals for urinary excretion. A low blood level of glucuronide can indicate an inefficient excretion pathway for nicotine, cotinine, and other substances such as pharmaceutical drugs, Berg says.

At the beginning of the study and after the participants started using the patch, nicotine metabolites were measured in urine samples. Both when subjects were smoking (baseline urine sample at the start of the study) or when they were on the nicotine patch, the percentage of cotinine in the glucuronide form was significantly lower among African Americans compared to Caucasian participants (at the start of the study: 66 percent versus 82 percent; on patch: 41 percent versus 62 percent). Glucuronidation of nicotine was also lower among African Americans compared to white participants on the patch (16 percent versus 30 percent).

"The higher levels of free cotinine seen in past studies between race groups could be explained by lower levels of glucuronide, which helps break down cotinine," Berg said. "If cotinine is a marker of nicotine in the blood, people with higher levels are more likely to have trouble giving up cigarettes."

Researchers are continuing the study by examining racial variation in two glucuronide enzymes in liver samples. "The differences we have seen could be explained by a number of factors, including environmental causes, and we hope to tease these influences apart," Berg said.

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The mission of the American Association for Cancer Research (AACR) is to prevent and cure cancer. Founded in 1907, AACR is the world's oldest and largest professional organization dedicated to advancing cancer research. The membership includes nearly 26,000 basic, translational, and clinical researchers; health care professionals; and cancer survivors and advocates in the United States and more than 70 other countries.

The University of Minnesota Cancer Center is part of the University's Academic Health Center. It is designated a Comprehensive Cancer Center by the National Cancer Institute. To learn more about the Cancer Center and cancer, call 612-624-2620 or toll-free in Minnesota, Iowa, Wisconsin, and the Dakotas at 1-888-CANCER MN (1-888-226-2376); or visit www.cancer.umn.edu.

Media contacts:

AACR: Greg Lester, 267-646-0554, greg.lester@aacr.org
In the press room (December 5-8): 215-409-4766

University of Minnesota Cancer Center: Mary Lawson, Public Relations Director, 612-624-6165, 612-203-0819 (cell), mlawson@umn.edu