Lifestyle and cancer prevention: Making choices that change cancer risk

December 07, 2007

PHILADELPHIA - How do the lifestyle choices we make affect our chances of developing cancer" Today, at the American Association for Cancer Research's Sixth Annual International Conference on Frontiers in Cancer Prevention Research, being held from December 5 to 8 in Philadelphia, Pennsylvania, researchers will present some answers to questions regarding daily decisions in diet, exercise, smoking and other lifestyle factors.

According to their findings, while genetics and environment are major contributors to cancer risk, the simple decisions made each day often matter too. Whether you are picking up a pack of cigarettes, a bottle of suntan lotion, or your walking pace, studies show the power to influence cancer risk is in your hands.

Diet and physical activity in lung cancer risk prediction for current, former, and never smokers. Abstract no. B143

People who have quit smoking can further reduce their risk of developing lung cancer by adding lots of vegetables to their diet − as measured by eating four or more servings of salads a week − compared to people who quit but do not eat their veggies, report researchers at The University of Texas M. D. Anderson Cancer Center. The investigators also found that physical activity like gardening reduces risk of developing the cancer in "former-smokers" by up to 45 percent, compared to former smokers who don't garden.

"We are trying to understand what components of lifestyle can reduce lung cancer risk in people who have quit smoking − which has been a neglected field of study," said Michele Forman, Ph.D., a professor of epidemiology at the University of Texas. "Although this is a very preliminary analysis, it gives us some important clues about how everyone − smokers and non-smokers alike − might be able to reduce their risk of developing lung cancer."

The research team also found that current smokers have a two-fold higher risk of developing lung cancer if they eat three servings or less of salad a week, compared to current smokers who do eat four or more salads weekly. Reduction of risk through gardening was about the same (33 percent) as seen in former smokers, they found. The investigators are also exploring the role of diet and physical activity in lung cancer risk for never-smokers.

"If you are worried about lung cancer risk, this study shows that you may benefit from eating a healthy diet and being physically active," Forman said.

The data come from M. D. Anderson's case control study of lung cancer, involving more than 3,800 participants. Its unique design matches lung cancer patients at M. D. Anderson with participants who are treated at a Houston HMO and divides them by smoking status. So, for example, a person who has never smoked but who developed lung cancer would be matched with a never-smoker who is cancer-free, and the same pairing process is done for former and current smokers with and without lung cancer. All participants are non-Hispanic whites.

The model has already identified a variety of epidemiologic risk factors for lung cancer due to exposure to second-hand smoke and to dust, family history of cancer, history of respiratory disease in the patient and smoking history. With those variables, the discriminatory power of the model was modest.

This study added diet and physical activity to the list of potential factors, making it the first risk prediction model to address both of these variables at the same time, Forman says. To do that, investigators asked participants about eating salad "because salad is a marker for consumption of many vegetables," and polled participants about gardening activity "because we found that gardening is one of the few activities that people with lung cancer report doing," she said.

According to Forman, the researchers do not know yet whether those habits of eating well and exercising "are a marker for other lifestyle factors that might be even more important, such as lack of alcohol consumption. We have a lot of puzzles in the picture yet to analyze."

Gender differences in antioxidant activity, DNA damage, and vasculature in ultraviolet light exposed skin. Abstract no. B144

A novel study in mice suggests that men are more prone to developing cancer than women because of gender differences in antioxidant levels and the ability to repair DNA damage.

Researchers at Ohio State University found that when exposed to the same degree of damaging ultraviolet (UV) light, the skin of male mice suffered more genetic damage than that of female mice. As a consequence, the male mice developed more squamous cell skin cancers, and these tumors formed faster and grew more aggressively than those that developed in the skin of female mice.

These results may explain why men develop three times as many squamous cell skin cancers as women do, and may also offer a clue as to why men are more prone to cancer development in general, says Kathleen Tober, Ph.D., a research scientist in Ohio State's Department of Pathology.

"Men get more skin cancer than women and it has classically been thought that the reason for this is lifestyle - men spend more time outside and are less likely to use sun protection," Tober said. "Our data suggests that while that may be a factor, an even more critical reason for this difference is that female skin may be better able to combat the damaging effects of UV exposure.

"Based on our data, it would be a reasonable hypothesis that one of the underlying mechanisms for this is that men might have less overall antioxidant levels and diminished DNA repair capacity," she said.

Approximately half of the 2 million-plus cancer cases diagnosed in the U.S. are non-melanoma skin cancers. Squamous cell carcinoma, with 250,000 new cases annually, is the second most common cancer in the country. While it is not always a fatal cancer, it does account for about 2,000 cancer deaths a year.

For years, the project's lead researcher Tatiana Oberyszyn, Ph.D., assistant professor at Ohio State's Department of Pathology has studied gender differences in non-melanoma skin cancer. She and her laboratory had initially discovered through controlled experiments that gender and its associated variables accounted for the difference between male and female rates of developing squamous cell carcinomas.

In this study, the researchers discovered that, to their surprise, male mice had less inflammation following exposure to UV light than did female mice, but they had increased oxidative DNA damage possibly due to insufficient levels of proteins that repair DNA damage.

"When equally exposed to sunlight, female skin turns pink and swells up − two classic signs of a sunburn," Tober said. "Male skin doesn't have as robust of a sunburn response to UV exposure but the genetic damage that male skin incurs is actually greater than female mice.

"Our data tells us that female skin has more antioxidants, compounds that scavenge DNA damaging chemicals, and potentially more mechanisms to repair DNA damage than male skin," she said. "These gender differences suggest that female skin has a higher capacity for repairing sunlight induced DNA damage than does male skin. Without complete repair of this genetic damage, male skin is more prone to skin cancer than is female skin."

These findings suggest that gender may need to be considered when it comes to controlling cancer, the researchers say. "Until those strategies are determined and whether you are male or female, it is best to take caution when it comes to sunlight exposure," Tober said.

Nicotine metabolism among African American and white smokers: Group and intraindividual differences in glucuronidation. Abstract no. B122

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.
The mission of the American Association for Cancer Research 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. AACR marshals the full spectrum of expertise from the cancer community to accelerate progress in the prevention, diagnosis and treatment of cancer through high-quality scientific and educational programs. It funds innovative, meritorious research grants. The AACR Annual Meeting attracts more than 17,000 participants who share the latest discoveries and developments in the field. Special Conferences throughout the year present novel data across a wide variety of topics in cancer research, treatment, and patient care. AACR publishes five major peer-reviewed journals: Cancer Research; Clinical Cancer Research; Molecular Cancer Therapeutics; Molecular Cancer Research; and Cancer Epidemiology, Biomarkers & Prevention. Its most recent publication, CR, is a magazine for cancer survivors, patient advocates, their families, physicians, and scientists. It provides a forum for sharing essential, evidence-based information and perspectives on progress in cancer research, survivorship, and advocacy.

American Association for Cancer Research

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