According to the American Cancer Society, smokers are six times more likely than nonsmokers to develop oral cavity and oropharyngeal cancers. The mechanisms of tobacco-associated carcinogenesis are quite well established, and investigators agree that carcinoma may form as a result of tobacco-induced damage to the DNA in the cells lining the oral cavity. Heavy alcohol use is another major risk factor for oral cancer in developed countries, and chronic smoking and excessive alcohol consumption comprise a particularly damaging combination.1
Especially for oral cancer, then, prevention of disease hinges on avoiding known carcinogens. Could there be an additional way to counterbalance the damage done by smoking? Investigators worldwide have, for the past two decades, explored the possible protective effect of diet against the development of cancer. Studies by epidemiologists in Italy have consistently found that diets rich in fresh fruits and vegetables appear to be related to lowered risk of several cancers, among them oral, colorectal, and other digestive tract cancers. Does this protective effect of foods containing micronutrients such as folates, antioxidants, and carotenoids extend to smokers? Should findings from studies of micronutrients modify the counseling messages otolaryngologists convey to their patients who smoke?
Studies of Links
Such studies as the 2006 meta-analysis in the American Journal of Clinical Nutrition, published by Pavia et al., have shown that consuming fresh fruits and vegetables is associated with a reduced risk of oral cancer.2 Carlo LaVecchia, MD, MSc, Director of the Laboratory of Epidemiology at Istituto di Recerche Farmacologiche Mario Negri in Milan, Italy, has investigated the link between diet and cancer risk for almost 20 years. He stated that “the relationship between diet and oral cancer is much stronger than that for breast or for colorectal cancer.” But, he said, “this is not strange. Any carcinogen or anticarcinogen that is contained in food will first make contact in the oral cavity, so it is easily understood.” And, more important, he asserted, even adjusting for the two major risk factors of tobacco and alcohol, the association between diet and risk of oral cancer is “strong and consistent.”
Erich M. Sturgis, MD, MPH, Associate Professor in the Departments of Head and Neck Surgery and Epidemiology at the University of Texas M.D. Anderson Cancer Center, believes it’s difficult to separately measure the contributions of diet and smoking when trying to ferret out cancer risk. One problem with case-control studies is that investigators often rely on participants’ self-reporting on diet questionnaires to reflect many years of nutritional exposure, he said. Whether some of the apparent effect of diet is indeed due to the confounding effects of tobacco and alcohol—because heavy drinkers and heavy smokers have a poorer diet—is subject to discussion. Another confounding factor is the genetic variation in metabolism of folates and other nutrients among members of the population, said Dr. Sturgis. For instance, a genetic propensity for folate metabolism that increases the levels in one person may mean that he or she could tolerate smoking-induced lower folate levels, and thus be at a lower-than-expected risk of developing oral cancer.
In April, a group of investigators at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University published results from two studies investigating micronutrient levels in smokers versus nonsmokers in the American Journal of Clinical Nutrition and Cancer Epidemiology, Biomarkers and Prevention.3,4 In the first study, researchers measured dietary, biochemical, and molecular correlates of folate status in 35 healthy smokers and 21 nonsmokers. After adjustment for dietary differences, the team found that smokers had lower concentrations of folate in the blood and particularly in buccal mucosal cells (the latter amounted to a 50% decrease) than the nonsmokers in the study. In addition, the smokers had lower plasma levels of vitamins B6 and B12 than did nonsmoking study participants. The micronucleus index, an indicator of genetic damage and a surrogate biomarker of cancer risk, was twice as high in the buccal mucosal cells of the smokers as compared to levels from the nonsmokers in the study. However, noted principal investigator Joel B. Mason, MD, Associate Professor of Medicine and Nutrition at Tufts, he and his colleagues were unable to establish a correlation between the diminished folate levels and the presence of micronuclei in the study’s smoking participants. “We found that smoking vastly alters the metabolism of this B vitamin, folate, in the mouth, in a number of ways. But we did not see a connection between these altered levels of folate and the biomarker for cancer that we examined,” he said from his Boston office.
The companion study, using the same 56 participants, established that the chronic cigarette smokers also had lower concentrations of most carotenoids and alpha-tocopherol, but higher concentrations of gamma-tocopherol than nonsmokers. (Alpha-tocopherol and gamma-tocopherol are both forms of vitamin E.) Again, there was no concordance between oral concentrations of the micronutrients and evidence of genetic damage (i.e., micronuclei) in the buccal mucosal cells. Dr. Mason pointed out that the studies’ results do not currently translate into practical recommendations. It is not clear whether replacing micronutrients in smokers, through supplements or dietary interventions, could lower their cancer risk.
Dr. Sturgis commented, “The overwhelming cause of oral cancers is smoking, and the only proven effective way to try to prevent these cancers is to stop smoking. Of course, we all recommend healthy diets, but we don’t have a magic folate pill or other micronutrient supplements that could erase the deleterious effects of smoking.”
Cessation First
The sources interviewed agreed that cessation counseling should top the list of physicians’ messages to patients who smoke. “Continuing to smoke is never a good idea,” said Dr. LaVecchia, and dietary measures, no matter how healthy, cannot replace quitting smoking as a frontline defense against oral cancer.
“Stopping smoking is clearly the first thing to do for any smoker,” he said. Former smokers continue to have an excess of cancer risk for several years after quitting, he added. “So, if there is a good time to increase fruit and vegetable consumption, it is when you stop smoking. You can spare some calories and avoid the increase of weight which is common when you stop smoking, and also reduce your risk of upper digestive and respiratory tract cancers.”
The residual risk of developing cancer seen in former smokers might warrant otolaryngologists advising patients to eat a diet “replete with several servings of fresh fruits or vegetables during the course of the day,” said Dr. Mason. “It is reasonable for former smokers to incorporate whatever lifestyle changes they can make into their lives that are going to potentially reduce or eliminate that risk. And, there’s very little downside to recommending a diet enriched with fresh fruits and vegetables. Although we haven’t proven beyond a shadow of a doubt that that can be protective, there certainly are many outstanding epidemiological studies that suggest that is helpful.”
References
- American Cancer Society. Cancer Facts and Figures 2003. © 2003, the American Cancer Society; available online at www.cancer.org/downloads/STT/CAFF2003PWSecured.pdf . Accessed October 6, 2006.
[Context Link] - Pavia M, Pileggi C, et al. Association between fruit and vegetable consumption and oral cancer; a meta-analysis of observational studies. Am J Clin Nutr 2006 May; 83(5):1126–34.
[Context Link] - Gabriel HE, Crott JW, et al. Chronic cigarette smoking is associated with diminished folate status, altered folate form distribution, and increased genetic damage in the buccal mucosa of healthy adults. Am J Clin Nutr 2006 April; 83(4):835–41.
[Context Link] - Gabriel HE, Liu Z, et al. A comparison of carotenoids, retinoids and tocopherols in the serum and buccal mucosa of chronic cigarette smokers versus non-smokers. Cancer Epidemiol Biomarkers Prev 2006 May;15(5):993–9.
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For Further Reading
- Willett WC, Hu FB. Not the time to abandon the food frequency questionnaire: point. Cancer Epidemiol Biomarkers Prev 2006 Oct;15:1757–8.Kristal AR, Potter JD. Not the time to abandon the food frequency questionnaire: counterpoint. Cancer Epidemiol Biomarkers Prev 2006 Oct;15:1759–60.
©2006 The Triological Society