Chronic cigarette smoking is associated with diminished folate status

Every year, nearly 300,000 people worldwide are diagnosed with oral cancer.

This type of cancer has the highest incidence in people who use tobacco, including cigarettes, but the means by which tobacco promotes the development of oral cancer is unknown. Researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging (USDA HNRCA) at Tufts University are investigating whether nutritional factors may be involved. A causal link has not been established, but their results provide early insights into the complex relationships among oral cancer, smoking, and two groups of nutrients: folates and select antioxidants.

Folate levels are different in smokers and non-smokers, according to Joel Mason, MD, director of the USDA HNRCA's Vitamins and Carcinogenesis Laboratory and assistant professor at the Friedman School of Nutrition Science and Policy at Tufts. Mason and colleagues, who reported their results in the American Journal of Clinical Nutrition, analyzed the diets and studied blood and cheek cells of 56 men and women between 30 and 80 years of age. Approximately half of these were chronic smokers, defined by a history of smoking at least 10 cigarettes daily for at least the past year.

"Regardless of dietary intake, smokers had lower levels of folate in both blood and cheek cells, compared with non-smokers," says Mason. These findings confirm those of previous studies. Also consistent with previous research results, cheek cells of smokers had significantly more genetic aberrations called micronuclei, which indicate increased risk of oral cancer.

Mason notes that these observations raise the question, "does cigarette smoke promote cancer by depleting cells of folate?" Folate is a B vitamin found in leafy green vegetables and fortified foods that not only helps create and preserve cells, but is also critical for synthesis of DNA; the latter serves as a universal set of blueprints for cells and which, if sufficiently altered, often leads to cancer. "It's possible that diminishing folate in cells may cause the cellular milieu to change, inducing the formation of cancerous cells," says Mason.

"However, based on our findings," Mason says, "it does not appear that folate depletion induced by smoking is a major avenue for the formation of the genetic aberrations (micronuclei) that increase risk of oral cancer." He explains, "Oral micronuclei and low oral folate are each linked with smoking, but they were not related to each other in this study." Mason notes there are other possibly relevant pathways involving folate, however, which were not examined in this study.

In addition to measuring total levels of folate, Mason and colleagues took their analysis a step further. "Folate exists in several different forms, so we also measured the levels of each form present in the cheek cells," corresponding author Jimmy Crott, PhD, scientist in the Vitamins and Carcinogenesis Laboratory at the USDA HNRCA explains. Compared to cheek cells of non-smokers, those of smokers had higher levels of some forms and lower levels of others. Crott stresses that it is not known if the altered distribution of various forms of folate contribute to carcinogenesis. "However," he continues, "it is thought that imbalances in different forms of folate may partly explain why low folate availability enhances cancer risk."