Tobacco (smoking and
smokeless) use and excessive consumption of alcohol are considered the main risk factors for
oral cancer (ICD9 140-149). Conspicuous national and international variations in
oral cancer incidence and mortality rates, as well as observations in migrant populations, raise the possibility that diet and nutritional status could be an important etiologic factor in oral
carcinogenesis. As shown in this report, abuse of alcohol and tobacco has serious nutritional implications for the host, and generates increased production of reactive
free radicals as well as eliciting immunosuppression. Maintenance of optimal competence of the immune system is critical for
cancer surveillance.
Active oxygen species and other reactive
free radicals mediate phenotypic and genotypic alterations that lead from mutation to
neoplasia. Consequently, the most widely used chemopreventive agents against
oral cancer (e.g.,
vitamins A, E, C, and
beta-carotene) are
anti-oxidants/
free radical scavengers. These
anti-oxidants, both natural and synthetic, neutralize metabolic products (including
reactive oxygen species), interfere with activation of procarcinogens, prevent binding of
carcinogens to
DNA, inhibit
chromosome aberrations, restrain replication of the transformed cell, suppress actions of
cancer promoters, and may even induce regression of precancerous oral lesions such as
leukoplakia and erythroplakia.
Malnutrition is characterized by marked tissue depletion of
anti-oxidant nutrients, including GSH (gamma-glutamyl-
cysteinyl-glycine), a key cellular
anti-oxidant as well as a modulator of T-cell activation. GSH or its precursor
cysteine inhibits activation of the nuclear
transcription factor kB(NFkB), and has been shown to be protective against chemically induced
oral cancer and
leukoplakia. Alcohol-, tobacco-, and/or
malnutrition-induced immunosuppression promotes impaired salivary gland function and oral mucosal immunity, a prominent reduction in the number of helper CD4 cells with less marked changes in number of suppressor T-cells, and depressed NK cell activity, among others. These suggest a breakdown in capacity or the malnourished to mount effective
tumor surveillance. This review article underscores the compounding but important roles of nutritional/dietary factors in the long-established causal link between abuse of alcohol and tobacco (smoking and
smokeless) and
oral cancer.