Hypofolatemia as a risk factor for head and neck cancer

Head and neck cancer (HNSCC) includes squamous cell carcinomas of the oral cavity, pharynx and larynx. Approximately 38,500 cases of HNSCC are estimated to occur in the USA in 2004, with 11,000 deaths. HNSCCs represent about 3% of all malignant tumors in the USA. However, in other parts of the world, as India, Southeast Asia or Brazil, the disease is much more prevalent. The standard therapeutic approach, focused on surgery, irradiation and chemotherapy, alone or in combination, has been in part modified in the last 30 years, but the overall survival of HNSCC patients has not substantially improved. To characterize and thus identify high-risk mucosal areas and preclinical tumors, molecular abnormalities in head and neck carcinogenesis have been extensively studied. Metabolic aspects in head and neck carcinogenesis have been less extensively studied. Nevertheless, we know that metabolic alterations, often aspecific, are frequently associated with cancer. These may be secondary or may precede tumor development and favorite progression. In particular, based upon our results, a role for folate deficiency as a risk factor in head and neck carcinogenesis seems plausible. A chemoprevention protocol with folate is at present feasible and ethically correct and is already in progress at our institution. Homocysteine levels in cancer patients are probably largely affected by the HNSCC phenotype. An accumulation of homocysteine might reveal a genetic defect which is theoretically a target for pharmacological therapy, for example by antifolic drugs.