Serum folate and homocysteine levels in head and neck squamous cell carcinoma

Cancer. 2002 Feb 15;94(4):1006-11. doi: 10.1002/cncr.10343.


Background: Local and systemic metabolic alterations are always present in cancer. Carcinogenesis is associated with biochemical disorders, often nonspecific, that might promote or derive from tumoral progression. Thus, analysis of metabolic alterations may be a valuable approach to understanding the biochemistry of tumors and may provide a means of identifying new targets for therapy. The methionine cycle in particular has been extensively studied in human cancer.

Methods: The authors analyzed serum concentrations of two metabolites of such pathways, folate and homocysteine, in 42 patients affected by head and neck squamous cell carcinoma (HNSCC) in comparison with two control groups, composed of smokers and non smokers.

Results: Mean folate level was 5.8 +/- 2.1 ng/mL in carcinoma patients, 9.1 +/- 2.7 ng/mL in smoking controls, and 9.7 +/- 2.2 ng/mL in non smoking controls, with a statistically significant difference between carcinoma patients and smokers (mean difference: -3.3 ng/mL; 95% confidence interval [CI]: -4.234 to -2.366; P < 0.0001) and between carcinoma patients and non smokers (mean difference: -3.9 ng/mL; 95% CI: -4.67 to -3.13; P < 0.0001). Mean total homocysteine level was 10.4 +/- 5.3 microM in carcinoma patients, 7.8 +/- 2.5 microM in the non-smokers' group, and 8.3 +/- 2.8 microM in the smokers' group, with statistically significant differences between carcinoma patients and smoking controls (mean difference: 2.1 microM; 95% CI: 0.7056 to 3.494; P = 0.0034) and between carcinoma patients and non smoking controls (mean difference: 2.6 microM; 95% CI: 1.381 to 3.819; P < 0.0001).

Conclusions: Differences in serum levels of folate and homocysteine might arise from tumor development and consequent metabolic alterations or might precede and promote tumor progression. If hypofolatemia is a risk factor for head and neck carcinogenesis, it might suggest a role for folate as a novel chemopreventive agent both in patients with precancerous lesions and in patients with treated HNSCC at risk for loco-regional recurrence and second primary tumors.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Squamous Cell / etiology
  • Carcinoma, Squamous Cell / pathology*
  • Cell Transformation, Neoplastic*
  • Disease Progression
  • Female
  • Folic Acid / blood*
  • Head and Neck Neoplasms / etiology
  • Head and Neck Neoplasms / pathology*
  • Homocysteine / blood*
  • Humans
  • Male
  • Middle Aged
  • Risk Factors
  • Smoking


  • Homocysteine
  • Folic Acid