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Folate in Head and Neck Squamous Cell Cancer Chemoprevention: Purposely Left Out?

Head & Neck Cancer Medical Oncology Unit, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy

Elda Tagliabue

Molecular Biology Unit, Experimental Oncology, Fondazione Istituto di Ricovero e Cura a Carattere Scientifico, Istituto Nazionale dei Tumori, Milan, Italy

To the Editor:

We read with great interest the editorial by Khuri and Shin about chemoprevention strategies in head and neck cancer.¹ The authors widely approached the field, noting the attention on the importance of adopting risk-stratified models.

Curiously, folate was left aside. Folate deficiency due to low intake or to polymorphisms in enzyme metabolizing or storing genes, has been linked to a higher risk of developing head and neck cancer.^2,3 Folate in preventing carcinogenesis acts through maintenance of DNA integrity and stability, reduction of risk of TP53 mutations, and decrease of methylation-mediated p16 inactivation.^4,5 Epidemiologic studies stress the importance of a vegetable-rich dietary pattern, containing an high amount of folate, on cancer prevention. Interestingly, high intake of folate was recognized as protective factor against the subgroup of HER-2–overexpressing breast cancer, attributing to folic acid a role in inhibiting carcinogenesis dependent on epidermal growth factor receptor (EGFR) family receptors.⁶ In colon cancer cell lines, supplemental folic acid inhibited proliferation in a dose-dependent manner, with concurrent reduction of EGFR tyrosin kinase activity and of its ligand transforming growth factor-.⁷ In this context, vitamin supplementation in EGFR dependent tumors such as head and neck cancer deserve further study. Indeed, a phase II study already investigated the effectiveness of 6-month folic acid on laryngeal leucoplakia.⁸ We consider folic acid metabolism an attractive model within biochemopreventive stategies fulfilling the criteria for a risk-stratified approach.

AUTHORS' DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST

The author(s) indicated no potential conflicts of interest.

REFERENCES

1. Khuri FR, Shin DM: Head and neck cancer chemoprevention gets a shot in the arm. J Clin Oncol 26:345-347, 2008[Free Full Text]

2. Almadori G, Bussu F, Galli J, et al: Serum folate and homocysteine levels in head and neck squamous cell carcinoma. Cancer 94:1006-1011, 2002[CrossRef][Medline]

3. Eleftheriadou A, Chalastras T, Ferekidou E, et al: Association between squamous cell carcinoma of the head and neck and serum folate and homocysteine. Anticancer Res 26:2345-2348, 2006[Medline]

4. Kraunz KS, Hsiung D, McClean MD, et al: Dietary folate is associated with p16(INK4A) methylation in head and neck squamous cell carcinoma. Int J Cancer 119:1553-1557, 2006[CrossRef][Medline]

5. Kane MA: The role of folates in squamous cell carcinoma of the head and neck. Cancer Detect Prev 29:46-53, 2005[CrossRef][Medline]

6. Sant M, Allemani C, Sieri S, et al: Salad vegetables dietary pattern protects against HER-2-positive breast cancer: A prospective Italian study. Int J Cancer 121:911-914, 2007[CrossRef][Medline]

7. Jaszewski R, Khan A, Sarkar FH, et al: Folic acid inhibition of EGFR mediated proliferation in human colon cancer cell lines. Am J Physiol 277:C1142-C1148, 1999[Medline]

8. Almadori G, Bussu F, Navarra P, et al: Pilot phase IIA study for evaluation of the efficacy of folic acid in the treatment of laryngeal leucoplakia. Cancer 107:328-336, 2006[Medline]

Related Reply

• In Reply
  Fadlo R. Khuri and Dong M. Shin
  JCO 2008 26: 3463-3464 [Full Text]

Related Article

• Head and Neck Cancer Chemoprevention Gets a Shot in the Arm
  Fadlo R. Khuri and Dong M. Shin
  JCO 2008 26: 345-347 [Full Text]

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