Cannabis smoke can be a major risk factor for early-age laryngeal cancer--a molecular signaling-based approach

Tumour Biol. 2015 Aug;36(8):6029-36. doi: 10.1007/s13277-015-3279-4. Epub 2015 Mar 4.


Epidermal growth factor receptor (EGFR) and its downstream elements are overexpressed in most cases of the head and neck squamous cell carcinoma. This study investigated the expression pattern of key proteins linked to the EGFR pathway in laryngeal carcinoma patients with a history of cannabis smoking. We selected 83 male glottic cancer patients, aged between 45 to 75 years with three distinct populations-nonsmoker, cigarette smoker, and cannabis smoker. Immunohistochemical staining was performed for EGFR, protein kinase B (PKB or Akt), nuclear factor kappa B p50 (NF-КB), and cyclooxygenase-2 (COX-2) followed by boolean scoring for statistical analysis. Experimental data showed upregulation of the selected EGFR cascade in tumor cells, stromal expression of EGFR, and nuclear localization of COX-2 in metaplastic gland cells of laryngeal cancer tissue sample. Statistical analyses indicated that overexpression of the EGFR cascade is significantly correlated to cannabis smoking. Cannabis smokers had higher expression (p < 0.01) of these onco-proteins with respect to both nonsmokers as well as cigarette smokers. Risk factor analysis showed high risk of these proteins expression in age <60 years (odds ratio (OR) > 1.5) as the lower age group had relatively higher number of cannabis smokers. This study provides evidence for a direct association between cannabis smoking and increased risk of laryngeal cancer. Higher expression of the EGFR cascade in cannabis smokers revealed that cannabis smoking may be a major cause for the early onset of aggressive laryngeal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cyclooxygenase 2 / biosynthesis*
  • Cyclooxygenase 2 / genetics
  • ErbB Receptors / biosynthesis*
  • ErbB Receptors / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Laryngeal Neoplasms / chemically induced
  • Laryngeal Neoplasms / genetics*
  • Laryngeal Neoplasms / pathology
  • Male
  • Marijuana Smoking / adverse effects
  • Middle Aged
  • NF-kappa B p50 Subunit / biosynthesis*
  • NF-kappa B p50 Subunit / genetics
  • Oncogene Protein v-akt / biosynthesis*
  • Oncogene Protein v-akt / genetics
  • Risk Factors
  • Signal Transduction / drug effects


  • NF-kappa B p50 Subunit
  • Cyclooxygenase 2
  • ErbB Receptors
  • Oncogene Protein v-akt