Sandbox SSW

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sargun Singh Walia M.B.B.S.[2]

Overview

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3]; Associate Editor(s)-in-Chief:

Pathophysiology of Oral Cancer

Tumor suppressor genes (TSGs)

• It is understood that oral cavity cancer is the result of allelic imbalance which is caused by chromosomal changes particularly in chromosome 3,9,11 and 17.
• These changes lead to mutation in tumor suppressor genes (TSGs).
• Normally TSGs modulate normal growth.
• Mutation of these TSGs leads to dysfunctional growth control.
• Mutation most commonly occurs in either of the following:
  • Short arm of chromosome 3
  • TSG termed P16 on chromosome 9
  • TSG termed TP53 on chromosome 17
• Cytochrome P450 genotypes is related to mutations in some TSGs and lead to oral squamous cell carcinoma.
• In western countries (eg, United Kingdom, United States, Australia) TP53 mutations are the most common molecular change that leads to oral squamous cell carcinoma.

Oncogenes

• Cancer may also occur if there is mutation to other genes that control cell growth, mainly oncogenes.
• Oncogenes most commonly involved are:
  • Chromosome 11 (PRAD1)
  • Chromosome 17 (Harvey ras [H-ras])
• In eastern countries (eg, India, Southeast Asia), ras oncogenes is a more common cause of oral squamous cell carcinoma.

Carcinogen-metabolizing enzymes

• Carcinogen-metabolizing enzymes are known to cause cancer in some patients.
• Cytotoxic enzymes such as alcohol dehydrogenase result in the production of:
  • Free radicles
  • DNA hydroxylated bases
• These cytotoxic enzymes especially predispose oral squamous cell carcinoma.

Alcohol

• Alcohol dehydrogenase oxidizes ethanol to acetaldehyde which is cytotoxic in nature.
• cytochrome P450 IIEI (CYP2E1) also metabolizes ethanol to acetaldehyde.
• Alcohol dehydrogenase type 3 genotype predisposes to oral squamous cell carcinoma.
• Carcinogenic potential increases when combined with tobacco use.

Tobacco

• Cigarette smoke has various carcinogens which can lead to oral cancers.
• Low reactive free radicals in cigarette smoke interact with redox-active metals in saliva.
• This makes saliva to loose its antioxidant potential and become a potent pro-oxidant milieu.

Gross Pathological Findings

Images shown below are courtesy of Professor Peter Anderson DVM PhD and published with permission. © PEIR, University of Alabama at Birmingham, Department of Pathology

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