Oral squamous cell carcinoma (OSCC) is a multifactorialdisease. The main risk factorsare lifestyle, but environment andgenetics play a variable role. Most ofthe lifestyle (modifiable) factors:
- are addictive,
- affect other body systems,
- cause other health problems,
- are often multiple habits,
- and have spread by migration.
Tobacco
All forms of tobacco, both smoked and smokeless, are carcinogenic. Tobacco generates several carcinogens (cancercausing chemicals) and for oral cancer most relevant are the tobacco-specific nitrosamines (TSNAs). These chemicals, from manufactured tobacco , as well as free radicals resulting in alterations in various antioxidant enzymes (glutathione-S-transferase, glutathione reductase, superoxide dismutase, catalase, and glutathione peroxidase), which are mutagenic.
Tobacco contains multiple carcinogens such as:
- N-nitrosamines
- NNK [4-(methylnitrosoamino)-1-(3- pyridyl)-1-butanone]
- NNN [N-nitrosonornicotine]
- PAH [Polycyclic aromatic hydrocarbons e.g. benzene and aromatic amines]
- Aromatic amines
- Heavy metals
- Tobacco contains more than 60 carcinogens.
- There is for OSCC:
- 20-fold higher risk in heavy smokers (dark tobacco is worst),
- a strong dose-response relationship.
Tobacco of course also predisposes users to:
- Cancers of the larynx, pharynx, lung, oesophagus, stomach, colon, liver, and breast,
- Other diseases (such as heart diseases and bronchitis).
Unfortunately, tobacco use is widespread worldwide and increasing in the young and in resource-poor communities.
Alcohol
Alcohol (ethanol) may be carcinogenic via various mechanisms but an important route is by its oxidization to acetaldehyde (a carcinogen) by enzymes (alcohol dehydrogenases; ADHs). Acetaldehyde is then degraded to non-carcinogenic acetate by aldehyde dehydrogenases (ALDH) (fig 1).
Genetic variations in the activities of these enzymes (ADH and ALDH) may thus influence the outcome of exposure to alcohol, and thus its carcinogenicity in any individual. There are also ethnic variations in these enzymes. High ADH activity or low ALDH lead to high acetaldehyde levels with increased carcinogenic potential- though this may be balanced if the associated ‘hangover’ headache dissuades further alcohol ?imbibition.
Acetaldehyde is also produced by:
- oral and faecal bacteria from alcohol
- smoking
- poor oral hygiene
- cytochrome P 450 2 E1
There is for OSCC a:
- 20-fold risk with heavy drinkers (spirits are the worst),
- Strong dose-response relationship.
Alcohol use also predisposes to:
- Cancers of the stomach, colon, liver, and breast
- Other diseases.
Alcohol (ethanol) use is widespread in most communities worldwide, save Islamic communities and others such as Seventh-day Adventists, but there are wide cultural and gender differences in consumption. Alcohol use is increasing in many countries, especially in the young.
Tobacco and alcohol
Tobacco and alcohol interact and contribute to a multiplicative carcinogenic effect leading to a 50- fold risk of OSCC for heavy smoking and drinking - and these lifestyle habits often co-exist of course (fig 2). Smoking increases the acetaldehyde burden following alcohol consumption and alcohol-drinking enhances the activation of pro-carcinogens present in tobacco as well as permeation through the oral epithelium.
Betel
The International Agency for Research on Cancer recently recognised that betel (which contains the stimulant arecoline) chewed as quid (with or without tobacco) is carcinogenic to humans; arecoline N-oxide is mutagenic. Betel may cause oral submucous fibrosis and cancer, and:
- Oesophageal, pancreatic, and hepatocellular cancers
- Adverse birth outcomes
- Chronic kidney disease
- Contact dermatitis
- Liver cirrhosis
- Hypertension
- Metabolic syndrome
- Betel quid (main constituent being areca nut) use is a habit of something like 20 per cent of the world’s population especially in Asian communities both in their homelands and in immigrant populations.
Khat (Qat)
Khat (Catha edulis) contains the stimulant cathinone and is commonly used especially by young males in and from South Arabia/Eastern Africa. Often tobacco is also smoked. Khat appears to be carcinogenic via free radicals and mitochondrial damage, and also may produce:
- Neurological effects
- Periodontitis
- Teratogenicity
Marijuana
The carcinogenicity of other psychotropic products such as marijuana remains controversial.
Summary
Risk factors for mouth cancer thus include:
- use of tobacco, alcohol, betel (areca) nut,
- for lip, high exposure to sunlight UV radiation.
The most important modifiable lifestyle risk factors are tobacco, alcohol and betel; these can act separately or synergistically. Heavy drinkers and tobacco smokers have almost 50 times the risk of abstainers.