Miscellaneous Causes Of Oral Cancer Biology Essay

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Radiation in general can be described as a process by which energetic particles or waves travel through a medium or space. In this context, radiation mostly refers to ionizing radiation which are generally omnipresent in our surroundings such as UV light, visible light etc.. However it has been shown that radiation has a strong association with cancer epidemiologically by Ron E when she did a review along with retrospective studies conducted by Preston et al in Hiroshima and Nagasaki which was the target of the atomic bonb in World War II where 105 427 Japanese residents of these cities were observed in a retrospective cohort study between in 1958 to 1998 and found that the radiation increased the cancer rate for men at 35% and 58% for women.

With regards to oral cancer, there are many different specific causes that have been identified as mentioned below. However, it would be prudent to note that it is common in many situations that radiation along with other risk factors such as alcohol and tobacco do result in oral cancer.

i) UV radiation

UV radiation in general refers to radiation from the sunlight in the form of UV rays. It has been found that UV radiation is casually associated with skin cancers and in this respect, lip cancer, however instead of the convention squamous cell carcinoma, it was found that the lip cancer that resulted was mainly basal cancer instead.

In another study based on farmers, the findings suggest that male farmers have a significantly elevated risk for lip cancer. Lip cancer and skin cancer do not share a common etiologic factor. Besides sunlight exposure, other factors such as viral infection or reduced immunity may play a role in the etiology of lip cancer.

Odds ratio

A study done on outdoor workers employed more than 10 years which indicated that they have an higher exposure to UV radiation showed that there was an association between outdoor work and risk of non-melanoma skin cancer, cutaneous malignant melanoma and lip cancer.

'We observed an increased risk for lip cancer among men employed [10 years in an outdoor industry (OR, 1.67, 95% CI, 1.35-2.03) (Table 3). With regard to individual outdoor industries, we found a tendency for increased risks associated with construction and gardening. In the topographical analysis, men who had work[10 years outdoors had a decrease in the odds ratio of cancer on the lower lip (OR, 2.06, 95% CI, 1.70-2.50)'4

With regards to the studies on farmers, the combined RR for lip cancer was 2.0 [95% confidence interval (95% CI) 1.74-2.30] for all the studies and 1.28 (95% CI 0.79-2.08) for studies involving female farmers. Additional meta-analyses were undertaken on a subset of studies reporting on skin cancer among farmers. The combined RR for nonmelanotic skin cancer was 1.0 (95% CI 0.89-1.14), and for malignant melanoma it was 0.88 (95% CI 0.74-1.05)5

Histopathological Features:

Basal Cell carcinoma

ii) Radiation therapy

Radiation therapy is one of the most common and conventional treatment for various types of cancer which we would be describing below.

a) Radio-iodine treatment

For patients with thyroid cancer, radio-iodine treatment has been one of the most common treatment procedures in which radioactive iodine is administered to the thyroid organ of the patient. However, it was discovered in a case in which a salivary gland malignancy was presented after radioactive iodine was used as a treatment for thyroid cancer in the United States , along with many other cases that were also similarly presented in other hospitals.

However in a study conducted in 2006, while it has been acknowledged that this issue was highly controversial, there was no increased risk of a second primary malignancy that resulted from radioactive iodine treatment for thyroid cancer


According to inclusion criteria, 18,882 cases of DTC treated without RAI (mean follow-up, 55.5 months) and 10,349 cases treated with RAI (mean follow-up, 61.8 months) were identified. The most common SPM sites were breast or prostate followed by colon or lung for both groups. On univariate analysis, SPMs developed in 6.7% of patients without RAI versus 4.8% of those with RAI (p < .001, univariate chi-squared). However, on multivariate analysis, only age and male gender had statistically significant hazard ratios (1.052 and 1.438, respectively; p < .001); follicular carcinoma histology and use of RAI did not influence occurrence of SPM after DTC (p = .180 and p = .789, respectively).

*RAI: radioactive iodine

SPM: secondary primary malignancy

DTC: differentiated thyroid carcionma

However, it was also concluded that despite the lack of significance in statistics, precautions still should be taken when undergoing radio-iodine treatment due to the multitude of evidence present associating radiation with cancer.7

b) Radiation treatment for HL

Similarly for patients who are being treated for Hodgkin's lymphoma, it has been shown that HL patients treated with radiotherapy experienced a significantly increased risk of salivary gland carcinoma (SGC), particularly when exposed at young ages or for at least 2 decades after exposure. Although the results of the current study reflect the late effects of former HL treatment approaches, they point to the importance of long-term follow-up and a heightened awareness of SGC risk in this population


Among 11,047 HL patients who received radiotherapy as part of their initial treatment for HL, 21 developed subsequent invasive SGC (O/E = 16.9; 95% confidence interval [95% CI], 10.4-25.8). The risk of radiation-related SGC was highest for younger HL patients (age <20 years) (O/E = 45.5; 95% CI, 12.4-116.5) and among 10-year survivors (O/E = 23.9; 95% CI, 13.1-40.1), with risks remaining elevated for at least 2 decades after irradiation. Significant differences in risk by histologic type were observed, with a particularly high risk of developing mucoepidermoid carcinomas (O = 14; O/E = 44.2 [95% CI, 24.2-74.2]) and adenocarcinomas (O = 4; O/E = 30.6 [95% CI, 8.3-78.2]) noted.

c) Radiation treatment for Head and Neck Cancer

For patients with general head and neck cancer, radiation-induced maxillary cancers happened at a rate of 2.2% in the patients with osteoradionecrosis. There were no statistically significant differences in age, sex and the time interval between the radiotherapy and the cancer occurrence based on the study conducted in China

Radiation-induced malignancy after radiotherapy for head and neck cancer was also found to be mainly located in maxilla, presenting as squamous cell carcinoma or sarcoma of the maxillary sinus.

2) Occupational Exposure

Studies that related occupational exposure to cancer have been well documented, although occupational risk factors for the development of laryngeal cancer are well accepted, whereas the etiologic relationship between occupational exposure to various noxious influences and the development of cancer of the oral cavity and pharynx remain a matter of debate. 

Association with occupations in construction and metalworking industries, as painters, carpenters and machine operators was consistently found with oral cancer. The relative risks or standardized mortality rates ranged between 1.5 and 3. Results in regard to the textile and woodworking industry were inconclusive

Actual reasons for association are unknown although factors such as, polycyclic aromatic hydrocarbons (PAH), asbestos, welding fumes have been suggested.

Besides that, it has also been generally accepted that certain occupation actually predisposes the worker to a greater risk of oral cancer due to an increased exposure to risk factors such as tobacco and alcohol. Highly stressful jobs have also been suggested to result in a greater incidence of smoking and drinking resulting in an association with an increased risk of oral cancer

b) Occupational risk due to formaldehyde

Formaldeyhde is an organic compound which is an important precursor to many chemical compounds especially polymers. They have widespread uses in the textile, automobile, carpentry and painting industries where they are used as precursor compounds to synthesize and make various components in the associated industries.

The literature reviewed shows that occupational exposure to formaldehyde may be associated with an increased risk of nasopharyngeal and hypopharyngeal cancer, however the results regarding other occupational exposures are not consistent, therefore additional studies with more statistical power and better design are needed to ascertain if occupation is really a relevant risk factor for these types of cancer.


Formaldehyde is a direct-acting genotoxic compound that affects multiple gene expression pathways, including those involved in DNA synthesis and repair and regulation of cell proliferation.

Most studies in bacteria were positive for forward or reverse mutations without metabolic activation and for microsatellite induction.

In vitro studies with mammalian and human cells were positive for DNA adducts, DNA-protein crosslinks, DNA-DNA crosslinks, unscheduled DNA synthesis, single-strand breaks, mutations, and cytogenetic effects (chromosomal aberrations, sister chromatid exchange, and micronucleus induction. Mutations in the p53 gene were also detected in nasal squamous-cell carcinomas from rats which might result in loss-of-function mutations thus inducing malignant cell transformation

It was also found that inhalation exposure to formaldehyde also induced DNA-protein crosslinks in the nasal turbinates, nasopharynx, trachea, and bronchi of rhesus monkeys. In mice, formaldehyde exposure did not cause dominant lethal mutations, micronucleus induction, or chromosomal aberrations , when exposed by intraperitoneal injection or induce micronuclei by intravenous or oral exposure, but did induce heritable mutations when exposed by inhalation.

In studies of lymphocytes from health professional workers exposed to formaldehyde, higher levels of formaldehyde-albumin adducts were found in workers exposed to relatively high concentrations compared with workers exposed to lower concentrations and higher levels of DNA-protein crosslinks, strand breaks, and pantropic p53 protein levels were found in exposed workers compared with unexposed workers. Wang found higher levels of DNA adducts (N6-hydroxymethyldeoxyadenosine [N6 HOMe dAdo]) among smokers compared with non-smokers; however, the source of formaldehyde is not clear (for example, it could be formaldehyde in tobacco or a metabolite of a tobacco-specific compound).

Numerous studies have evaluated chromosomal aberrations and sister chromatid exchange in nasal or oral epithelial cells from humans exposed to formaldehyde (primarily health professionals, but also industrial workers, volunteers and subjects exposed from environmental sources). Among formaldehyde-exposed subjects, statistically significant increased frequencies (compared with unexposed, low exposure or pre- exposure vs. post-exposure) of cytogenetic damage in lymphocytes were observed for chromosomal aberrations in 7 of 12 reviewed studies, sister chromatid exchanges in 6 of 12 studies and micronuclei induction in 5 of 7 studies reviewed. Statistically significant increased frequencies of micronuclei were also observed in the buccal cavity or oral epithelium in four of five reviewed studies and in the nasal epithelium in all five available studies (Note that findings from two studies, Suruda et al. [1993] and Tikenko-Holland et al. [1996], evaluating the same study participants are treated as one study in this count).

Formaldehyde exposure increased expression of genes involved in intracellular adhesion, inflammation, xenobiotic metabolism, nucleic acid metabolism, cell-cycle regulation, apoptosis, and DNA repair. Thus, multiple biochemical pathways are affected by formaldehyde exposure. Mechanistic considerations: Although the biological mechanisms associated with formaldehyde-induced cancer are not completely understood, it is important to recognize that chemicals can act through multiple toxicity pathways and mechanisms to induce cancer or other health effects. Potential carcinogenic modes of actions for formaldehyde include DNA reactivity (covalent binding), gene mutation, chromosomal breakage, aneuploidy, and epigenetic effects.

Furthermore, DNA-protein crosslinks and cell-proliferation rates are correlated with the site specificity of tumors 22. Cell proliferation is stimulated by the cytotoxic effects of formaldehyde. Increased cell proliferation may contribute to carcinogenesis by increasing the probability of spontaneous or chemically induced mutations. The dose-response curves for DNA-protein crosslinks, cell proliferation, and tumor formation show similar patterns with sharp increases in slope at concentrations greater than 6 ppm. The observed sequence of nasal lesions is as follows: rhinitis, epithelial dysplasia, squamous metaplasia and hyperplasia, and squamous-cell carcinoma.

All of these studies were compiled and presented under a paper, underlining the toxicology of formaldehyde as a carcinogenic compound in the United States Department of Health.