Genetic Considerations of Diseases and Disorders that Affect the Oral

Cavity
Part II. Oral Cancer and Developmental Disorders
S. Michele Robichaux, D.D.S.
CANCER OF THE ORAL CAVITY
Cancers involve body tissues whose cells are dividing and growing faster than cells are
dying. The result of excessive cell growth is an enlarged mass called a tumor. Cancers
may fail to remain within the boundaries of normal tissues and therefore spread or
invade surrounding healthy tissues. Unfortunately, cancer of the head and neck is
diagnosed relatively frequently. The most common oral cancers involve the surface
tissue (epithelium) of the mouth and pharynx.
RISKS FACTORS FOR DEVELOPING ORAL CANCER
Genetic Factors. Genetic factors involved in the development of cancer include:

Hereditary predisposition. An individual with a hereditary predisposition for cancer is

a person with an increased likelihood of developing cancer due to inherited genes.
These inherited genes make body cells more sensitive to environmental factors, such as
sunlight and tobacco, and, therefore change normal body cells into cancer cells.

Oncogenes. Cancers can be derived from mutations in genes that

change cell growth patterns. These genes are called oncogenes. Such a
mutation in an oncogene can convert ordinary body cells into cancer
cells. Cancers caused by oncogenes are not inherited. To date, scientists
have discovered more than 100 oncogenes, and several oncogenes have
been associated with cancers of the head and neck.
Tumor suppressor genes. Normal tumor suppressor genes are anticancer genes that slow down or stop growth of normal body cells.
Mutations of tumor suppressor genes can also cause the development of
oral and pharyngeal cancers.

Tobacco and Alcohol. Use of tobacco and alcohol are the

major risk factors for developing oral cancer. Tobacco and
alcohol contains substances that are carcinogenic or
promote cancer. Cigarettes smoke and substances in
smokeless tobacco have received considerable attention as
carcinogens that promote oral cancer. Studies also indicate
that smoking in combination with consumption of alcohol
produces an even greater risk for oral cancer than use of
either substance alone.
Radiation. Radiation of high dosage and prolonged

duration can produce cancer. There is no evidence that routine dental X-rays are
carcinogenic, especially with today's high speed, low dosage machines.
Traumatic irritation. Prolonged irritation from broken teeth, rough dental restorations,
and ill-fitting dentures are considered a possible causes for oral cancer.
Viruses. Some viruses can cause cancer in human cells. Studies have indicated a link
to oral cancer with infections from herpes simplex type- I virus, Epstein-Barr virus, and
human papillomavirus.
DIAGNOSIS AND EVALUATION
Early diagnosis is the single factor in successfully combating oral cancer. Therefore, it is
crucial that the patient seeks immediate and proper treatment for the disease. If tissue of
the mouth is suspected to be cancerous, a biopsy is necessary. A biopsy involves
surgically removing diseased tissue for microscopic evaluation and diagnosis by a
pathologist.
PRE-CANCEROUS LESIONS OF THE MOUTH
Pre-cancerous refers to early changes of normal cells that are changing into cancer
cells. Recognition of pre-cancerous tissue of the mouth is an important role in the
diagnosis and prevention of oral cancer by the dental health professional. Many times,
pre-cancerous tissue goes unnoticed by an individual because it is not painful. As a
general rule, pre-cancerous or early cancers do not heal.
Leukoplakia. Leukoplakia is a term that describes a 'white patch' on the surface of oral
tissues. Leukoplakias have been associated with pre-cancerous tissues. In general,
leukoplakias are suspected as pre- or early cancer if the white area cannot be scraped
off the surface tissue and cannot be attributed to another disease.
Erythroplakia. Erythroplakia occurs in the oral cavity as a distinct and well-defined
patch with a bright red and velvety surface. Erythroplakias are relatively rare lesions of
the oral cavity. Erythroplakias are almost always pre-cancerous.
DESCRIPTION OF SELECTED ORAL CANCERS
Cancers can involve growth changes to any tissue of the oral cavity. Cancers of the
mouth may be benign or malignant tumors. A benign tumor is a mass limited within a
connective tissue capsule. This type of tumor does not spread or invade adjacent tissue
and is therefore usually not life-threatening. A malignant tumor, on the other hand, is a
mass capable of spreading and invading other healthy tissues of the body. The spread of
cancer cells occurs by traveling within the bloodstream or lymph system. A malignant
tumor can then form additional sites of cancers away from the original tumor, a process
called metastasis. Malignant tumors are dangerous and difficult to control. Welldeveloped malignant cancers can be life threatening.
Squamous Cell Carcinoma. Squamous cell carcinoma is
the most frequently occurring malignant cancer of the oral
region. This type of cancer involves cell growth changes of
the surface tissue of the oral region, the epithelium. Nearly
90% of all oral cancers are squamous cell carcinomas. The
most frequent location of this cancer is on the lips, the
tongue, and the floor of the mouth. A chronic (long-term)
mouth ulcer that does not heal, a lesion attached to deeper
tissues, and a red-velvety lesion are all suspect squamous
cell carcinomas. If left untreated, squamous cell carcinomas
undergo metastasis and involve vital organs of the body.
Many times death is the result of complications to the heart and lungs.
Basal Cell Carcinoma. Basal cell carcinoma is a tumor located on the surface of skin

that has hair. Basal cell carcinomas are associated with prolonged exposure of skin to
the sun. Lesions initially appear as elevated blisters, followed by a period of ulceration
and healing. Continued cycles of blistering, ulcerating, and healing of the same tissue
occurs as deeper tissues are slowly invaded. Metastasis of basal cell carcinomas is rare,
and survival rate of individuals diagnosed with basal cell carcinoma is excellent.
Fibromas. Fibromas are benign tumors whose cell origin lies in the connective tissue
supporting teeth within tooth sockets, the periodontal membrane.
Osteomas. Osteomas are benign tumors whose cell origin is the bone of the upper and
lower jaw.
Malignant tumors of connective tissue origin. Malignant tumors of connective tissue
origin (the periodontal membrane, bone and cartilage) include fibrosarcomas,
osteosarcomas and chondrosarcomas.
Tumors of the teeth. Tumors involving cells of the teeth are termed odontogenic
tumors.
Salivary gland tumors. Salivary gland tumors are varied in their degree of malignancy
and tumor cell origin. Salivary gland tumors can be benign or malignant. This type of
tumor is very rare.
TREATMENT OF ORAL CANCER
The three major treatment considerations for oral cancer include:
1.

2.

3.

Surgical removal of diseased tissue. This is the best management for

treatment of cancer if possible. The advantages for surgery are prompt
treatment and the ability of physicians to study tissue removed during surgery
with a microscope. With this study, it can be known that the entire tumor has
been removed. The disadvantage of surgical treatment is normal tissue loss in
the attempt to remove all diseased tissue. Another consequence to surgery is
the risk of loss of function and cosmetic defects.
Radiation therapy. This is an effective form of treatment for isolated areas of
cancer. As the size of the tumors enlarge, larger doses of radiation are
necessary to kill cancer cells. The advantages of radiation therapy are the
preservation of normal tissues and the maintenance of normal tissue function.
The major disadvantage of radiation therapy includes inflammation of the lining
of the mouth, destruction of salivary gland tissue that can result in dry mouth,
changes in taste sensations, dental decay, damage to small blood vessels, and
the risk of necrosis to bone tissue.
Chemotherapy. Chemotherapy is dependent on the cancer diagnosis. Therapy
can be designed for a systemic approach (one that treats the entire body) or a
regional approach (one that treats the only the area of the cancer). The
appropriate medication and duration of treatment is determined by evaluating
the location of the cancer and the severity of the disease process. There are
many side effects to chemotherapy, including
complications affecting cells of the bone marrow,
the gut, and lining of the mouth.
Treatment of most cancers of the head and neck involve a
combination of surgery, radiation and chemotherapy.
DEVELOPMENTAL DISORDERS OF THE HEAD
Developmental disorders of the head (craniofacial region)
are the result of problems that occur during development
and growth of a baby prior to birth. Genes responsible for
formation of the head very early in pregnancy

(approximately three weeks following conception) are also responsible for the
development of limbs and vital organs, such as the heart and lungs. Therefore,
craniofacial defects are many times components of other developmental defects. Many
studies conclude that developmental defects result from the interaction of multiple genes
and environmental factors.
DESCRIPTION OF SELECTED DEVELOPMENTAL DEFECTS
Cleft Lip and Cleft Palate. The most common of all craniofacial defects is the cleft lip
and cleft palate. Clefting, or incomplete fusion of the lip and/or palate, can occur alone or
as part of a hereditary syndrome. The pattern of inheritance in cleft lip and cleft palate
suggests that up to twenty genes are involved with this defect.
Craniosynostoses. Craniosynostoses is a genetic disorder that causes early fusion of
the bones surrounding and protecting the brain (bones of the skull). As a result,
dangerous amounts of pressure are created against an enlarging brain within a
braincase that is not growing. Several hereditary syndromes include mental retardation
due to craniosynostoses as a characteristic feature.
Hereditary Anodontia. Conditions of the complete absence of teeth (anodontia) have
been correlated to specific genes. The complete absence of teeth alters bone
development within the upper and lower jaws of the mouth.
Amelogenesis Imperfecta and Dentinogenesis Imperfecta. Amelogenesis imperfecta
is a genetic disorder that results in defective enamel formation of teeth. Enamel is the
hard surface covering the crowns of teeth. Amelogenesis imperfecta either causes
problems in enamel hardening (mineralization) of normal amounts of enamel or causes a
smaller amount of normal enamel to be produced. Dentinogenesis imperfecta is a
genetic disorder that results in defective dentin formation within teeth. Dentin is a
mineralized material forming the bulk of each tooth. Defective dentin causes the normal
enamel layer that covers the tooth to flake off. In both diseases, the teeth are weak and
very sensitive to temperature and pressures. Amelogenesis imperfecta and
dentinogenesis imperfecta are linked to defects in structural genes that code for proteins
necessary for the development of enamel and dentin.
Osteogenesis Imperfecta. Osteogenesis imperfecta is an inherited disease caused by
mutations of genes that produce collagen. Collagen is an important substance within
connective tissues of the body such as bone. Osteogenesis imperfecta causes 'brittle
bone' diseases that affect all bones of the body. A complication of osteogenesis
imperfecta that involves tissues of the mouth in addition to the more generalized effect of
fragile bones is a painful dentinogenesis imperfecta-like change in the teeth.
REFERENCES
Blot, W.J., J.K. McLaughlin, D.M. Winn, D.F. Austin, R.S. Greenberg, S. Preston-Martin,
L. Bernstein, J.B. Schoenberg, A. Stemhagen, and J.F. Fraumeni. 1988. Smoking and
drinking in relation to oral and pharyngeal cancer. Cancer Research 48:3282-3287.
Bricker, S.L., R.P. Langlais and C.S. Miller. 1994. Oral Diagnosis, Oral Medicine, and
Treatment Planning, Second Edition. Philadelphia, Lea and Febiger Publishing.
Greenblatt, M.S., W.P. Bennett, M. Hollstein, C.C. Harris. 1994. Mutations in the p53
tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer
Research 54(18):4855-4878.
Lidral, A.C., J.C. Murray, K.H. Buetow, A.M. Basart, H. Schearer, R. Schiang, A. Naval,
E. Layda, K. Magee, W. Magee. 1997. Studies of the candidate genes TGFB2, MSX1,
TGFA, and TGFB3 in the etiology of cleft lip and palate in the Philippines. Cleft Palate -

Craniofacial Journal 34(1):1-6.

Shklar G. 1986. Oral Leukoplakia. New England Journal of Medicine 315(24):1544-1546.
Spandidos D.A. A. Lamothe, J.K. Field. 1985. Multiple transcriptional activation of
cellular oncogenes in human head and neck solid tumors. Anticancer Research
5(2):221-224.
U.S. Department of Health and Human Services. 2000. Oral Health in America: A Report
of the Surgeon General. U.S. Public Health Service.
HOW TO LEARN MORE
www.ADA.org This is the American Dental Association website, which provides access
to news and publications related to dental health
www.aaoms.org This is the American Association of Oral and Maxillofacial Surgeon
website, which contains information about oral and maxillofacial surgery including oral
cancer.
www.tonguecancer.com This site provides diagnosis and treatment for cancers of the
head and neck.
www.clapa.cwc.net This is the Cleft Lip and Palate Association website, which provides
information and support to anyone with or affected by cleft lip and clept palate
www.cleftline.org This is the American Cleft Palate-Craniofacial Association website.
This national organization provides lay and professional services for cleft lip, cleft palate,
and other craniofacial defects.
ABOUT THE AUTHOR
S. Michele Robichaux, D.D.S, is an associate professor of biology at Nicholls State
University in Thibodaux, Louisiana. She teaches Human Anatomy, Physiology and
Histology. Her research interests include the genetics and microbiology of periodontal
disease.
CONTACT THE AUTHOR
Dr. S. Michele Robichaux
Department of Biological Sciences
Nicholls State University
Thibodaux, LA 70310
(985) 448-4721
biol-smr@nicholls.edu

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