Biomarkers for Oral Cancer

The purpose is to determine the extent of genetic damage in oral mucosal lesions ascertained
in the study, whether specific genotypes are associated with genetic damage observed in the
oral mucosal lesions, whether the extent of genetic damage changes over time, and what
factors (e.g. smoking) contribute to those changes. Genetic damage indicators will include
among others DNA adduct formation, particularly related to tobacco smoke carcinogens such as
polycyclic aromatic hydocarbons. The genotypes of interest will be focused on these affecting
carcinogen metabolism, (e.g., (CYP family), but may also include those related to growth
factors, cell cycle control, and DNA repair. Microsatellite instability is another key
indicator of damage that we plan to examine. This study was undertaken due to the paucity of
data on the types of oral lesions seen in general dental practice and the limited knowledge
of the natural history of these lesions.

Persons were enrolled who had red and/or white oral lesions identified at 6 Dental Clinics at
VA Medical Centers. The VA Centers involved were: Washington, DC; Atlanta, GA; Durham, NC;
San Francisco, CA; Danville, IL; and San Antonio, TX.

When a dentist found a red or white lesions in the course of routine outpatient examinations
and care, obvious causes such as denture frictional lesions could be ruled out, and the
normal standard of care for the lesion was biopsy, the patient was considered for enrollment
into the study. The study was described to the patient, the consent for was signed, the
patient received an intraoral examination to identify and characterize the oral lesions, the
lesions were photographed, an oral epithelial cell sample was taken from the site and from
the rest of the oral mucosa, and the patient was interviewed using a standard questionnaire
that requested information about sociodemograhic, medical, and lifestyle factors,
particularly tobacco and alcohol use all as part of the study protocol, and the patient
received a biopsy as part of normal care. The biopsy report was obtained as was a small piece
of the biopsy material that was not needed for patient diagnostic purposes. The subjects
returned every 4-6 months for reassessment of the lesion or to determine that the lesion had
not returned. The patients completed a questionnaire at each of these visits so that
lifestyle factors such as tobacco and alcohol use could be reassessed. Also oral epithelial
cell scrapings were obtained at each of these visits.

This study is particularly valuable because longitudinal data was collected and because the
data were collected over time using standard procedures.