DNA repair capacity for ultraviolet light-induced damage is reduced in peripheral lymphocytes from patients with basal cell carcinoma.
Sunlight exposure and certain host factors such as red hair and fair skin are established risk factors for non-melanoma skin cancers. Because deficient DNA repair capacity has contributed to the development of skin cancers in a rare genetic disease, xeroderma pigmentosum, we explored this deficiency as an etiologic factor in a recent population study. We used a new DNA repair assay, the host-cell reactivation, in a clinic-based case-control study to test the hypothesis that reduced DNA repair is the underlying molecular mechanism for the development of sunlight-induced basal cell carcinoma. The peripheral lymphocytes from 88 patients with primary BCC and 135 cancer-free controls were tested for their capacity to repair ultraviolet light-induced DNA damage in a reporter gene, chloramphenicol acetyl transferase. All subjects were between the ages of 20 and 60 years and were frequency matched by age (+/- 5) and sex. Among those who reported frequent sunbathing, poor tanning ability, a history of multiple sunburns, exposure to chemicals, or multiple medical irradiations, the BCC patients had significantly lower DNA repair capacity than controls (p < 0.05). DNA repair capacity was also found substantially lower in the basal cell carcinoma patients who had red hair and light skin (type I). Compared to controls, basal cell carcinoma cases with selected risk factors had a relative decrease in DNA repair capacity of 10-28%. These findings provided evidence that reduced DNA repair capacity is one of the underlying molecular mechanisms for sunlight-induced skin carcinogenesis in the general population.
Wei
Q
Q
Department of Epidemiology, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA.
Matanoski
G M
GM
Farmer
E R
ER
Hedayati
M A
MA
Grossman
L
L
D000328:Adult; D002273:Carcinogens / Q000494:pharmacology; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D006801:Humans; D008214:Lymphocytes / Q000528:radiation effects*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology*; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays
D002273:Carcinogens