DNA repair related to multiple skin cancers and drug use.
Defective repair of sunlight-induced DNA photodamage, coupled with an unusually high occurrence of multiple primary basal cell carcinomas (BCCs), is the major characteristic of xeroderma pigmentosum. Our recent work has indicated that this etiological paradigm may apply to skin cancer patients without an apparent hereditary disease. The present study reports on an investigation of whether medications such as photosensitizing drugs (antibiotics, corticosteroids, and aspirin) modulate skin cancer risk through alterations in DNA repair capacity (DRC). Using a new DNA repair (host cell reactivation) assay with peripheral T-lymphocytes, we tested DRCs of 88 Caucasian BCC patients and 135 cancer-free controls. Subjects were between 20 and 60 years of age and free of known hereditary skin diseases. The age-adjusted means of DRC were calculated to compare repair levels associated with the use of specific drugs and hormones. Multiple linear regression models were used to correlate DRC with the number of skin cancers. The estimated odds ratio was used to describe the risk of BCCs. The distribution of DRCs of subjects was approximately normal, with a 5-fold variation between individuals. DRCs below the upper 30th percentile of controls were associated with an estimated 2.3-fold (95% confidence interval, 1.17-4.54-fold) increased risk for the occurrence of BCCs. The lower the DRC was, the greater the number of skin tumors in individuals (P < 0.05), after adjustment for age. Although supplemental vitamin use was associated with reduced risk of skin cancer, it was not associated with differences in subjects' DRCs. However, individuals who reported taking either tetracycline or estrogen, two photosensitizing drugs, had higher DRCs, compared with those who had not used these drugs. Low DRC or a family history of skin cancer increased the probability that patients who were overexposed to sunlight would have multiple BCCs. DNA repair levels may be influenced by the use of selected photosensitizing drugs and estrogen.
Wei, Q; Matanoski, GM; Farmer, ER; Hedayati, MA; Grossman, L
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