Repair of UV Light-Induced DNA Damage and Risk of Cutaneous Malignant Melanoma

• Published in: JNCI : Journal of the National Cancer Institute Vol. 95; no. 4; pp. 308 - 315
• Main Authors: Wei, Qingyi, Lee, Jeffrey E., Gershenwald, Jeffrey E., Ross, Merrick I., Mansfield, Paul F., Strom, Sara S., Wang, Li-E, Guo, Zhaozheng, Qiao, Yawei, Amos, Christopher I., Spitz, Margaret R., Duvic, Madeleine
• Format: Journal Article
• Language: English
• Published: Cary, NC Oxford University Press 19.02.2003; Oxford Publishing Limited (England)
• Subjects: Adult; Aged; Biological and medical sciences; Case-Control Studies; Clinical trials; Deoxyribonucleic acid; Dermatology; DNA; DNA Damage; DNA Repair; Female; Genetic Predisposition to Disease; Health risk assessment; Humans; Logistic Models; Male; Medical sciences; Melanoma - etiology; Melanoma - genetics; Middle Aged; Odds Ratio; Risk Assessment; Risk Factors; Skin cancer; Skin Neoplasms - etiology; Skin Neoplasms - genetics; Sunlight - adverse effects; Tumors of the skin and soft tissue. Premalignant lesions; Ultraviolet radiation; Ultraviolet Rays - adverse effects; United States; North America; America; Human; Skin disease; Melanoma; Malignant tumor; Case control study; Epidemiology; Electromagnetic wave; Ultraviolet radiation; DNA; Risk factor; Genetics; Skin; Lesion; Solar radiation; Repair; Public health
• ISSN: 0027-8874; 1460-2105
• DOI: 10.1093/jnci/95.4.308

Background: The mechanism underlying the role of UV light exposure from sunlight in the etiology of cutaneous malignant melanoma (CMM) is unclear. Patients with xeroderma pigmentosum, a disease characterized by severe sensitivity to UV radiation and a defect in nucleotide excision repair, have a high incidence of CMM, which suggests that DNA repair capacity (DRC) plays a role in sunlight-induced CMM in the general population as well. Methods: We conducted a hospital-based case–control study of DRC and CMM among 312 non-Hispanic white CMM patients who had no prior chemotherapy or radiation therapy, and 324 cancer-free control subjects who were frequency-matched to case patients on age, sex, and ethnicity. Information on demographic variables, risk factors, and tumor characteristics was obtained from questionnaires and medical records. We used the host-cell reactivation assay to measure the DRC in study subjects‘ lymphocytes. All statistical tests were two sided. Results: Case patients had a 19% lower mean (± standard deviation [SD]) DRC (8.5 ± 3.4%) than control subjects (10.5 ± 5.1%), a statistically significant difference (P<.001). DRC that was at or below the median value (i.e., 9.4%) in control subjects was associated with increased risk for CMM after adjustment for age, sex, and other covariates (odds ratio [OR] = 2.02, 95% confidence interval [CI] = 1.45 to 2.82). We observed a dose–response relationship between decreased DRC and increased risk of CMM (Ptrend<.001). Patients with tumors on sun-exposed skin had statistically significantly lower DRC than patients with tumors on unexposed skin (8.2 ± 3.3% versus 9.5 ± 3.5%; P = .004). Conclusions: Reduced DRC is an independent risk factor for CMM and may contribute to susceptibility to sunlight-induced CMM among the general population.