title: Repair of UV light-induced DNA damage and risk of cutaneous malignant melanoma.
abstract: 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 (P(trend)<.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.
authors.affiliation: Department of Epidemiology, Unit 189, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. qwei@mdanderson.org
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Lee
authors.forename: Jeffrey E
authors.initials: JE
authors.lastname: Gershenwald
authors.forename: Merrick I
authors.initials: MI
authors.lastname: Ross
authors.forename: Paul F
authors.initials: PF
authors.lastname: Mansfield
authors.forename: Sara S
authors.initials: SS
authors.lastname: Strom
authors.forename: Li-E
authors.initials: LE
authors.lastname: Wang
authors.forename: Zhaozheng
authors.initials: Z
authors.lastname: Guo
authors.forename: Yawei
authors.initials: Y
authors.lastname: Qiao
authors.forename: Christopher I
authors.initials: CI
authors.lastname: Amos
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Spitz
authors.forename: Madeleine
authors.initials: M
authors.lastname: Duvic
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D004249:DNA Damage; D004260:DNA Repair; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016015:Logistic Models; D008297:Male; D008545:Melanoma / Q000209:etiology* / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics; D013472:Sunlight / Q000009:adverse effects; D014466:Ultraviolet Rays / Q000009:adverse effects*