Reduced DNA repair capacity in lung cancer patients.
Although lung cancer is the paradigm of a tobacco-induced malignancy, host-specific factors modulate susceptibility to tobacco carcinogenesis. Variations in DNA repair may influence the rate of removal of DNA damage and of fixation of mutations. To test the hypothesis that genetically determined DNA repair capacity (DRC) modulates lung cancer susceptibility, we conducted a pilot case-control study of 51 patients with newly diagnosed, previously untreated lung cancer and 56 controls identified from local community centers and frequency matched to the cases on age, sex, and ethnicity. The subjects were ascertained and interviewed for an ongoing molecular epidemiological investigation of lung cancer susceptibility. We measured DRC in the subjects' peripheral blood lymphocytes by using the host-cell reactivation assay, which measures cellular reactivation of a reporter gene damaged by exposure to 75 microM benzo(a)pyrene diol epoxide. The mean level of DRC in cases (3.3%) was significantly lower than that in controls (5.1%) (P < 0.01). Only nine cases (18%) had DNA repair levels greater than the median value of repair in the controls. This median level of DRC in controls was used as the cutoff value for calculating the odds ratios. After adjustment for age, sex, ethnicity, and smoking status, the cases were five times more likely than the controls to have reduced DRC (odds ratio, 5.7; 95% confidence interval, 2.1-15.7). Younger cases (< 65 years) and smokers were more likely than controls to have reduced DRC. These findings suggest that individuals with reduced DRC are at an increased risk of developing lung cancer.
Wei
Q
Q
Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA. qwei@request.mda.uth.tmc.edu
Cheng
L
L
Hong
W K
WK
Spitz
M R
MR
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000633:toxicity; D000367:Age Factors; D000368:Aged; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D003587:Cytomegalovirus; D004249:DNA Damage; D004260:DNA Repair; D005006:Ethnicity; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood* / Q000145:classification / Q000453:epidemiology; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity; D012016:Reference Values; D012307:Risk Factors; D012907:Smoking
D009153:Mutagens; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D015500:Chloramphenicol O-Acetyltransferase