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[Cancer Research 61, 6708-6712, September 15, 2001]
© 2001 American Association for Cancer Research

Advances in Brief

Association between Carcinogen-DNA Adducts in White Blood Cells and Lung Cancer Risk in the Physicians Health Study1

Deliang Tang, David H. Phillips, Meir Stampfer, LaVerne A. Mooney, Yanzhi Hsu, Stan Cho, Wei-Yann Tsai, Jing Ma, Kathleen J. Cole, Meadhbh Ni Shé and Frederica P. Perera2

Division of Environmental Health Sciences, Joseph L. Mailman School of Public Health, Columbia University, New York, New York 10032 [D. T., L. A. M., Y. H., S. C., W-Y. T., F. P. P.]; Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey SM2 5NG, United Kingdom [D. H. P., K. J. C., M. N. S.]; and Channing Laboratory, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115 [M. S., J. M.]

In this matched case-control study nested within the prospective Physicians’ Health Study, we evaluated whether DNA damage in blood samples collected at enrollment significantly predicted risk, consistent with our hypothesis that cases have greater biological susceptibility to polycyclic aromatic hydrocarbons and other aromatic tobacco carcinogens. The subjects were 89 cases of primary lung cancer and 173 controls, all males, matched on smoking, age, and duration of follow-up. Aromatic-DNA adducts were measured in WBCs by the nuclease P1-enhanced 32P-postlabeling method that primarily detects smoking-related adducts. Among current smokers, but not former or nonsmokers, there was a significant increase in mean adduct levels of cases compared with controls (11.04 versus 5.63; P = 0.03). "Healthy" current smokers who had elevated levels of aromatic DNA adducts in WBCs were approximately three times more likely to be diagnosed with lung cancer 1–13 years later than current smokers with lower adduct concentrations (odds ratio, 2.98; 95% confidence interval, 1.05–8.42; P = 0.04). We were not able to discern case-control differences in former smokers and nonsmokers. The findings are of interest because they suggest that individuals who become cases have greater biological susceptibility to tobacco carcinogens, a biological difference, which manifests most clearly while exposure is ongoing.




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