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Association of -Glutamyltransferase and Risk of Cancer Incidence in Men: A Prospective Study

Departments of ¹ Medical Statistics, Informatics and Health Economics, ² Haematology and Oncology, and ³ Cardiac Surgery, Innsbruck Medical University; ⁴ Cancer Registry of Tyrol, Department of Clinical Epidemiology of the Tyrolean State Hospitals Ltd., Innsbruck, Austria; ⁵ Department of Epidemiology, University of Ulm, Ulm, Germany; ⁶ Gerontology Research Center, National Institute on Aging, Baltimore, Maryland; ⁷ SAS Institute, Inc., Heidelberg, Germany; and ⁸ Agency for Preventive and Social Medicine, Bregenz, Austria

Requests for reprints: Alexander M. Strasak, Department of Medical Statistics, Informatics and Health Economics, Innsbruck Medical University, Schoepfstrasse 41, 6020 Innsbruck, Austria. Phone: 43-512-9003-70921; Fax: 43-512-9003-73922; E-mail: alexander.strasak{at}i-med.ac.at.

Key Words: -glutamyltransferase • cancer incidence • risk factor • epidemiology • men

Although several epidemiologic studies have shown that -glutamyltransferase (GGT) is independently associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In several experimental models, the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it thus may play a role in tumor progression, as has been repeatedly suggested. We prospectively investigated the association between GGT and risk of overall and site-specific cancer incidence in a large population-based cohort of 79,279 healthy Austrian men with serial GGT measurements. Median follow-up was 12.5 years. Adjusted Cox proportional hazards models were calculated to evaluate GGT as an independent predictor for cancer incidence, and nonparametric regression splines were fitted to flexibly capture the dose-response relationship. Elevated GGT significantly increased overall cancer risk, showing a clear dose-response relationship (P for GGT log-unit increase < 0.0001; P for trend < 0.0001). In comparison with the reference GGT concentration (25 units/L), we found adjusted relative risks (95% confidence intervals) equalling 1.19 (1.15-1.22) for GGT concentrations of 60 units/L, 1.32 (1.28-1.36) for 100 units/L, 1.67 (1.60-1.75) for 200 units/L, and 2.30 (2.14-2.47) for 400 units/L. In cancer site-specific models, GGT was significantly associated with malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, and urinary organs (all P < 0.0001). Age of participants significantly modified the association of GGT and cancer risk (P < 0.001), revealing markedly stronger associations in participants ages 65 years. Our findings, for the first time, show that elevated GGT is significantly associated with increased cancer risk in men. [Cancer Res 2008;68(10):3970–7]