Association of γ-Glutamyltransferase and Risk of Cancer Incidence in Men: A Prospective Study
- 15 May 2008
- journal article
- Published by American Association for Cancer Research (AACR) in Cancer Research
- Vol. 68 (10), 3970-3977
- https://doi.org/10.1158/0008-5472.can-07-6686
Abstract
Although several epidemiologic studies have shown that γ-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]Other Versions
This publication has 42 references indexed in Scilit:
- The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28 000 older Austrian womenAnnals of Oncology, 2007
- Serum uric acid and risk of cancer mortality in a large prospective male cohortCancer Causes & Control, 2007
- γ-Glutamyltransferase as a Predictor of Chronic Kidney Disease in Nonhypertensive and Nondiabetic Korean MenClinical Chemistry, 2007
- Modulation of cell growth and cisplatin sensitivity by membrane γ-glutamyltransferase in melanoma cellsEuropean Journal of Cancer, 2006
- Association between Serum Concentrations of Persistent Organic Pollutants and γ Glutamyltransferase: Results from the National Health and Examination Survey 1999–2002Clinical Chemistry, 2006
- Serum gamma-glutamyltransferase predicts non-fatal myocardial infarction and fatal coronary heart disease among 28 838 middle-aged men and womenEuropean Heart Journal, 2006
- Graded Associations of Blood Lead and Urinary Cadmium Concentrations with Oxidative-Stress–Related Markers in the U.S. Population: Results from the Third National Health and Nutrition Examination SurveyEnvironmental Health Perspectives, 2006
- Estimating dose‐response relationship between ethanol and risk of cancer using regression spline modelsInternational Journal of Cancer, 2005
- Storage of Serum or Whole Blood Samples? Effects of Time and Temperature on 22 Serum Analytescclm, 1995
- Risk factors for premature death in middle aged menBMJ, 1984