Distribution, Determinants, and Prognostic Value of γ-Glutamyltransferase for All-Cause Mortality in a Cohort of Construction Workers from Southern Germany

Brenner, Hermann; Rothenbacher, Dietrich; Arndt, Volker; Schuberth, Stephan; Fraisse, E; Fliedner, Theodor M.

doi:10.1006/pmed.1997.0144

Cited by 75 publications

(71 citation statements)

References 19 publications

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“…The latter is supported by studies linking elevated GGT levels directly to increased risk of CVD and all-cause mortality. [1][2][3]36,37 Parallel evidence for indirect effects emerges from studies Fig. 1.…”

Section: Discussionmentioning

confidence: 63%

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels # †

et al. 2009

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The aim of the present study was to investigate the association of serum gamma-glutamyltransferase (GGT) levels with all-cause mortality and to assess the impact of ultrasonographic findings of hepatic hyperechogenicity in that association. We used data from 4,160 subjects (2,044 men and 2,116 women) recruited for the population-based Study of Health in Pomerania (SHIP) without baseline hepatitis B and C infections or liver cirrhosis. GGT was divided into age-and sex-dependent quintiles to calculate overall and sex-specific crude incidence mortality rates. Hepatic steatosis was defined by elevated GGT levels (>80%) and the presence of hyperechogenic liver ultrasound. We used multiple-adjusted Cox proportional hazards regression models, first, to assess the direct effect of GGT on all-cause mortality, second, to stratify according to the ultrasonographic finding, and third, to investigate potential mediating effects of cardiometabolic risk factors. During 29,810 person-years (7.3 years, median) of follow-up, 307 individuals (7.5%) died, resulting in a death rate of 0.86 deaths per 1000 person-years. Elevated GGT levels were associated with increased risk of mortality in men (hazard ratio [HR] 1.49; 95% confidence interval [CI], 1.08-2.05), but not in women (HR 1.30; 95% CI, 0.80-2.12). This association was even stronger in men with hepatic steatosis (HR 1.98; 95% CI, 1.21-3.27). Cause-specific mortality analysis by cardiovascular disease deaths confirmed the sex-specific association. Adjustment for cardiometabolic risk factors did not affect the estimates. Conclusion: In the case of increased GGT levels, liver ultrasound should be performed, not only for diagnosis, but also for further risk stratification.

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Section: Discussionmentioning

confidence: 63%

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels # †

et al. 2009

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“…During follow-up, 4,884 (5.3%) incident cancers were observed. On average, 3.8 GGT measurements were obtained for each participant (range [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Baseline GGT levels ranged from 3.0 to 590.7 U/L, with a median of 17.9 U/L.…”

Section: Characteristics Of Study Populationmentioning

confidence: 99%

“…17 In addition, several large-scale studies indicate an independent role of GGT for premature death from all causes. 9,18,19 The association of GGT with cancer incidence, however, remains largely unexplored. Several experimental models have elucidated the ability of cellular GGT to modulate crucial redoxsensitive functions, such as antioxidant/antitoxic defences and cellular proliferative/apoptotic balance, and its role in tumor progression, invasion and drug resistance has been proposed.…”

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confidence: 99%

Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women

Strasak

Pfeiffer

Klenk

et al. 2008

Intl Journal of Cancer

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Although several epidemiologic studies have shown that gammaglutamyltransferase (GGT) is associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In experimental models the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it may thus play a role in tumor progression. In the present study, we investigated the association of GGT with overall and site-specific cancer incidence in a population-based cohort of 92,843 Austrian women with 349,674 serial GGT measurements, prospectively followed-up for a median of 13.5 years. The relationship between GGT and cancer incidence was analyzed using adjusted Cox regression models with age as underlying time metric with age as underlying time metric including GGT concentrations at baseline and incorporating repeated GGT measurements as a time-dependent variable. During follow-up, 4,884 incidence cancers were observed. Compared to normal low GGT (<17.99 U/L), cancer risk was elevated for all other GGT categories (p for trend < 0.0001), with adjusted hazard ratios (95% confidence intervals) of 1.06 (0.99-1.13) for GGT levels between 18.00 and 35.99 U/L (normal high), 1.12 (1.02-1.22) for GGT levels between 36.00 and 71.99 U/L (elevated) and 1.43 (1.28-1.61) for highly elevated GGT (>72.00 U/L). Very similar results were seen when GGT was analyzed as a time-dependent variable. In cancer-site specific models, elevated GGT statistically significantly increased the risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and haematopoietic cancers (all, p < 0.006). Our study is the first to demonstrate in a large population-based cohort that high GGT levels significantly increased cancer risk in women.Published 2008 Wiley-Liss, Inc. This article is a US Government work, and, as such, is in the public domain in the United States of America.Key words: gamma-glutamyltransferase; cancer incidence; risk factor; epidemiology; women Gamma-glutamyltransferase (GGT), present on the external surface of most cells and in serum, is the enzyme responsible for the extracellular catabolism of glutathione (GSH), the main thiol antioxidant in mammalian cells. 1,2 In clinical practice, GGT is commonly used as a diagnostic test to assess liver dysfunction, and as a biological marker of excessive alcohol intake. 1,3,4 However, several recent epidemiologic studies have shown elevated GGT to independently influence morbidity and mortality from causes other than liver disease. Particularly, GGT was independently related to cardiovascular disease, 5-12 it correlated with most cardiovascular risk factors [13][14][15][16] and, more recently, an association with chronic kidney disease was found. 17 In addition, several large-scale studies indicate an independent role of GGT for premature death from all causes. 9,18,19 The association of GGT with cancer incidence, however, remains largely unexplored. Several ex...

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“…2 Serum levels of GGT are determined by several factors: alcohol intake, body fat content, plasma lipid/lipoproteins and glucose levels, and various medications. 1,3,4 See page 127…”

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confidence: 99%

Gamma-Glutamyl Transferase

Grundy

2007

ATVB

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Distribution, Determinants, and Prognostic Value of γ-Glutamyltransferase for All-Cause Mortality in a Cohort of Construction Workers from Southern Germany

Cited by 75 publications

References 19 publications

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels # †

Ultrasonographic hepatic steatosis increases prediction of mortality risk from elevated serum gamma-glutamyl transpeptidase levels # †

Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women

Gamma-Glutamyl Transferase

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