Risk factors for premature death in middle aged men

Petersson, Bodil; Trell, Erik; Henningsen, N. C.; Hood, B.

doi:10.1136/bmj.288.6426.1264

Cited by 48 publications

(29 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We are aware of only two epidemiologic investigations related to the topic, both failing to detect an association between GGT and cancer mortality in middle-aged men from the general population (9,24). In a recent retrospective, hospital-based study, however, Kazemi-Shirazi et al (17) could show a significant association of GGT and cancer death in men and women.…”

Section: Introductionmentioning

confidence: 93%

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

Strasak¹,

et al. 2008

View full text Add to dashboard Cite

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 V65 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]

show abstract

Section: Introductionmentioning

confidence: 93%

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

Strasak¹,

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Others have correlated GGT with stroke, hepatobiliary diseases and premature death, using it as a marker of alcohol consumption [10][11][12].…”

Section: Introductionmentioning

confidence: 99%

Distribution and population determinants of gamma-glutamyltransferase in a random sample of Sardinian inhabitants

Pintus¹,

Mascia²

1996

Eur J Epidemiol

View full text Add to dashboard Cite

The relation of a number of determinants to serum gamma-glutamyltransferase (GGT) was studied in a random sample of Sardinian inhabitants of 2283 males and 2520 females aged 20-59 years. The aim of the study was to assess the influence of environmental, behavioural and biochemical factors on GGT levels. Mean values were higher in males than in females and increased with age in both sexes. In sex-specific multiple regression analysis, GGT showed a positive association with body mass index (BMI), alcohol use, total serum cholesterol (T-C), HDL cholesterol (HDL-C), triglycerides (TG), apolipoprotein B (ApoB) and age, and a negative one with coffee consumption and physical activity in males, while in females the enzyme was positively associated with BMI, alcohol use, age, T-C, ApoB, TG and cigarette smoking. The negative association between coffee drinking and serum GGT observed in males suggests that coffee may inhibit the inducing effects of other factors, particularly alcohol use, on GGT in the liver. No biological mechanism has been suggested to explain the association of GGT with BMI, age or physical activity. This study confirms the importance of GGT as a strong marker for alcohol use; but a number of variables, ranging from life-style to biological characteristics, are also important determinants of its plasma values in the 'normal' population.

show abstract

“…In type 2 diabetic patients, Monami and colleagues 26 recently found an association between elevated GGT and cancer-related mortality; this relationship was confirmed in a multivariate analysis after adjustment for potential confounding. However, 2 other population-based studies, 9,27 conducted in males, failed to detect an association between GGT and fatal cancer events. We thus used data from a prospective, 19-year follow-up study in Austria, to investigate the association of GGT levels and cancer incidence.…”

mentioning

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

View full text Add to dashboard Cite

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...

show abstract

Risk factors for premature death in middle aged men

Cited by 48 publications

References 22 publications

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

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

Distribution and population determinants of gamma-glutamyltransferase in a random sample of Sardinian inhabitants

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

Contact Info

Product

Resources

About