The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28 000 older Austrian women

Strasak, Alexander; Rapp, Kilian; Hilbe, Wolfgang; Oberaigner, Wilhelm; Ruttmann, Elfriede; Concin, Hans; Diem, Günter; Pfeiffer, Karl P.; Ulmer, Hanno

doi:10.1093/annonc/mdm338

Cited by 84 publications

(71 citation statements)

References 23 publications

(26 reference statements)

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“…The Vorarlberg Health Monitoring and Promotion Program (VHM&PP; refs. [25][26][27], conducted by the Agency for Social and Preventive Medicine in Vorarlberg since 1985, the westernmost province of Austria, is one of the world's largest ongoing population-based risk factor surveillance programs. All adults of the regions are invited to participate by a combination of different measures, such as written invitations, television, radio, and newspaper reports.…”

Section: Methodsmentioning

confidence: 99%

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

Strasak¹,

Rapp

Brant

et al. 2008

Cancer Research

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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]

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Section: Methodsmentioning

confidence: 99%

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

Strasak¹,

Rapp

Brant

et al. 2008

Cancer Research

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“…The Vorarlberg Health Monitoring and Promotion Program [VHM&PP] [29][30][31] is one of the world's largest ongoing populationbased risk factor surveillance programs. The cohort was initiated in 1985 and is conducted by the Agency for Social and Preventive Medicine in Vorarlberg, the westernmost province of Austria.…”

Section: Study Populationmentioning

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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“…Various mechanisms have been suggested through which uric acid may be implicated in the atherosclerotic process and its clinical complications. Uric acid can act as a prooxidant, particularly at increased concentrations, and may thus be a marker of oxidative stress (1,2 ), but it may also have a therapeutic role as an antioxidant (3,4 ). Plasma uric acid concentrations correlate with longevity in primates and other mammals (5 ), a characteristic that is presumably a function of urate's antioxidant properties.…”

mentioning

confidence: 99%

Uric Acid, Type 2 Diabetes, and Cardiovascular Diseases: Fueling the Common Soil Hypothesis?

Köenig

Meisinger

2008

Clinical Chemistry

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The role of serum uric acid as an antioxidant protecting against cancer: prospective study in more than 28 000 older Austrian women

Cited by 84 publications

References 23 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

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

Uric Acid, Type 2 Diabetes, and Cardiovascular Diseases: Fueling the Common Soil Hypothesis?

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