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

Abstract

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...

Study of Serum Lactate Dehydrogenase and Gamma-Glutamyl Transpeptidase in Breast Cancer Patients receiving Chemotherapy

“…GGT is crucially involved in cell's detoxification pathway and apoptotic balance-including tumor development, progression and chemotherapy resistance [9,10]. An elevated GGT level significantly increased the risk of developing neoplasms of breast, female genital organs, digestive organs, lymphoid and hematopoietic cancers [20]. Similarly, Grimm et al [9] reported elevated serum GGT level is associated with increased cancer risk and worse prognosis of gynecologic cancers.…”

Pooling-Based Genome-Wide Association Study Implicates Gamma-Glutamyltransferase 1 (GGT1) Gene in Pancreatic Carcinogenesis

“…However, elevated GGT levels have also been found associated with various other diseases, including cardiovascular disease, and serum GGT has been proposed as a marker of oxidative stress [24]. Importantly, Strasak et al [25,26] recently reported that elevated GGT serum levels were significantly associated with increased cancer risk in men and women in a large population-based cohort. Associations between serum GGT levels and risk of pancreatic cancer specifically have, to our knowledge, not yet been investigated.…”

Serum gamma-glutamyltransferase level is associated with serum superoxide dismutase activity and metabolic syndrome in a Japanese population

“…GGT has attracted considerable attention as a predictor of metabolic syndrome, insulin resistance, cardiovascular disease, stroke, and cancer [2][3][4][5][6][7]. Furthermore, elevated GGT is associated with higher allcause mortality [8,9].…”