Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons - the Swedish AMORIS study.
ABSTRACT Apart from using gamma-glutamyltransferase (GGT) as a predictor of diabetes, cardiovascular and chronic kidney disease, some evidence suggests GGT as an indicator of cancer risk. We aimed to study the association between GGT and cancer in a large Swedish cohort with 37,809 primary cancers.
In a cohort of 545,460 persons (aged >20 years) who had a measurement of GGT in the Apolipoprotein Mortality Risk (AMORIS) study, multivariate Cox proportional hazards regression was used to investigate categories of GGT (<18, 18-36,36-72, ≥72 U/L) in relation to cancer risk. Stratified analyses were conducted by gender, levels of alanine aminotransferase (ALT) (</≥ 50 U/L), glucose (</≥ 6.11 mmol/L) and triglycerides (</≥1.71 mmol/L).
A positive association was found between categories of GGT and overall cancer risk (HR: 1.07 (95%CI: 1.04-1.09,), 1.18 (1.14-1.22), 1.32 (1.26-1.38) for the 2nd, 3rd and 4th categories compared to the 1st). Stratified analyses showed that for those with glucose ≥6.11 mmol/L, the association between GGT and risk of prostate, breast and liver cancer became stronger (e.g. HR for GGT ≥72 U/L and prostate cancer: 1.11 (0.98-1.26) and 1.35 (1.00-1.81) for glucose <6.11 and ≥6.11 mmol/L, respectively). With pancreatic cancer, the association with GGT was weaker for those with elevated glucose levels compared to those with normal levels. No effects of ALT or triglyceride levels on risk were found.
We found evidence of associations between elevated GGT and risk of developing different cancers. The strength of this association may vary by glucose levels because hyperglycaemia can result in oxidative stress initiating damaging pathways of carcinogenesis.
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ABSTRACT: Background& Aims Hepatitis C virus (HCV)-infected patients with cirrhosis remain at risk of hepatocellular carcinoma (HCC) even after achieving sustained virological response (SVR). The aim of the study was to explore the incidence and risk for HCC among non-cirrhotic patients with an SVR. Methods A total of 642 patients with an SVR after peginterferon/ribavirin therapy were enrolled with a median follow-up period of 53.0 months (range: 6–133 months). Results Thirty-three of the 642 (5.1%) patients developed HCC over 2324.8 person-years of follow-up. Cox regression analysis revealed that the strongest predictive factor of HCC occurrence was liver cirrhosis (HR 4.98, 95% CI. 2.32-10.71, P<0.001), followed by age (HR 1.06, 95% CI. 1.02-1.11, P=0.005) and r-GT levels (HR 1.008, 95% CI. 1.004-1.013, P<0.001). The incidence of HCC did not differ between patients with high and low baseline r-GT levels among patients with cirrhosis (P=0.53), but the incidence of HCC was significantly higher in non-cirrhotic patients with high r-GT levels compared with those with low r-GT levels (P=0.001). Cox regression analysis revealed that the strongest factors associated with HCC development in non-cirrhotic sustained responders were baseline r-GT levels (HR 6.44, 95% CI. 2.20-18.89, P=0.001) and age (HR 3.68, 95% CI. 1.33-10.17, P=0.012). The incidence of HCC was not different between older non-cirrhotic patients with high r-GT levels and cirrhotic patients (P=0.34). Conclusions HCC remains a threat in non-cirrhotic patients with an SVR. Serum r-GT levels helped to identify potential patients at high risk.Journal of Hepatology 01/2014; · 9.86 Impact Factor
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ABSTRACT: Gamma-glutamyltransferase (GGT) is a membrane-bound enzyme involved in the glutathione metabolism. Studies suggested that GGT was a marker of apoptotic balance and modulated tumor progression, invasion and drug resistance. Recently, GGT was shown to be associated with the progression of high-grade esophageal epithelial dysplasia to invasive carcinoma. This study was conducted to investigate the value of pre-therapeutic serum GGT levels as prognostic parameter in esophageal squamous cell carcinoma. Six hundred thirty-nine resectable esophageal squamous cell carcinoma patients were recruited in this study and were stratified into two GGT risk groups. The association of pre-therapeutic serum GGT levels and clinical–pathological parameters was examined. Univariate and multivariate survival analyses were performed. GGT serum levels were associated with gender, smoking status, TNM stage and lymph node involvement. Higher pre-therapeutic serum GGT was found in males, smoker, advanced TNM stage and lymph node positive patients. Patients assigned to the low-risk group had higher 5-year overall survival rate (53.1% vs. 33.0%, P < 0.01) and disease-free survival rate (45.2% vs. 23.4%, P < 0.01) than the high-risk group. Patients with high-risk group of GGT had 1.568 (95% confidence interval [CI], 1.259 ∼ 1.952) times the risk of death and 1.582 (95% CI, 1.286 ∼ 1.946) times the risk of disease recurrence contrast with those with low-risk group of GGT. The pre-therapeutic serum GGT is a novel independent prognostic parameter for disease-free survival and overall survival in resectable esophageal squamous cell carcinoma.Diseases of the Esophagus 05/2014; · 1.64 Impact Factor
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ABSTRACT: The prospective evidence for the associations of gamma glutamyltransferase (GGT) and alanine aminotransferase (ALT) with risk of cancer in the general population is uncertain.We conducted a systematic review and meta-analysis of published prospective observational studies evaluating the associations of baseline levels of GGT and ALT with risk of overall (incidence and/or mortality) and site-specific cancers. Relevant studies were identified in a literature search of MEDLINE, EMBASE, Web of Science, reference lists of relevant studies to April 2014, and email contact with investigators. Study specific relative risks (RRs) were meta-analysed using random effects models.Fourteen cohort studies with data on 1.79 million participants and 57,534 cancer outcomes were included. Comparing top versus bottom thirds of baseline circulating GGT levels, pooled RRs (95% confidence intervals) were 1.32 (1.15-1.52) for overall cancer, 1.09 (0.95-1.24) for cancers of the breast and female genital organs, 1.09 (1.02-1.16) for cancers of male genital organs, 1.94 (1.35-2.79) for cancers of digestive organs, and 1.33 (0.94-1.89) for cancers of respiratory and intrathoracic organs. For ALT, corresponding RRs for overall cancer were 0.96 (0.94-0.99) and 1.65 (1.52-1.79) in European and Asian populations respectively. There was an increased risk of cancers of the digestive organs 2.44 (1.23-4.84). The pooled RR for overall cancer per 5 U/L increment in GGT levels was 1.04 (1.03-1.05). Available observational data indicate a positive log-linear association of GGT levels with overall cancer risk. The positive association was generally evident for site-specific cancers. There are geographical variations in the association of ALT and overall cancer. © 2014 Wiley Periodicals, Inc.International Journal of Cancer 07/2014; · 6.20 Impact Factor