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: To asses liver markers in older patients with hip fracture (HF) in relation to age, comorbidities, metabolic characteristics and short-term outcomes. In 294 patients with HF (mean age 82.0±7.9 years, 72.1% women) serum alanine aminotransferase (ALT), gammaglutamyltransferase (GGT), alkaline phosphatase (ALP), albumin, bilirubin, 25(OH)vitaminD, PTH, calcium, phosphate, magnesium, adiponectin, leptin, resistin, thyroid function and cardiac troponin I were measured. Elevated ALT, GGT, ALP or bilirubin levels on admission were observed in 1.7% - 9.9% of patients. With age GGT, ALT and leptin decrease, while PTH and adiponectin concentrations increase. Higher GGT (>30U/L, median level) was associated with coronary artery disease (CAD), diabetes mellitus (DM), and alcohol overuse; lower ALT (≤20U/L, median level) with dementia; total bilirubin >20μmol/L with CAD and alcohol overuse; and albumin >33g/L with CAD. Multivariate adjusted regression analyses revealed ALT, ALP, adiponectin, alcohol overuse and DM as independent and significant determinants of GGT (as continuous or categorical variable); GGT for each other liver marker; and PTH for adiponectin. The risk of prolonged hospital stay (>20 days) was about two times higher in patients with GGT>30U/L or adiponectin >17.14 ng/L (median level) and 4.7 times higher if both conditions coexisted. The risk of in-hospital death was 3 times higher if albumin was <33g/L. In older HF patients liver markers even within the normal range are associated with age-related disorders and outcomes. Adiponectin (but not 25(OH)vitaminD, PTH, leptin or resistin) is an independent contributor to higher GGT. Serum GGT and albumin predict prolonged hospital stay and in-hospital death, respectively. A unifying hypothesis of the findings presented.International journal of medical sciences. 01/2015; 12(2):100-15.
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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; · 2.06 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