Gamma-glutamyltransferase and risk of cancer in a cohort of 545,460 persons – the Swedish AMORIS study

Abstract: Background: 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. Methods: In a cohort of 545,460 persons (aged >20years) 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, ⩾72U/L) in relation to cancer risk. Stratified analyses were conducted by gender, levels of alanine aminotransferase (ALT) (</⩾50U/L), glucose (</⩾6.11mmol/L) and triglycerides (</⩾1.71mmol/L). Results: 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 ⩾6.11mmol/L, the association between GGT and risk of prostate, breast and liver cancer became stronger (e.g. HR for GGT ⩾72U/L and prostate cancer: 1.11 (0.98–1.26) and 1.35 (1.00–1.81) for glucose <6.11 and ⩾6.11mmol/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. Conclusion: 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. [Copyright &y& Elsevier]