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.
- SourceAvailable from: Toshinao Goda[Show abstract] [Hide abstract]
ABSTRACT: We previously demonstrated that the circulating concentrations of interleukin (IL)-1β, which is known to induce the development and progression of type 2 diabetes and its complications, were positively associated with γ-glutamyltransferase (γ-GTP) activity in middle-aged apparently healthy Japanese men. It was still unknown if the association between IL-1β concentrations and γ-GTP activity is within the normal range in apparently healthy Japanese women. In this study, we conducted a cross-sectional study of 824 apparently healthy women aged 40-64 y [mean±standard deviation age, 53.1±7.1 y; body mass index (BMI), 22.0±3.1 kg/m(2)] who participated in health checkups in Japan, and whose γ-GTP activity was within the normal range (<38 U/L). Associations of γ-GTP with IL-1β and other clinical or lifestyle factors were determined using analysis of variance (ANOVA) and one-way analysis of covariance (ANCOVA) followed by Tukey's multiple-range test. Multivariate logistic regression analyses (MLRA) were performed with γ-GTP activity as the dependent variable; independent variables included IL-1β plus clinical and lifestyle factors. ANOVA and ANCOVA indicated that IL-1β concentrations were positively associated with γ-GTP activity. MLRA showed that γ-GTP activity showed trends for higher IL-1β concentrations after adjusting for age, BMI, energy intake, alcohol intake, and smoking status. Together, IL-1β concentrations are positively associated with γ-GTP activity within the normal range in middle-aged apparently healthy Japanese women. Our results suggest that γ-GTP activity would be useful for assessing inflammation from the healthy state in Japanese women.Journal of Nutritional Science and Vitaminology 01/2013; 59(6):526-32. DOI:10.3177/jnsv.59.526 · 0.87 Impact Factor
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ABSTRACT: The cystathionine beta synthase (CBS) gene plays an important role in homocysteine metabolism because it catalyzes the first step of the transsulfuration pathway, during which homocysteine is converted to cystathionine. Polymorphisms of CBS have been associated with cancer. We examined the role of the 844ins68 polymorphism by comparing the genotypes of 371 healthy Mexican women with the genotypes of 323 Mexican women with breast cancer (BC). The observed genotype frequencies for controls and BC patients were 1% and 2% for Ins/Ins, 13% and 26% for W/Ins, and 86% and 72% for W/W, respectively. We found that the odds ratio (OR) was 2.2, with a 95% confidence interval (95% CI) of 1.5-3.3, p = 0.0001. The association was also evident when comparing the distribution of the W/Ins-Ins/Ins genotypes in patients in the following categories: 1) menopause and high γ-glutamyltransferase (GGT) levels (OR of 2.17, 95% CI: 1.17-4.26, p = 0.02), 2) chemotherapy response and high lactate dehydrogenase (LDH) levels (OR 2.2, 95% CI: 1.08-4.4, p = 0.027), 3) chemotherapy response and high GGT levels (OR 2.46, 95% CI: 1.2-4.8, p = 0.007), and 4) body mass index (BMI) and III-IV tumor stage (OR 3.2, 95% CI: 1.2-8.3, p = 0.013). We conclude that the genotypes W/Ins-Ins/Ins of the 844ins68 polymorphism in the CBS gene contribute significantly to BC susceptibility in the analyzed sample from the Mexican population.Archives of Medical Science 12/2014; 10(6):1214-24. DOI:10.5114/aoms.2014.47830 · 1.89 Impact Factor
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ABSTRACT: Background:Gamma-glutamyltransferase (GGT) - a membrane-bound enzyme crucially involved in the cell's detoxification pathway and apoptotic balance - is involved in tumour development, progression and chemotherapy resistance. Elevated GGT serum levels are associated with increased cancer risk in women and worse prognosis in gynaecologic cancers. The present study investigated the prognostic role of GGT in ovarian cancer patients.Methods:In this multicenter study, pre-therapeutic GGT levels were ascertained in 634 consecutive patients with epithelial ovarian cancer (EOC, n=567) and borderline tumour of the ovary (BTO, n=67). Gamma-glutamyltransferase serum levels were associated with clinicopathological parameters and uni- and multivariate survival analyses were performed. Immunohistochemistry of GGT was performed in ovarian cancer tissue and correlated with GGT serum levels.Results:Pre-therapeutic GGT serum levels were higher in patients with EOC (28.56 (38.24) U l(-1)) than in patients with BTO (20.01 (12.78) U l(-1), P=0.01). High GGT serum levels were associated with advanced FIGO stage (P<0.001) and with worse overall survival in univariate (P<0.001) and multivariable analysis (P=0.02, HR 1.2 (1.1-1.5)). We further investigated the association between systemic GGT serum levels and local GGT expression in EOC tumour tissue and observed an association between these two parameters (P=0.03).Conclusion:High pre-therapeutic GGT serum levels are associated with advanced tumour stage and serve as an independent prognostic marker for worse overall survival in patients with EOC. Gamma-glutamyltransferase expression in ovarian cancer tissue is reflected in GGT serum levels.British Journal of Cancer 08/2013; 109(3):610-4. DOI:10.1038/bjc.2013.323 · 4.82 Impact Factor