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

King's College London, School of Medicine, Division of Cancer Studies, Cancer Epidemiology Unit, London, UK.
European journal of cancer (Oxford, England: 1990) (Impact Factor: 5.42). 04/2011; 47(13):2033-41. DOI: 10.1016/j.ejca.2011.03.010
Source: PubMed


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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    • "were more likely to be resistant to platinum-containing chemotherapy subsequently leading to a worse prognosis (Hanigan et al, 1999). Recently, large epidemiologic studies revealed that plasma GGT was associated with an increased risk of developing cancer (Strasak et al, 2008a,b; Fentiman and Allen, 2010; Van Hemelrijck et al, 2011). With respect to gynaecologic malignancies, increased GGT serum levels were associated with an increased risk for cervical cancer in a prospective epidemiological cohort study comprising 79 279 women (Strasak et al, 2008a). "
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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.
    Full-text · Article · Aug 2013 · British Journal of Cancer
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    • "The AMORIS cohort contains mainly individuals from the greater Stockholm area, most of whom are aged between 20 and 80 years. The study has been described in detail elsewhere [10] [11] [12]. "
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    ABSTRACT: Objective: The aim was to investigate country or region of birth-specific prevalence and gender differences of diabetes in residents in Sweden, using Swedish-born men and women as referent. Methods: The Apolipoprotein MOrtality RISk (AMORIS) cohort was used (184,000 men and 151,453 women) aged between 20 and 80 years, with data from the CALAB laboratory, Stockholm, 1985-1996. Diabetes was defined as fasting glucose ≥ 7.0 mmol/L or a hospital diagnosis of diabetes. Country of birth was obtained by linkage to Swedish Censuses 1970-1990. Standardized prevalence rate ratios (SPRR) with 95% confidence intervals (95% CI) were estimated. Results: Five groups of women and one group of men had a significantly higher prevalence than Swedish-born (based on SPRR): women born in Iraq (6.0 (95% CI 1.3-28.9)), North Africa (6.9 (95% CI 3.1-15.3)), South Asia (3.1 (95% CI 1.0-10.0)), Syria (5.3 (95% CI 1.8-16.0)), Turkey (3.7 (95% CI 1.2-10.9)) and men born in other Middle Eastern countries (2.3 (95% CI 1.0-5.5)). Swedish-born men had a higher age-standardized prevalence of diabetes (3.9%) than Swedish born women (2.5%). A higher prevalence among men was also seen in other Western countries. In contrast, a higher age-standardized prevalence among women was observed in immigrants from Turkey (8.9% vs. 3.1%, p<0.001), Syria (13.1% vs. 4.0%, p=0.002), and North Africa (16.8% vs. 6.6%, p<0.001). Conclusion: Female immigrants to Sweden from Iraq, North Africa, South Asia, Syria, and Turkey have an increased prevalence of diabetes of substantial public health concern.
    Full-text · Article · Apr 2013 · Diabetes research and clinical practice
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    • "While these previous studies do present interesting data, due to missing data on hypertension and BMI we will focus on dyslipidemia and hyperglycaemia. We assessed whether the direct associations between elevated levels of these biomarkers and dyslipidemia and hypertriglyceridemia were observed in a Swedish population with the use of a large, well-defined database [15] [16] [17] [18]. "
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    ABSTRACT: Recent studies suggested that gamma-glutamyl transferase (GGT) and C-reactive protein (CRP) are good markers of metabolic abnormalities. We assessed the link between GGT, CRP and common metabolic abnormalities, as well their link to related diseases, such as cancer and cardiovascular disease (CVD). We selected 333,313 subjects with baseline measurements of triglycerides (TG), total cholesterol (TC), glucose, GGT and CRP in the Swedish AMORIS study. Baseline measurement of BMI was available for 63,900 persons and 77,944 had baseline measurements of HDL. Pearson correlation coefficients between CRP, GGT, and metabolic components (TG, HDL, BMI and TC) were calculated. To investigate the combined effect of GGT and CRP we created a score ranging from 0 to 6 and used Cox proportional hazard models to evaluate its association with CVD and cancer. 21,216 individuals developed cancer and 47,939 CVD. GGT and TG had the strongest correlation (r=0.22). An increased risk of cancer was identified with elevated levels of GGT or CRP or both markers (GGT-CRP score ≥3); the greatest risk of cancer was found when GGT-CRP score = 6 (HR: 1.40 (95%CI: 1.31-1.48) and 1.60 (1.47-1.76) compared to GGT-CRP score = 0, respectively). While GGT and CRP have been shown to be associated with metabolic abnormalities previously, their association to the components investigated in this study was limited. Results did demonstrate that these markers were predictive of associated diseases, such as cancer.
    Full-text · Article · Dec 2012 · International Journal of Molecular Epidemiology and Genetics
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