Data from Association of γ-Glutamyltransferase and Risk of Cancer Incidence in Men: A Prospective Study (original) (raw)
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Association of -Glutamyltransferase and Risk of Cancer Incidence in Men: A Prospective Study
Cancer Research, 2008
Although several epidemiologic studies have shown that ;-glutamyltransferase (GGT) is independently associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In several experimental models, the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it thus may play a role in tumor progression, as has been repeatedly suggested. We prospectively investigated the association between GGT and risk of overall and site-specific cancer incidence in a large population-based cohort of 79,279 healthy Austrian men with serial GGT measurements. Median follow-up was 12.5 years. Adjusted Cox proportional hazards models were calculated to evaluate GGT as an independent predictor for cancer incidence, and nonparametric regression splines were fitted to flexibly capture the dose-response relationship. Elevated GGT significantly increased overall cancer risk, showing a clear dose-response relationship (P for GGT log-unit increase < 0.0001; P for trend < 0.0001). In comparison with the reference GGT concentration (25 units/L), we found adjusted relative risks (95% confidence intervals) equalling 1.19 (1.15-1.22) for GGT concentrations of 60 units/L, 1.32 (1.28-1.36) for 100 units/L, 1.67 (1.60-1.75) for 200 units/L, and 2.30 (2.14-2.47) for 400 units/L. In cancer site-specific models, GGT was significantly associated with malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, and urinary organs (all P < 0.0001). Age of participants significantly modified the association of GGT and cancer risk (P < 0.001), revealing markedly stronger associations in participants ages V65 years. Our findings, for the first time, show that elevated GGT is significantly associated with increased cancer risk in men.
Association of γ-glutamyltransferase and risk of cancer incidence in men: a prospective study
2008
Although several epidemiologic studies have shown that ;-glutamyltransferase (GGT) is independently associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In several experimental models, the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it thus may play a role in tumor progression, as has been repeatedly suggested. We prospectively investigated the association between GGT and risk of overall and site-specific cancer incidence in a large population-based cohort of 79,279 healthy Austrian men with serial GGT measurements. Median follow-up was 12.5 years. Adjusted Cox proportional hazards models were calculated to evaluate GGT as an independent predictor for cancer incidence, and nonparametric regression splines were fitted to flexibly capture the dose-response relationship. Elevated GGT significantly increased overall cancer risk, showing a clear dose-response relationship (P for GGT log-unit increase < 0.0001; P for trend < 0.0001). In comparison with the reference GGT concentration (25 units/L), we found adjusted relative risks (95% confidence intervals) equalling 1.19 (1.15-1.22) for GGT concentrations of 60 units/L, 1.32 (1.28-1.36) for 100 units/L, 1.67 (1.60-1.75) for 200 units/L, and 2.30 (2.14-2.47) for 400 units/L. In cancer site-specific models, GGT was significantly associated with malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, and urinary organs (all P < 0.0001). Age of participants significantly modified the association of GGT and cancer risk (P < 0.001), revealing markedly stronger associations in participants ages V65 years. Our findings, for the first time, show that elevated GGT is significantly associated with increased cancer risk in men.
Prospective study of the association of gamma‐glutamyltransferase with cancer incidence in women
2008
Although several epidemiologic studies have shown that gammaglutamyltransferase (GGT) is associated with cardiovascular disease and all-cause mortality, its relationship with cancer incidence remains widely unexplored. In experimental models the ability of cellular GGT to modulate crucial redox-sensitive functions has been established, and it may thus play a role in tumor progression. In the present study, we investigated the association of GGT with overall and site-specific cancer incidence in a population-based cohort of 92,843 Austrian women with 349,674 serial GGT measurements, prospectively followed-up for a median of 13.5 years. The relationship between GGT and cancer incidence was analyzed using adjusted Cox regression models with age as underlying time metric with age as underlying time metric including GGT concentrations at baseline and incorporating repeated GGT measurements as a time-dependent variable. During follow-up, 4,884 incidence cancers were observed. Compared to normal low GGT (<17.99 U/L), cancer risk was elevated for all other GGT categories (p for trend < 0.0001), with adjusted hazard ratios (95% confidence intervals) of 1.06 (0.99-1.13) for GGT levels between 18.00 and 35.99 U/L (normal high), 1.12 (1.02-1.22) for GGT levels between 36.00 and 71.99 U/L (elevated) and 1.43 (1.28-1.61) for highly elevated GGT (>72.00 U/L). Very similar results were seen when GGT was analyzed as a time-dependent variable. In cancer-site specific models, elevated GGT statistically significantly increased the risk for malignant neoplasms of digestive organs, the respiratory system/intrathoracic organs, breast and female genital organs and lymphoid and haematopoietic cancers (all, p < 0.006). Our study is the first to demonstrate in a large population-based cohort that high GGT levels significantly increased cancer risk in women.
GSTT1 andGSTM1 gene polymorphisms and gastric cancer in a high-risk italian population
International Journal of Cancer, 2005
Glutathione S-Transferases (GSTs) are a family of phase II enzymes involved in the detoxification of potential carcinogens and provided of a strong antioxidant function by neutralizing electrophiles and free radicals. The GSTM1 and GSTT1 isoenzymes exhibit deletion polymorphisms, resulting in a lack of activity, and the null genotypes have been associated with increased cancer risk at several sites, including the stomach, although with contrasting results. We carried out a case-control study to evaluate whether these polymorphisms modulate the risk of developing gastric cancer (GC). Genotypes for GSTM1 and GSTT1 were obtained from a series of 175 histologically confirmed GC patients and a large series of 546 healthy controls randomly sampled from the general population of Tuscany, an area at high GC risk. No difference in the frequency of GSTM1 null genotype was observed between cases and controls, whereas the GSTT1 null genotype was more frequent among cases (p = 0.04). Multivariate single-gene analyses adjusted for possible confounders showed that the GSTT1 null genotype, but not the GSTM1 null genotype, was associated with an increased GC risk. Combined-genotype analyses showed a significantly increased GC risk only for the double null (GSTM1-GSTT1) genotype (OR = 2.27; 95% CI: 1.14–4.53). A statistically significant positive interaction between the 2 null genotypes was observed (p = 0.02). Our findings suggest that only subjects lacking both GSTM1 and GSTT1 activity are at increased GC risk. This study provides further support to the hypothesis that the risk of developing GC is influenced by inter-individual variation in both carcinogen detoxification and antioxidant capacity. © 2005 Wiley-Liss, Inc.
Circulation, 2005
Background-There is evidence from recent studies that ␥-glutamyltransferase (GGT) is likely to be associated with cardiovascular disease (CVD). However, few studies to date with sufficient sample size and follow-up investigated the association of GGT with CVD mortality. Methods and Results-The relation of GGT to the risk of death from CVD was examined in a cohort of 163 944 Austrian adults that was monitored for up to 17 years. To evaluate GGT as an independent predictor, Cox proportional hazards models were calculated, which adjusted for established risk factors. In both men and women, high GGT was significantly (PϽ0.001) associated with total mortality from CVD, showing a clear dose-response relationship. Adjusted hazard ratios (95% CI) per log GGT increase were 1.66 (1.40 to 1.98) in men and 1.64 (1.36 to 1.97) in women. In men, subgroup analyses showed that high GGT was positively associated with incident fatal events of chronic forms of coronary heart disease (Pϭ0.009), congestive heart failure (PϽ0.001), and hemorrhagic (Pϭ0.01) and ischemic stroke (PϽ0.001). No significant associations were observed for acute myocardial infarction (Pϭ0.16). In women, hazard ratios suggested associations in all subgroups; however, for hemorrhagic and ischemic stroke they were not statistically significant (Pϭ0.09 and Pϭ0.07, respectively). In addition, subgroup analyses stratified by age revealed a stronger relationship of GGT in younger participants. Hazard ratios for total CVD were 2.03 (1.53 to 2.69) in men and 2.60 (1.53 to 4.42) in women younger than 60 years. Conclusions-This study demonstrates in a large, prospectively observed cohort that GGT is independently associated with cardiovascular mortality.
PloS one, 2016
Elevated γ-Glutamyltransferase serum levels are associated with increased risk of overall cancer incidence and several site-specific malignancies. In the present prospective study we report on the associations of serum γ-Glutamyltransferase with the risk of breast cancer in a pooled population-based cohort considering established life style risk factors. Two cohorts were included in the present study, i.e. the Vorarlberg (n = 97,268) and the Malmoe cohort (n = 9,790). Cox proportional hazards regression models were fitted to estimate HRs for risk of breast cancer. In multivariate analysis adjusted for age, body mass index and smoking status, women with γ-Glutamyltransferase levels in the top quartile were at significantly higher risk for breast cancer compared to women in the lowest quartile (HR 1.21, 95% CI 1.09 to 1.35; p = 0.005). In the subgroup analysis of the Malmoe cohort, γ-Glutamyltransferase remained an independent risk factor for breast cancer when additionally considerin...
Gamma Glutamyltransferase and Long-Term Survival: Is It Just the Liver?
Clinical Chemistry, 2007
Background: Increased gamma glutamyltransferase (GGT) is associated with cardiovascular disease. To date, however, few studies with sufficient sample size and follow-up have investigated the association of GGT with all-cause mortality. Methods: The relation of GGT to the risk of death was examined in a cohort of 283 438 first attendants (inpatients or outpatients) of the Vienna General Hospital with request for GGT analysis as part of a routine screening panel and was monitored for up to 13 years. To evaluate GGT as a predictor, Cox proportional hazards models were calculated, which were adjusted for age and sex. Results: In both men and women, GGT above the reference category (GGT ≥9 U/L in women, ≥14 U/L in men) was significantly (P <0.001) associated with all-cause, cancer, hepatobiliary, and vascular mortalities. Hazard ratios (HRs) for men and women were similar in all categories. Among patients who presented with GGT above the reference category, those younger than 30 years...
Cell Biochemistry and Function, 2005
Glutathione S-transferases (GSTs) belong to a superfamily of detoxification enzymes that provide critical defences against a large variety of chemical carcinogens and environmental toxicants. GSTs are present in most epithelial tissues of the human gastrointestinal tract. We investigated associations between genetic variability in specific GST genes (GSTM1, GSTT1 and GSTP1), the interaction with cigarette smoking and susceptibility to gastric cancer. The GSTM1, GSTT1 and GSTP1 polymorphisms were determined using real-time polymerase chain reaction (PCR) and fluorescence resonance energy transfer with Light Cycler Instrument. The study included 70 patients with gastric cancer and 204 controls. Associations between specific genotypes and the development of gastric cancer were examined by use of logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI). The GSTM1 homozygous null genotype was associated with an increased risk of developing gastric cancer (OR ¼ 1.73; 95% CI ¼ 1.10-3.04). GSTT1 homozygous null genotype and GSTP1 genotypes were not associated with the risk of gastric cancer. Also there was no difference between cases and controls in the frequency of val-105 and ile-105 alleles (p ¼ 0.07). After grouping according to smoking status, GSTM1 null genotype was associated with an increased gastric cancer risk for smokers (OR ¼ 2.15; 95% CI, 1.02-4.52). There were no significant differences in the distributions of any of the other GST gene combinations. Our findings suggest that the GSTM1 null genotype may be associated with an increased susceptibility to gastric cancer.
Association between Glutathione-S-Transferase and Gastric Carcinoma: A Case Control Study
Journal of Evolution of Medical and Dental Sciences, 2020
BACKGROUND Gastric carcinoma is the fourth most common cancer type and the second leading cause of cancer deaths worldwide. Every year, around 1 million new cases and 0.7 million deaths are caused due to gastric carcinoma. Gastrointestinal tract is involved in absorption and metabolism of toxic or potentially carcinogenic compounds which may be present in the food we eat. In this context, digestive tract may be considered as a major site of cancer in humans. Glutathione-S-Transferase (GST) is an important metabolizing enzyme, present in the epithelial cells of human GIT. As nearly all reactive, ultimate carcinogenic forms of chemicals are electrophiles, GST is substantially important as a mechanism for carcinogen detoxification. The present study was conducted to evaluate the role of GST in gastric carcinoma and analyse the level of serum GST in patients suffering from gastric carcinoma. METHODS This is a case control study, conducted among 50 cases of gastric carcinoma and 50 age sex matched controls. Patients included in this study were diagnosed with gastric carcinoma, after clinical and histological examination. Circulating levels of GST were assayed in the in the serum of control group and in patients with gastric carcinoma, using standardized method. RESULTS Mean GST activity in serum was significantly higher (p < 0001) in gastric carcinoma patients (8.24 ± 1.94) as compared to control (5.47 ± 0.52). After chemotherapy (12.34 ± 1.05) the activity of GST was significantly higher (p < 0001) than before chemotherapy (10.23 ± 2.12). The generation of free radicals is as reflected by increased GST and GST-π activity in carcinoma cases. CONCLUSIONS Serum GSTs measurement in plasma may be a useful tumour marker in stomach cancer and serum GSTs activity might be helpful in predicting the response of chemotherapy in advanced stages of cancer. GST values are helpful in predicting the radiation response. Overexpression of GST in neoplasia may be causal, allowing replicative advantage, or casual, accompanying clonal expansion. The major limitation to its widespread use is the time needed for doing the assay and until this is overcome it will remain primarily a research tool.