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γ-Glutamyltransferase and Breast Cancer Risk Beyond Alcohol Consumption and Other Life Style Factors - A Pooled Cohort Analysis.

ABSTRACT: 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 considering alcohol intake. A statistically significant increase in risk was seen in women with γ-Glutamyltransferase-levels in the top versus lowest quartile in a multivariate model adjusted for age, body mass index, smoking status, physical activity, parity, oral contraceptive-use and alcohol consumption (HR 1.37, 95% CI 1.11-1.69, p = 0.006).Our findings identified γ-Glutamyltransferase as an independent risk factor for breast cancer beyond the consumption of alcohol and other life style risk factors.

SUBMITTER: Preyer O

PROVIDER: S-EPMC4749274 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Serum Gamma-Glutamyltransferase, Daily Alcohol Consumption, and the Risk of Chronic Kidney Disease: The Kansai Healthcare Study.

Project description:BackgroundSerum gamma-glutamyltransferase has been recognized as the risk factor of cardiovascular and metabolic diseases. However, the association between serum gamma-glutamyltransferase and the risk of chronic kidney disease is not well known, and no prospective studies have examined separately the relationship of serum gamma-glutamyltransferase with the risk of proteinuria versus that of low estimated glomerular filtration rate (eGFR).MethodsWe prospectively followed 9,341 Japanese men who did not have low eGFR, proteinuria, or diabetes, and did not take antihypertensive medications at entry for the analysis of proteinuria, and we followed 9,299 men for the analysis of low eGFR. We defined "persistent proteinuria" as proteinuria detected two or more times consecutively and persistently as ≥1+ on urine dipstick at the annual check-up until the end of follow-up. Low eGFR was defined as eGFR <60 mL/min/1.73 m2.ResultsDuring the 11-year observation period, 151 men developed persistent proteinuria and 1,276 men developed low eGFR. In multivariate models, the highest quartile (≥71 IU/L) of serum gamma-glutamyltransferase was independently related to the development of persistent proteinuria (hazard ratio 3.39; 95% confidence interval, 1.92-5.97) compared with the lowest quartile (≤25 IU/L). In joint analysis of alcohol consumption and serum gamma-glutamyltransferase, non-drinkers in the highest tertile (≥58 IU/L) of serum gamma-glutamyltransferase had the highest risk of persistent proteinuria. However, there was no association between serum gamma-glutamyltransferase and low eGFR.ConclusionIn middle-aged Japanese men, elevated serum gamma-glutamyltransferase was independently associated with future persistent proteinuria, but not with low eGFR.

| S-EPMC7064553 | biostudies-literature

Alcohol Use and Gamma-Glutamyltransferase Using a Mendelian Randomization Design in the Guangzhou Biobank Cohort Study.

Project description:BackgroundObservational studies and small intervention studies suggest alcohol raises gamma-glutamyltransferase (GGT). We used Mendelian randomization to assess the causal effect of alcohol use on GGT in older Chinese people.MethodsAn instrumental variable (IV) analysis in 2,321 men and 2,757 women aged 50+ years from phase 3 of the Guangzhou Biobank Cohort Study with ALDH2 (rs671) genotyped, alcohol use and GGT available was used to assess the causal effect of alcohol use on GGT. Rs671 was used as an IV and F-statistics was used to test for weak instrument hypothesis. An F-statistic of ≥10 indicates the IV is not weak.ResultsIn men, the F-statistic for rs671 on alcohol use was 70. Using IV analysis alcohol use increased GGT by 10.60 U/L per alcohol unit (10 gram ethanol) per day (95% confidence interval (CI) 6.58 to 14.62). The estimate was lower in observational multivariate regression: 3.48 U/L GGT per alcohol unit per day (95% CI 2.84 to 4.11) adjusted for age, education, physical activity and smoking. In women, rs671 was not associated with alcohol or GGT and the F-statistic was 7 precluding IV analysis.ConclusionIn Mendelian randomization, we found confirmative evidence that alcohol use increases GGT among Southern Chinese men. Moreover, we found that the ALDH2 variant rs671 was not associated with GGT among Southern Chinese women who generally consume very low levels of alcohol. Taken together our findings strongly suggest that alcohol increases GGT, although we cannot rule out the possibility that other unknown factors may cause a different relation between alcohol and GGT in other populations.

| S-EPMC4565586 | biostudies-literature

Smoking and ?-glutamyltransferase: opposite interactions with alcohol consumption and body mass index.

Project description:BACKGROUND: Smoking has recently been suggested to synergistically interact with alcohol intake as a determinant of serum gamma-glutamyltransferase (?-GT), an emergent powerful predictor of disease and mortality. This study investigated whether this also applies to higher smoking and alcohol exposure ranges and to body mass index (BMI), which likewise is strongly associated with ?-GT. METHODOLOGY/PRINCIPAL FINDINGS: Analyses were based on occupational health examinations of more than 15,000 German male workers aged 16-64 years, predominantly from the construction industry. Sociodemographics and other health-related information were collected during the exam. Joint associations of smoking and alcohol consumption or BMI with elevated or log-transformed ?-GT were examined by tabulation and multiple adjusted regression models. Cigarette smoking exerted no effect on ?-GT in teetotalers, but there was a statistically significant effect of smoking among participants with higher alcohol consumption intensity, odds of elevated ?-GT being increased by 24% and 27% per additional 10 cigarettes smoked per day in subjects drinking 61-90 and >90 gram alcohol per day, respectively (P for interaction = 0.039). The interaction was opposite for BMI, where no association was seen in obese subjects, whereas odds of elevated ?-GT were increased by 24% per 10 cigarettes below 25 kg/m(2) (P for interaction = 0.040). This novel interaction was replicable in an independent cohort. CONCLUSION: The evidence for opposite interactions of smoking with alcohol and BMI as determinants of serum ?-GT suggests that different physiological pathways are responsible for the associations between these factors.

| S-EPMC2948041 | biostudies-literature

Personality and alcohol consumption: Pooled analysis of 72,949 adults from eight cohort studies.

Project description:BackgroundThe role of personality as a determinant of alcohol consumption has long been debated, but prospective evidence is scarce.MethodsWe performed individual participant meta-analysis to examine the association between the Five-Factor Model personality traits (extraversion, neuroticism, agreeableness, conscientiousness, and openness to experience) and alcohol consumption using data from eight cohort studies sampled from the USA, UK, Germany, and Australia (total n=72,949; mean age=50 years, 54% female). Alcohol consumption was categorized into abstinence, moderate consumption, and heavy consumption.ResultsAfter adjustment for age, sex, and race, higher extraversion (odds ratio for 1 standard deviation's increase in the score; 95% confidence interval: 1.14; 1.01-1.29) and lower conscientiousness (0.89; 0.79-1.00) were associated with increased risk of transitioning from moderate to heavy alcohol consumption over time, and also with heavy alcohol consumption. Lower extraversion (0.91; 0.85-0.98), higher agreeableness (1.09; 1.02-1.15), and lower openness (0.90; 0.86-0.95) were associated with increased odds of transitioning from moderate consumption to abstinence as well as with alcohol abstinence.ConclusionFindings from this individual-participant meta-analysis suggest that high and increasing alcohol consumption is more common among extraverts and those low on conscientiousness whereas high agreeableness and low openness to experience may increase odds of reducing alcohol consumption and preferring abstinence.

| S-EPMC4447572 | biostudies-literature

Highly Elevated Plasma γ-Glutamyltransferase Elevations: A Trait Caused by γ-Glutamyltransferase 1 Transmembrane Mutations.

Project description: Not available

| S-EPMC7155009 | biostudies-literature

Alcohol consumption in later life and reaching longevity: the Netherlands Cohort Study.

Project description:Backgroundwhether light-to-moderate alcohol intake is related to reduced mortality remains a subject of intense research and controversy. There are very few studies available on alcohol and reaching longevity.Methodswe investigated the relationship of alcohol drinking characteristics with the probability to reach 90 years of age. Analyses were conducted using data from the Netherlands Cohort Study. Participants born in 1916-1917 (n = 7,807) completed a questionnaire in 1986 (age 68-70 years) and were followed up for vital status until the age of 90 years (2006-07). Multivariable Cox regression analyses with fixed follow-up time were based on 5,479 participants with complete data to calculate risk ratios (RRs) of reaching longevity (age 90 years).Resultswe found statistically significant positive associations between baseline alcohol intake and the probability of reaching 90 years in both men and women. Overall, the highest probability of reaching 90 was found in those consuming 5- < 15 g/d alcohol, with RR = 1.36 (95% CI, 1.20-1.55) when compared with abstainers. The exposure-response relationship was significantly non-linear in women, but not in men. Wine intake was positively associated with longevity (notably in women), whereas liquor was positively associated with longevity in men and inversely in women. Binge drinking pointed towards an inverse relationship with longevity. Alcohol intake was associated with longevity in those without and with a history of selected diseases.Conclusionsthe highest probability of reaching 90 years was found for those drinking 5- < 15 g alcohol/day. Although not significant, the risk estimates also indicate to avoid binge drinking.

| S-EPMC7187870 | biostudies-literature

Genetically elevated gamma-glutamyltransferase and Alzheimer's disease.

Project description:Observational epidemiological evidence supports a linear and independent association between serum gamma-glutamyltransferase (GGT) concentrations and the risk of Alzheimer's disease (AD). However, the causality of this association has not been previously investigated. We sought to assess the causal nature of this association using a Mendelian randomization (MR) approach. Using inverse-variance weighted MR analysis, we assessed the association between GGT and AD using summary statistics for single nucleotide polymorphism (SNP)-AD associations obtained from the International Genomics of Alzheimer's Project of 17,008 individuals with AD and 37,154 controls. We used 26 SNPs significantly associated with GGT in a previous genome-wide association study on liver enzymes as instruments. Sensitivity analyses to account for potential genetic pleiotropy included MR-Egger and weighted median MR. The odds ratio of AD was 1.09 (95% confidence interval, 0.98 to 1.22; p = 0.10) per one standard deviation genetically elevated GGT based on all 26 SNPs. The results were similar in both MR-Egger and weighted median MR methods. Overall, our findings cannot confirm a strong causal effect of GGT on AD risk. Further MR investigations using individual-level data are warranted to confirm or rule out causality.

| S-EPMC5915296 | biostudies-literature

Reasons why people change their alcohol consumption in later life: findings from the Whitehall II Cohort Study.

Project description:Harmful alcohol consumption among the ageing population is an important public health issue. Very few studies ask drinkers why they change their consumption in later life. The aim of this paper was to determine whether a group of people aged over 60 years increased or decreased their alcohol consumption over the past decade and to determine the reasons for their change. We also examined whether the responses varied by age, sex and socio-economic position (SEP).Data were taken from 6,011 participants (4,310 men, 1,701 women, age range 61 to 85 years) who completed questionnaires at phase 11 (2012-2013) of the Whitehall II Cohort Study.Over half the study members reported a change in alcohol consumption over the past decade (40% decreased, 11% increased). The most common reasons given for decreases were as a health precaution and fewer social occasions. Common reasons for increases were more social occasions and fewer responsibilities. The lowest SEP group was less likely to increase consumption compared to high SEP (RR 0.57, 95% CI 0.40 to 0.81). Women were more likely to increase consumption in response to stress/depression than men (RR1.53, 95% CI 1.04 to 2.25). Compared to high SEP, the lowest SEP group was less likely to reduce as a health precaution (RR 0.61, 95% CI 0.38 to 0.76).Alcohol consumption in late life is not fixed. Reasons for change vary by age, sex and SEP. Such information could be used to tailor intervention strategies to reduce harmful consumption.

| S-EPMC4355077 | biostudies-other

Modifiable life style factors and risk for incident endometriosis.

Project description:BackgroundCaffeine, alcohol, smoking and physical activity are known to alter sex steroid synthesis, which may affect hormone-dependent gynaecologic disease risk, such as endometriosis; however, few studies have assessed life style factors prior to endometriosis diagnosis.MethodsFour hundred and seventy three women, ages 18-44 years, underwent laparoscopy or laparotomy, regardless of clinical indication, at 14 clinic sites, 2007-2009. Women with prior surgically confirmed endometriosis were excluded. Life style factors were assessed prior to surgery. Adjusted risk ratios (RR) of endometriosis by caffeine, alcohol, smoking (serum cotinine), and physical activity were estimated, adjusting for age, marital status, education, race/ethnicity, age at menarche, gravidity, BMI, study site, and other life style factors.ResultsThere were no associations between women with endometriosis and alcohol consumption (RR 0.9, 95% CI 0.7, 1.3), caffeine consumption (RR 1.1, 95% CI 0.8, 1.5), or smoking (serum cotinine <10 vs ≥10 ng/mL; RR 1.0, 95% CI 0.7, 1.6). Similar null findings were found between endometriosis and weekly occurrences of physical activity and total walking, moderate, and vigorous activity; a modest trend was found between total daily sitting time and increased endometriosis risk.ConclusionsThis study, which is unique in its capture of life style exposures prior to incident endometriosis diagnosis, largely found no association between alcohol, caffeine, smoking, and physical activity and risk of endometriosis.

| S-EPMC6353682 | biostudies-literature

Gamma-glutamyltransferase and risk of cardiovascular mortality: A dose-response meta-analysis of prospective cohort studies.

Project description:BackgroundSerum gamma-glutamyltransferase (GGT) elevation likely contributes to cardiovascular (CV) mortality, however it has remained unknown whether a dose-response relationship exists between serum GGT and CV mortality.MethodsWe searched the PubMed, EMBASE, and Cochrane library databases for prospective cohort studies published up to October 2, 2016. Summary hazard ratios (HRs) with their corresponding 95% confidence intervals (CIs) were calculated using a fixed effects model.FindingsNine prospective studies, including 527,589 participants and more than 7,011 cases, were included in this meta-analysis. For the moderate, high, and highest levels of GGT, the pooled HRs of CV mortality were 1.11 (95% CI = 1.04-1.19), 1.29 (95% CI = 1.21-1.38) and 1.59 (95% CI = 1.47-1.72), respectively (all p < 0.05 as compared to the lowest levels of GGT). Additionally, the HR per incremental increase of GGT by 10 U/L was 1.10 (95% CI = 1.08-1.11). Evidence of a positive relationship with nonlinear trend for GGT elevation with CV mortality in females was found (P = 0.04 for nonlinearity). However, a linear model was better fit to illustrate the GGT-CV mortality among males (P = 0.304 for nonlinearity).ConclusionsThese findings indicate that serum GGT activity within the reference interval is positively associated with increased risk of CV mortality in a dose-response manner.

| S-EPMC5322906 | biostudies-literature

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