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Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-Heidelberg case-cohort study.

ABSTRACT: OBJECTIVES:Elevated liver enzyme concentrations in blood are indicative of liver diseases and may provide an early signal for being at risk for other chronic diseases. Our study aimed to assess the relationships of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate transaminase (AST) and the De Ritis ratio (AST/ALT) with incidence and mortality of cardiovascular diseases (CVD) and the four most common cancers, that is, breast, prostate, colorectal and lung. SETTING, PARTICIPANTS AND OUTCOME MEASURES:We analysed a case-cohort sample of the prospective European Prospective Investigation into Cancer and Nutrition-Heidelberg cohort, including cancer (n=1632), cancer mortality (n=761), CVD (n=1070), CVD mortality (n=381) and a random subcohort (n=2739) with an average follow-up duration of 15.6 years. Concentrations of liver enzymes were measured in prediagnostic blood samples and Prentice-weighted Cox regression models were used to estimate HRs with 95% CIs. RESULTS:High ALP levels were associated with increased risk for lung cancer and all-cause mortality (highest vs lowest quartile, multivariable adjusted HR=2.39 (95% CI 1.30 to 4.39), HR=1.31 (95% CI 1.02 to 1.67)), high AST levels with all-cause mortality (HR=1.45 (95% CI 1.15 to 1.82)), and a high De Ritis ratio with prostate cancer risk, all-cause and cancer mortality (HR=1.61 (95% CI 1.10 to 2.36), HR=1.60 (95% CI 1.25 to 2.04), HR=1.67 (95% CI 1.26 to 2.23)). Using cut-points for liver enzyme levels above normal, we observed positive associations for all-cause mortality with ALP, GGT and AST, and assigning a combined risk score resulted in positive associations with all-cause and cause-specific mortality. CONCLUSIONS:Measurements of serum liver enzymes, as routinely performed in health check-ups, may support the identification of individuals at increased risk for all-cause mortality. Further prospective studies are needed to verify our first results on individual cancers and on a combined risk score.

SUBMITTER: Katzke V

PROVIDER: S-EPMC7064128 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-Heidelberg case-cohort study.

Katzke Verena V Johnson Theron T Sookthai Disorn D Hüsing Anika A Kühn Tilman T Kaaks Rudolf R

BMJ open 20200308 3

<h4>Objectives</h4>Elevated liver enzyme concentrations in blood are indicative of liver diseases and may provide an early signal for being at risk for other chronic diseases. Our study aimed to assess the relationships of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), alanine aminotransferase (ALT), aspartate transaminase (AST) and the De Ritis ratio (AST/ALT) with incidence and mortality of cardiovascular diseases (CVD) and the four most common cancers, that is, breast, prostate, ...[more]

PMID: 32152162

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Project description:Circulating concentrations of lipid biomarkers are associated with risk of cardiovascular diseases (CVD). The evidence for a relationship with cancer risk, however, is not entirely consistent. This study aims to assess the relationships of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), apolipoprotein (a) (apo(a)), apoB-100, and lipoprotein(a) (Lp(a)) with risk of common cancer forms and total cancer mortality in comparison to incidence and mortality of CVD.We selected a case-cohort sample out of the prospective EPIC-Heidelberg study, including a random subcohort (n?=?2739), and cases of cancer (n?=?1632), cancer mortality (n?=?761), CVD (n?=?1070), and CVD mortality (n?=?381). Concentrations of lipid biomarkers were measured in pre-diagnostic blood samples. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Prentice-weighted Cox regression models.High levels of circulating apoB-100 and TG were inversely associated and high HDL-C levels were positively associated with breast cancer risk (highest vs. lowest quartile (Q4 vs. Q1), HRapoB 0.71, 95% CI 0.52-0.98; HRTG 0.65, 0.46-0.92; and HRHDL 1.39, 1.01-1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HRLp(a) 1.43, 1.02-2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HRapo(a) 0.52, 0.30-0.91). High TC, HDL-C, apo(a), and Lp(a) levels were associated with a reduction in total cancer mortality (Q4 vs. Q1, HRTC 0.71, 0.54-0.94; HRHDL 0.67, 0.50-0.91; HRapo(a) 0.71, 0.54-0.93; and HRLp(a) 0.74, 0.57-0.98). All lipid biomarkers were associated with risk of myocardial infarction, whereby TC, apoB-100, TG, and Lp(a) were positively and HLD-C and apo(a) inversely associated with risk. Only high levels of TG were associated with an increased risk of stroke. None of the lipids were associated with risk of colorectal cancer and with risk of CVD mortality after multivariable adjustments.This prospective study demonstrates inverse associations of lipid biomarkers with cancer incidence and mortality, with the exception of positive associations of HDL-C and Lp(a) with breast and prostate cancer risk, respectively. Thus, the observed cancer risk pattern clearly differs from the CVD risk pattern.

Project description:BackgroundAlcohol consumption is an important risk factor for hepatic neoplastic and non-neoplastic diseases. Questions remain, however, about the relevance to disease risk of drinking patterns and alcohol tolerability, which differ appreciably between Chinese and Western populations.MethodsThe prospective China Kadoorie Biobank included 512,715 adults (41% men) aged 30-79 years recruited from ten areas during 2004-2008, recording alcohol intake, drinking patterns, and other characteristics. After median 10 years' follow-up, 2531 incident liver cancer, 2040 liver cirrhosis, 260 alcoholic liver disease (ALD), and 1262 non-alcoholic fatty liver disease (NAFLD) cases were recorded among 492,643 participants without prior cancer or chronic liver disease at baseline. Cox regression was used to estimate adjusted hazard ratios (HR) relating alcohol intake and drinking patterns to each disease.ResultsOverall, 33% of men and 2% of women drank alcohol regularly (i.e. at least weekly) at baseline. Among male current regular drinkers, alcohol consumption showed positive dose-response associations with risks of several major chronic liver diseases, with HRs per 280 g/week (i.e. around four drinks/day) higher usual alcohol intake of 1.44 (95% CI 1.23-1.69) for liver cancer (n = 547), 1.83 (1.60-2.09) for liver cirrhosis (n = 388), 2.01 (1.77-2.28) for ALD (n = 200), 1.71 (1.35-2.16) for NAFLD (n = 198), and 1.52 (1.40-1.64) for total liver disease (n = 1775). The association with ALD appeared stronger among men reporting flushing (i.e., with low alcohol tolerance). After adjustment for the total amount of weekly alcohol consumption, daily drinkers had significantly increased risk of ALD (2.15, 1.40-3.31) compared with non-daily drinkers, and drinking without meals was associated with significantly greater risks of liver cancer (1.32, 1.01-1.72), liver cirrhosis (1.37, 1.02-1.85), and ALD (1.60, 1.09-2.33) compared with drinking with meals. Female current regular drinkers had significantly higher risk of ALD, but not other liver diseases, than female abstainers.ConclusionsIn Chinese men, alcohol intake was associated with significantly increased risks of several major chronic liver diseases, and certain drinking patterns (e.g. drinking daily, drinking without meals) may further exacerbate the disease risks.

Project description:BACKGROUND:Experimental and epidemiological studies demonstrate a role for 27-hydroxycholesterol (27HC) in breast cancer development, though results are conflicting. Cholesterol 27-hydroxylase (CYP27A1) and oxysterol 7-alpha-hydroxylase (CYP7B1) regulate 27HC concentrations, while differential expression of the liver X receptor (LXR) and estrogen receptor beta (ER?) may impact the association between 27HC and breast cancer risk. METHODS:We evaluated correlates of tumor tissue expression of CYP27A1, CYP7B1, LXR-?, and ER? and the association between circulating prediagnostic 27HC concentrations and breast cancer risk by marker expression in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Heidelberg cohort including 287 breast cancer cases with tumor tissue available. Tumor protein expression was evaluated using immunohistochemistry, and serum 27HC concentrations quantified using liquid chromatography-mass spectrometry. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:A higher proportion of CYP7B1-positive cases were progesterone receptor (PR)-positive, relative to CYP7B1-negative cases, whereas a higher proportion of ER?-positive cases were Bcl-2 low, relative to ER?-negative cases. No differences in tumor tissue marker positivity were observed by reproductive and lifestyle factors. We observed limited evidence of heterogeneity in associations between circulating 27HC and breast cancer risk by tumor tissue expression of CYP27A1, CYP7B1, LXR-?, and ER?, with the exception of statistically significant heterogeneity by LXR-? status in the subgroup of women perimenopausal at blood collection (p?=?0.02). CONCLUSION:This exploratory study suggests limited associations between tumor marker status and epidemiologic or breast cancer characteristics. Furthermore, the association between circulating 27HC and breast cancer risk may not vary by tumor expression of CYP27A1, CYP7B1, LXR-?, or ER?.

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Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-Heidelberg case-cohort study.

Publications

Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-Heidelberg case-cohort study.

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