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), HR
0.71, 95% CI 0.52-0.98; HR
0.65, 0.46-0.92; and HR
1.39, 1.01-1.93). Higher levels of Lp(a) were associated with an increase in prostate cancer risk (Q4 vs. Q1, HR
1.43, 1.02-2.03) and high levels of apo(a) were associated with a decrease in lung cancer risk (Q4 vs. Q1, HR
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, HR
0.71, 0.54-0.94; HR
0.67, 0.50-0.91; HR
0.71, 0.54-0.93; and HR
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.
It has long been proposed that albumin, bilirubin and uric acid may inhibit cancer development due to their anti-oxidative properties. However, there is a lack of population-based studies on blood ...levels of these molecules and cancer risk.
Associations between pre-diagnostic serum albumin, bilirubin and uric acid and the risks of common cancers as well as cancer death in the EPIC-Heidelberg cohort were evaluated by multivariable Cox regression analyses. A case-cohort sample including a random subcohort (n=2739) and all incident cases of breast (n=627), prostate (n=554), colorectal (n=256), and lung cancer (n=195) as well as cancer death (n=761) that occurred between baseline (1994-1998) and 2009 was used.
Albumin levels were inversely associated with breast cancer risk (hazard ratio
(95% CI): 0.71 (0.51, 0.99), P
=0.004) and overall cancer mortality (HR
(95% CI): 0.64 (0.48, 0.86), P
<0.001) after multivariable adjustment. Uric acid levels were also inversely associated with breast cancer risk (HR
(95% CI): 0.72 (0.53, 0.99), P
=0.043) and cancer mortality (HR
(95% CI): 0.75 (0.58, 0.98), P
=0.09). There were no significant associations between albumin or uric acid and prostate, lung and colorectal cancer. Serum bilirubin was not associated with any cancer end point.
The present findings indicate that higher levels of albumin and uric acid are related to lower risks of breast cancer and cancer mortality. Further studies are needed to assess whether the observed associations are causal.
Meat and fish intakes have been associated with various chronic diseases. The use of specific biomarkers may help to assess meat and fish intake and improve subject classification according to the ...amount and type of meat or fish consumed.
A metabolomic approach was applied to search for biomarkers of meat and fish intake in a dietary intervention study and in free-living subjects from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
In the dietary intervention study, 4 groups of 10 subjects consumed increasing quantities of chicken, red meat, processed meat, and fish over 3 successive weeks. Twenty-four-hour urine samples were collected during each period and analyzed by high-resolution liquid chromatography-mass spectrometry. Signals characteristic of meat or fish intake were replicated in 50 EPIC subjects for whom a 24-h urine sample and 24-h dietary recall were available and who were selected for their exclusive intake or no intake of any of the 4 same foods.
A total of 249 mass spectrometric features showed a positive dose-dependent response to meat or fish intake in the intervention study. Eighteen of these features best predicted intake of the 4 food groups in the EPIC urine samples on the basis of partial receiver operator curve analyses with permutation testing (areas under the curve ranging between 0.61 and 1.0). Of these signals, 8 metabolites were identified. Anserine was found to be specific for chicken intake, whereas trimethylamine-
oxide showed good specificity for fish. Carnosine and 3 acylcarnitines (acetylcarnitine, propionylcarnitine, and 2-methylbutyrylcarnitine) appeared to be more generic indicators of meat and meat and fish intake, respectively.
The meat and fish biomarkers identified in this work may be used to study associations between meat and fish intake and disease risk in epidemiologic studies. This trial was registered at clinicaltrials.gov as NCT01684917.
Inclusion of clinical parameters limits the application of most cardiovascular disease (CVD) prediction models to clinical settings. We developed and externally validated a non-clinical CVD risk ...score with a clinical extension and compared the performance to established CVD risk scores. We derived the scores predicting CVD (non-fatal and fatal myocardial infarction and stroke) in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 25,992, cases = 683) using competing risk models and externally validated in EPIC-Heidelberg (n = 23,529, cases = 692). Performance was assessed by C-indices, calibration plots, and expected-to-observed ratios and compared to a non-clinical model, the Pooled Cohort Equation, Framingham CVD Risk Scores (FRS), PROCAM scores, and the Systematic Coronary Risk Evaluation (SCORE). Our non-clinical score included age, gender, waist circumference, smoking, hypertension, type 2 diabetes, CVD family history, and dietary parameters. C-indices consistently indicated good discrimination (EPIC-Potsdam 0.786, EPIC-Heidelberg 0.762) comparable to established clinical scores (thereof highest, FRS: EPIC-Potsdam 0.781, EPIC-Heidelberg 0.764). Additional clinical parameters slightly improved discrimination (EPIC-Potsdam 0.796, EPIC-Heidelberg 0.769). Calibration plots indicated very good calibration with minor overestimation in the highest decile of predicted risk. The developed non-clinical 10-year CVD risk score shows comparable discrimination to established clinical scores, allowing assessment of individual CVD risk in physician-independent settings.
Abstract
Glaucoma is a neurodegenerative disease with a structural change of the optic nerve head, leading to visual field defects and ultimately blindness. It has been proposed that glaucoma is ...associated with increased mortality, but previous studies had methodological limitations (selective study samples, lack of data on potential confounders, self-reported or secondary data on glaucoma diagnoses). We evaluated the association between diagnosed glaucoma and mortality in the population-based National Health and Nutrition Examination Survey (NHANES), a representative health survey in the United States. The survey cycles 2005–2006 and 2007–2008 included an extensive ophthalmic examination with fundus photography, which were used to derive standardized glaucoma diagnoses. Risk of all-cause mortality was assessed with multivariable Cox proportional hazards regression models accounting for the complex survey design of NHANES. Time to death was calculated from the examination date to date of death or December 31, 2015 whichever came first. 5385 participants (52.5% women) were eligible, of which 138 had glaucoma at baseline, and 833 died during follow-up. Participants with glaucoma were more likely to be older than those without glaucoma (mean age 69.9 vs. 56.0 years). Mean follow-up time was 8.4 years for participants with glaucoma, and 8.6 years for participants without glaucoma. Glaucoma was associated with increased mortality in an unadjusted Cox regression model (hazard ratio 2.06, 95% confidence interval 1.16 to 3.66), but the association was no longer statistically significant after adjusting for age and sex (hazard ratio 0.74, 95% confidence interval 0.46 to 1.17). Additional adjustment for a range of potential confounders did not significantly change the results. In this representative population-based study, we found no evidence of increased mortality risk in glaucoma patients.
First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. However, there ...is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk.
Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids, biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal cancer were evaluated by Cox regression analyses using data of a prospective case-cohort study including 835 incident cancer cases.
The median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lysophosphatidylcholines (lysoPCs), and especially lysoPC a C18:0, were consistently related to lower risks of breast, prostate, and colorectal cancer, independent of background factors. In contrast, higher levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity in the observed associations by lag time between blood draw and cancer diagnosis.
Changes in blood lipid composition precede the diagnosis of common malignancies by several years. Considering the consistency of the present results across three cancer types the observed alterations point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis.
Biological age is an important risk factor for chronic diseases. We examined the associations between five markers of unhealthy ageing; Growth Differentiation Factor-15 (GDF-15), N-terminal pro-brain ...natriuretic peptide (NT-proBNP), glycated hemoglobin A1c (HbA1C), C-Reactive Protein (CRP) and cystatin-C; with risks of cancer and cardiovascular disease (CVD). We used a case-cohort design embedded in the EPIC-Heidelberg cohort, including a subcohort of 3792 participants along with 4867 incident cases of cancer and CVD. Hazard ratios (HRs) were computed and the strongest associations were used to build weighted multi-marker combinations, and their associations with cancer and CVD risks were tested. After adjusting for common confounders, we observed direct associations of GDF-15 with lung cancer risk, NT-proBNP with breast, prostate and colorectal cancers, HbA1C with lung, colorectal, and breast cancer risks, and CRP with lung and colorectal cancer risks. An inverse association was observed for GDF-15 and prostate cancer risk. We also found direct associations of all 5 markers with myocardial infarction (MI) risk, and of GDF-15, NT-proBNP, CRP and cystatin-C with stroke risk. A combination of the independently-associated markers showed a moderately strong association with the risks of cancer and CVD (HR
Q4-Q1
ranged from 1.781.36, 2.34 for breast cancer, when combining NT-proBNP and HbA1C, to 2.872.15, 3.83 for MI when combining NT-proBNP, HbA1C, CRP and cystatin-C). This analysis suggests that combinations of biomarkers related to unhealthy ageing show strong associations with cancer risk, and corroborates published evidence on CVD risk. If confirmed in other studies, using these biomarkers could be useful for the identification of individuals at higher risk of age-related diseases.
A balanced diet and sufficient physical activity (PA) are known to have positive health effects. The relationship between a vegan diet and PA levels is understudied. This cross-sectional online ...survey aimed to analyze whether different vegan dietary patterns differ in PA. In total, 516 vegan participants were included (June to August 2022). Different dietary patterns were compiled through principal component analysis, while group differences were calculated using independent tests, or chi-squared tests as well as logistic regression analyses. The population had an average age of 28.0 (SD: 7.7) years and had been living vegan for 2.6 (95% CI: 2.5-3.0) years. Two dietary patterns, the "convenience" and the "health-conscious" group, were identified. People with a convenience dietary pattern had significantly higher odds of sitting more (OR 1.10, 95% CI 1.04-1.18) and not achieving aerobic PA (OR 1.81, 95% CI 1.18-2.79) or strength training recommendations (OR 1.81, 95% CI 1.26-2.61) than people with a health-conscious dietary pattern. This study suggests the heterogeneity of vegan diets and that dietary patterns must be differentiated, as they also differ in the level of PA. Additional studies involving complete dietary assessment with a focus on ultraprocessed foods, blood metabolite analysis, and objective PA assessment are required.
There is preliminary evidence to suggest a positive association between fluoride exposure and higher blood pressure among children, but population-based biomarker studies are lacking. Thus, data from ...the 2013/2014 and 2015/2016 cycles of the US-based National Health and Nutrition Examination Survey (NHANES) were analysed to evaluate the association between plasma fluoride concentrations and blood pressure among children and adolescents aged 8 to 19 years. Secondary analyses were carried out on fluoride status in relation to further markers of cardio-metabolic health, i.e., anthropometric indices, biomarkers of lipid and sugar metabolism, and C-reactive protein levels. There was a positive correlation between water fluoride content and plasma fluoride concentrations (Spearman’s r = 0.41, p < 0.01). However, multivariable linear regression models did not show significant differences in adjusted mean values of systolic and diastolic blood pressure across increasing quartiles of fluoride concentrations. Further markers of cardio-metabolic health were not associated with fluoride status, with the exception of a weak inverse association between plasma fluoride and HbA1c levels. Higher plasma fluoride may not be a risk factor for increased blood pressure or impaired cardio-metabolic health among children in the USA, a non-fluoride endemic country, with wide-spread water fluoridation.
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