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Nick Wareham

Publications and source records attributed to Nick Wareham.

10 recordsLinked to original sources
PubMed2026

Immune Markers and Risk of Pancreatic Cancer in the European EPIC Cohort.

The immune system is a major driver in pancreatic cancer development. Several prospective cohort studies have found associations for single immune system-derived proteins such as IL6 or CRP, but results are inconclusive, and Omics-based research is scarce. Hence, we aimed to investigate associations of a comprehensive protein panel with the risk of pancreatic cancer. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, 92 immune proteins were measured in baseline blood samples of 406 incident pancreatic cancer cases and 406 sex- and age-matched controls, using the Olink Immuno-Oncology panel. Multivariable adjusted conditional logistic regression was used to estimate odds ratios (OR, 95% CI) for protein levels in association with pancreatic cancer risk. Eight biomarkers were associated with pancreatic cancer risk (MMP12, LAMP3, CD28, IL-6, IL-12, FASLG, PD-L2, and PDCD1) but only MMP12 was significantly associated after multivariable adjustments for confounders and the seven proteins, with OR = 1.56 (95% CI: 1.20-2.03) for a doubling in protein concentration. After correction for multiple testing, none of the proteins were associated with risk. Restricting analyses to cases diagnosed within the first 4 years and 4-8 years after recruitment resulted in OR of 1.89 (95% CI: 1.28-2.80) and 1.37 (95% CI: 1.01-1.86) for MMP12, respectively. Higher levels of MMP12 were associated with pancreatic cancer risk specifically in those diagnosed shortly after recruitment, while other immune-related factors were not associated with risk. Further cohort studies are needed to confirm our initial findings.

Humans↗
PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention. FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University M&#xfc;nster.

Journal Article↗
PubMed2025

Redefining ALS: Large-scale proteomic profiling reveals a prolonged pre-diagnostic phase with immune, muscular, metabolic, and brain involvement.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder with a largely unknown duration and pathophysiology of the pre-diagnostic phase, especially for the common non-monogenic form. METHODS: We leveraged the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort with up to 30 years of follow-up to identify incident ALS cases across five European countries. Pre-diagnostic plasma samples from initially healthy participants underwent high-throughput proteomic profiling (7,285 protein markers, SomaScan). Cox proportional hazards models based on 4,567 participants (including 172 incident ALS cases) were used to identify protein biomarkers associated with future ALS diagnosis. Top results were indirectly validated in two independent case-control studies of prevalent ALS (n=417 ALS, 852 controls). Functional annotation included cross-disease comparisons, gene set and tissue enrichment testing, organ-specific proteomic clocks, and the application of large-language models (LLM). FINDINGS: Five proteins (SECTM1, CA3, THAP4, KLHL41, SLC26A7) were identified as significant pre-diagnostic ALS biomarkers (FDR=0.05), detectable approximately two decades before diagnosis. Of these, all except SECTM1 were indirectly validated in independent cohorts of prevalent ALS cases, supporting their clinical significance. Additionally, 22 nominally significant (p<0.05) pre-diagnostic biomarkers were FDR-significant in prevalent ALS with consistent effect directions. Cross-disease comparisons with pre-diagnostic Parkinson's and Alzheimer's disease suggested a largely specific pre-diagnostic ALS biomarker signature. Gene ontology and tissue enrichment highlighted early involvement of immune, muscle, metabolic, and digestive processes. Furthermore, analyses of proteomic clocks revealed accelerated aging in brain-cognition, immune, and muscle tissues before clinical diagnosis. Druggability and LLM analyses revealed possible therapeutic targets and novel strategies, emphasizing translational relevance. INTERPRETATION: Our study provides first evidence of ultra-early molecular changes in common ALS up to two decades prior to clinical onset, mainly affecting immune, muscle, metabolic, digestive, and cognitive systems. Our study nominates several compelling candidates for risk stratification studies and novel therapeutic targets for early intervention. FUNDING: Clinical Research in ALS and Related Disorders for Therapeutic Development (CreATe) Consortium, Cure Alzheimer's Fund, Michael J Fox Foundation, Interdisciplinary Centre for Clinical Research, University M&#xfc;nster.

Journal Article↗
PubMed2006

Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 Western prospective studies.

BACKGROUND: Many epidemiological studies have reported on associations between serum triglyceride concentrations and the risk of coronary heart disease, but this association has not been reliably quantified. In the present study, we report 2 separate nested case-control comparisons in 2 different prospective, population-based cohorts, plus an updated meta-analysis of 27 additional prospective studies in general Western populations. METHODS AND RESULTS: Measurements were made in a total of 3582 incident cases of fatal and nonfatal coronary heart disease and 6175 controls selected from among the 44,237 men and women screened in the Reykjavik and the European Prospective Investigation of Cancer (EPIC)-Norfolk studies. Repeat measurements were obtained an average of 4 years apart in 1933 participants in the EPIC-Norfolk Study and an average of 12 years apart in 379 participants in the Reykjavik study. The long-term stability of log-triglyceride values (within-person correlation coefficients of 0.64 [95% CI, 0.60 to 0.68] over 4 years and 0.63 [95% CI, 0.57 to 0.70] over 12 years) was similar to those of blood pressure and total serum cholesterol. After adjustment for baseline values of several established risk factors, the strength of the association was substantially attenuated, and the adjusted odds ratio for coronary heart disease was 1.76 (95% CI, 1.39 to 2.21) in the Reykjavik study and 1.57 (95% CI, 1.10 to 2.24) in the EPIC-Norfolk study in a comparison of individuals in the top third with those in the bottom third of usual log-triglyceride values. Similar overall findings (adjusted odds ratio, 1.72; 95% CI, 1.56 to 1.90) were observed in an updated meta-analysis involving a total of 10,158 incident coronary heart disease cases from 262,525 participants in 29 studies. CONCLUSIONS: Available prospective studies in Western populations consistently indicate moderate and highly significant associations between triglyceride values and coronary heart disease risk. Because these associations depend considerably on levels of established risk factors, however, further studies are needed to help assess the nature of any independent associations.

Case-Control Studies↗
PubMed2006

A road map for efficient and reliable human genome epidemiology.

Networks of investigators have begun sharing best practices, tools and methods for analysis of associations between genetic variation and common diseases. A Network of Investigator Networks has been set up to drive the process, sponsored by the Human Genome Epidemiology Network. A workshop is planned to develop consensus guidelines for reporting results of genetic association studies. Published literature databases will be integrated, and unpublished data, including 'negative' studies, will be captured by online journals and through investigator networks. Systematic reviews will be expanded to include more meta-analyses of individual-level data and prospective meta-analyses. Field synopses will offer regularly updated overviews.

Databases, Factual↗
PubMed2005

Long-term cryoconservation and stability of vitamin C in serum samples of the European prospective investigation into cancer and nutrition.

Plasma vitamin C level may be associated with risk of some chronic diseases. The rapid degradability of vitamin C in biological samples necessitates its stabilization with metaphosphoric acid or similar agents. However, in most cohort studies, prospectively collected biological samples are not treated with stabilizing agents before long-term frozen storage and it is not known whether vitamin C can be properly measured in such samples. The objective of this study was to determine the degree of vitamin C degradation in plasma samples stored without stabilization for 7 to 11 years at -196 degrees C. Spearman's correlation coefficients indicate a moderate correlation between baseline and final plasma vitamin C levels in both men (r = 0.57, P < 0.0001) and women (r = 0.52, P < 0.0001). Samples were also categorized based on low or high baseline levels of plasma vitamin C, with the latter category showing the highest rate of loss per year of frozen storage in men (1.96 micromol/L, P value for difference <0.0001; percent loss 24.6%) and women (2.35 micromol/L, P value for difference <0.0001; percent loss 24.2%), as determined by multiple regression analysis adjusted for smoking status, age, and body mass index. In men, both baseline and final plasma vitamin C values were lower in smokers than never smokers, but for both men and women the rate of vitamin C loss during storage was not significantly different between smokers and never smokers. The results of this study show that vitamin C can be measured with reasonable reliability in plasma samples frozen for long periods of time without addition of any stabilizing agents.

Antioxidants↗
PubMed2002

Frequency of the WHO metabolic syndrome in European cohorts, and an alternative definition of an insulin resistance syndrome.

BACKGROUND: To describe the frequency, in some European populations, of the World Health Organisation (WHO) defined metabolic syndrome and to compare the frequency of this syndrome with an alternative definition for non-diabetic subjects, called the insulin resistance syndrome proposed by the European Group for the Study of Insulin Resistance (EGIR). METHODS: Investigators of eight European studies contributed, according to a written protocol, the frequencies of abnormalities of these two syndromes, by sex and age class, as well as the overall frequencies of the syndromes and the average number of abnormalities: 8200 men and 9363 women were included. RESULTS: The frequency of both syndromes increased with age and was almost always higher in men than women for a given age. In non-diabetic subjects the frequency of the WHO syndrome varied between 7% and 36% for men 40 to 55 years; for women of the same age, between 5% and 22%. The EGIR syndrome was less frequent than the WHO syndrome (1% to 22% in men, 1% to 14% in women 40-55 years), and in men this was mainly due to the differing definitions of central obesity, as the WHO definition included overall obesity, BMI > or = 30 kg/m(2). CONCLUSIONS: There is great variability in the frequency of the syndrome between different populations, due to the differing frequencies of the abnormalities and no doubt to the differing methodologies of measurement. Prospective studies and advances in the knowledge of physio-pathological mechanisms are required to determine the most appropriate and practical definition of the syndrome.

Cohort Studies↗