A randomized Phase I study of the safety, tolerability, pharmacokinetics and pharmacodynamics of BI 456906, a dual glucagon receptor/glucagon-like peptide-1 receptor agonist, in healthy Japanese men with overweight/obesity.

Aim: To report a Phase I study of subcutaneous glucagon receptor (GCGR)/glucagon-like peptide-1 receptor (GLP-1R) dual agonist BI 456906 versus placebo in healthy Japanese men with overweight/obesity.

Materials And Methods: We investigated multiple rising doses of BI 456906 escalated over 16 weeks (maximum doses: 1.8 mg once weekly [dose group {DG} 1], 4.

Variation of Positive Predictive Values of Fecal Immunochemical Tests by Polygenic Risk Score in a Large Screening Cohort.

Introduction: Prevalence of colorectal neoplasms varies by polygenic risk scores (PRS). We aimed to assess to what extent a PRS might be relevant for defining personalized cutoff values for fecal immunochemical tests (FITs) in colorectal cancer screening.

Methods: Among 5,306 participants of screening colonoscopy who provided a stool sample for a quantitative FIT (Ridascreen Hemoglobin or FOB Gold) before colonoscopy, a PRS was determined, based on the number of risk alleles in 140 single nucleotide polymorphisms.

Associations between Genetic Variants and Blood Biomarkers of One-Carbon Metabolism in Postmenopausal Women from the Women's Health Initiative Observational Study.

Background: Genetic variation in one-carbon metabolism may affect nutrient concentrations and biological functions. However, data on genetic variants associated with blood biomarkers of one-carbon metabolism in US postmenopausal women are limited, and whether these associations were affected by the nationwide folic acid (FA) fortification program is unclear.

Objectives: We investigated associations between genetic variants and biomarkers of one-carbon metabolism using data from the Women's Health Initiative Observational Study.

Decreasing resection rates for nonmetastatic gastric cancer in Europe and the United States.

Background: Resection is the cornerstone of curative treatment for many nonmetastatic gastric cancers (GCs), but the population treatment patterns remains largely unknown. This large international population-based study aimed at investigating the treatment patterns and trends for nonmetastatic GC in Europe and the United States and at exploring factors associated with resection.

Methods: Data of patients with microscopically confirmed primary invasive GC without distant metastasis from the national cancer registries of the Netherlands, Belgium, Sweden, Norway, Slovenia, and Estonia and the US Surveillance, Epidemiology, and End Results (SEER)-18 Program were retrieved.

Polymorphisms in the Angiogenesis-Related Genes , and Are Associated with Survival of Colorectal Cancer Patients.

An individual's inherited genetic variation may contribute to the 'angiogenic switch', which is essential for blood supply and tumor growth of microscopic and macroscopic tumors. Polymorphisms in angiogenesis-related genes potentially predispose to colorectal cancer (CRC) or affect the survival of CRC patients. We investigated the association of 392 single nucleotide polymorphisms (SNPs) in 33 angiogenesis-related genes with CRC risk and survival of CRC patients in 1754 CRC cases and 1781 healthy controls within DACHS (Darmkrebs: Chancen der Verhütung durch Screening), a German population-based case-control study.

Risk-Adapted Cutoffs in Colorectal Cancer Screening by Fecal Immunochemical Tests.

Introduction: Fecal immunochemical tests (FITs) for hemoglobin are increasingly used in colorectal cancer (CRC) screening. The use of uniform positivity thresholds (cutoffs) within screening populations is expected to imply lower positive predictive values (PPVs) and higher numbers of colonoscopies needed (numbers needed to scope [NNSs]) to detect advanced neoplasms among screening participants at lower risk compared with those at higher risk. We aimed to assess such variation and its potential implications in a large screening cohort.

Stage-Specific Sensitivity of Fecal Immunochemical Tests for Detecting Colorectal Cancer: Systematic Review and Meta-Analysis.

Objective: Fecal immunochemical tests (FITs) detect the majority of colorectal cancers (CRCs), but evidence for variation in sensitivity according to the CRC stage is sparse and has not yet been systematically synthesized. Thus, our objective was to systematically review and summarize evidence on the stage-specific sensitivity of FITs.

Methods: We screened PubMed, Web of Science, Embase, and the Cochrane Library from inception to June 14, 2019, for English-language articles reporting on the stage-specific sensitivity of FIT for CRC detection using colonoscopy as a reference standard.

Head-to-Head Comparison of the Performance of 17 Risk Models for Predicting Presence of Advanced Neoplasms in Colorectal Cancer Screening.

Objectives: Many risk scores have been proposed to predict presence of advanced colorectal neoplasms, but a comprehensive comparison conducted in the same population is sparse. The aim of this study was to evaluate and directly compare the diagnostic performance of published risk prediction models for advanced colorectal neoplasms.

Methods: Data were drawn from 2 cohorts of subjects undergoing screening colonoscopy in Germany, i.

A snapshot of current genetic testing practice in Lynch syndrome: The results of a representative survey of 33 Latin American existing centres/registries.

We aimed to assess the current genetics practice to manage patients with Lynch syndrome (LS) across Latin America. A Latin American LS survey was sent out to 52 centres/registries, comprising a total of 12 countries from the region. Overall, 33 centres completed the survey, of which the oldest LS registry was established in 1992 in Sao Paulo (Brazil), and the youngest this year in San Jose (Costa Rica).

Significance of Examined Lymph Node Number in Accurate Staging and Long-term Survival in Resected Stage I-II Pancreatic Cancer-More is Better? A Large International Population-based Cohort Study.

Objective: This large international cohort study aimed to investigate the associations of examined lymph node (ELN) number with accurate staging and long-term survival in pancreatic adenocarcinoma (PaC) and to robustly determine the minimal and optimal ELN thresholds.

Summary Background Data: ELN number is an important quality metric in cancer care. The recommended minimal ELN number in PaC to accurately stage cancer varies greatly across guidelines, and the optimal number especially to adequately stratify patient survival has not yet been established.

Development and validation of a prognostic model to predict the prognosis of patients who underwent chemotherapy and resection of pancreatic adenocarcinoma: a large international population-based cohort study.

Background: Pancreatic cancer (PaC) remains extremely lethal worldwide even after resection. PaC resection rates are low, making prognostic studies in resected PaC difficult. This large international population-based study aimed at exploring factors associated with survival in patients with resected TNM stage I-II PaC receiving chemotherapy and at developing and internationally validating a survival-predicting model.

Performance of individual and joint risk stratification by an environmental risk score and a genetic risk score in a colorectal cancer screening setting.

Early detection of colorectal neoplasms can reduce the disease burden of colorectal cancer by timely intervention of individuals at high risk. Our aim was to evaluate a joint environmental-genetic risk score as a risk stratification tool for early detection of advanced colorectal neoplasm (ACRN). Known environmental risk factors and high-risk genetic loci were summarized into risk scores for ACRN in 1014 eligible participants of a screening study.

Fibroblast growth factor 21 as a circulating biomarker at various stages of colorectal carcinogenesis.

Background: Despite evidence that inflammation and metabolism play a crucial role in colorectal carcinogenesis, there have been few studies on the association of inflammatory and metabolic protein biomarkers in various stages of colorectal carcinogenesis.

Methods: Ninety-two inflammatory and metabolic biomarkers were measured in plasma samples of participants of screening colonoscopy. Markers identified to be significantly associated with the presence of advanced colorectal neoplasia (ACN) in a discovery set (n = 204) were validated in an independent replication set (n = 422).

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence.

Stratified survival of resected and overall pancreatic cancer patients in Europe and the USA in the early twenty-first century: a large, international population-based study.

Background: The prognosis of pancreatic cancer (PaC) strongly varies across different stages and age groups, which has unfortunately not been well recorded in the literature. This international population-based study aimed to provide tumor-node-metastasis (TNM) stage- and age-specific survival estimates and trends in resected and overall (resected and unresected) PaC in the early twenty-first century.

Methods: Using data from the US Surveillance, Epidemiology, and End Results-18 Program and the national cancer registries of the Netherlands, Belgium, Norway, and Slovenia, short-term and long-term overall survival results stratified by TNM stage and age in resected and overall primary PaC, irrespective of being microscopically confirmed or not, in 2003-2014 were computed using the Kaplan-Meier method.

Biomarker discovery study of inflammatory proteins for colorectal cancer early detection demonstrated importance of screening setting validation.

Objectives: Most studies identifying inflammatory markers for early detection of colorectal cancer (CRC) were conducted using clinically manifest cases. We aimed to identify circulating inflammatory biomarkers for early detection of CRC and validate them in both a clinical setting and a true screening setting.

Study Design And Setting: A total of 92 inflammatory proteins were quantified in baseline plasma samples from individuals clinically diagnosed with CRC and neoplasm-free controls matched on age and sex (training set).

Nonsurgical therapies for resected and unresected pancreatic cancer in Europe and USA in 2003-2014: a large international population-based study.

The role of chemotherapy in the treatment of pancreatic cancer (PaC) has been well-established, while radiation plays ambiguous roles. This international large-scale population-based study aimed to investigate the real-world application of chemotherapy and radiotherapy for resected and unresected PaC in Europe and USA. Population-based data from multiple European national cancer registries and the US Surveillance, Epidemiology and End Results (SEER)-18 database during 2003-2014 were analyzed.

Pathway analysis of genetic variants in folate-mediated one-carbon metabolism-related genes and survival in a prospectively followed cohort of colorectal cancer patients.

Folate-mediated one-carbon metabolism (FOCM) is a key pathway essential for nucleotide synthesis, DNA methylation, and repair. This pathway is a critical target for 5-fluorouracil (5-FU), which is predominantly used for colorectal cancer (CRC) treatment. A comprehensive assessment of polymorphisms in FOCM-related genes and their association with prognosis has not yet been performed.

Robust prediction of gene regulation in colorectal cancer tissues from DNA methylation profiles.

DNA methylation is recognized as one of several epigenetic regulators of gene expression and as potential driver of carcinogenesis through gene-silencing of tumor suppressors and activation of oncogenes. However, abnormal methylation, even of promoter regions, does not necessarily alter gene expression levels, especially if the gene is already silenced, leaving the exact mechanisms of methylation unanswered. Using a large cohort of matching DNA methylation and gene expression samples of colorectal cancer (CRC; n = 77) and normal adjacent mucosa tissues (n = 108), we investigated the regulatory role of methylation on gene expression.

Genetic Risk Score Is Associated With Prevalence of Advanced Neoplasms in a Colorectal Cancer Screening Population.

Background & Aims: The presence of specific single nucleotide polymorphisms (SNPs) can be used to calculate an individual's risk for colorectal cancer (CRC), called a genetic risk score (GRS). We investigated whether GRS can identify individuals with clinically relevant neoplasms in a screening colonoscopy population.

Methods: We derived a GRS based on 48 SNPs associated with CRC, identified in a comprehensive literature search.

Administration of adjuvant chemotherapy for stage II-III colon cancer patients: An European population-based study.

The advantage of adjuvant chemotherapy (ACT) for treating Stage III colon cancer patients is well established and widely accepted. However, many patients with Stage III colon cancer do not receive ACT. Moreover, there are controversies around the effectiveness of ACT for Stage II patients.

Resection of pancreatic cancer in Europe and USA: an international large-scale study highlighting large variations.

Objective: Resection can potentially cure resectable pancreatic cancer (PaC) and significantly prolong survival in some patients. This large-scale international study aimed to investigate variations in resection for PaC in Europe and USA and determinants for its utilisation.

Design: Data from six European population-based cancer registries and the US Surveillance, Epidemiology, and End Results Program database during 2003-2016 were analysed.

Neoadjuvant Therapy in Rectal Cancer Patients With Clinical Stage II to III Across European Countries: Variations and Outcomes.

Background: Neoadjuvant therapy improves survival of patients with clinical stage II and III rectal cancer in clinical trials. In this study, we investigated the administration of neoadjuvant radiotherapy (neo-RT) and neoadjuvant chemoradiotherapy (neo-CRT) and its association with survival in resected patients in 2 European countries (The Netherlands and Sweden) and at 3 specialist centers.

Materials And Methods: Administration of neoadjuvant treatment (all registries) and overall survival after surgery in The Netherlands and Sweden were assessed.

Fusobacterium and colorectal cancer: causal factor or passenger? Results from a large colorectal cancer screening study.

Colorectal cancer is a leading cause of morbidity and mortality worldwide in both men and women. The gut microbiome is increasingly recognized as having an important role in human health and disease. Fusobacterium has been identified in former studies as a leading gut bacterium associated with colorectal cancer, but it is still not clear if it plays an oncogenic role.