The Association between Proteomic Aging Clocks and the Risk of Cancer in Midlife Individuals.

Background: To measure the aging process before a cancer diagnosis, we developed the first cancer-specific proteomic aging clock (CaPAC) and examined its association with cancer risk in the Atherosclerosis Risk in Communities (ARIC) and Multi-Ethnic Study of Atherosclerosis (MESA) studies.

Methods: Using the SomaScan assay, ARIC measured 4,712 proteins in plasma samples collected in 1990-92 from 3,347 participants who developed cancer over follow-up until 2015 and 7,487 who remained cancer-free, all aged 46-70. We constructed CaPAC0 using elastic net regression among two-thirds randomly selected cancer-free participants (N=4,991, training set) and calculated age acceleration for CaPAC0 (CaPAA0) as residuals of CaPAC0 on chronological age in all remaining ARIC participants.

Functional variants in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with increased risk of colorectal cancer.

Background: Individuals with cystic fibrosis (CF; a recessive disorder) have an increased risk of colorectal cancer (CRC). Evidence suggests individuals with a single CFTR variant may also have increased CRC risk.

Methods: Using population-based studies (GECCO, CORECT, CCFR, and ARIC; 53 785 CRC cases and 58 010 controls), we tested for an association between the most common CFTR variant (Phe508del) and CRC risk.

Statin Use With Immune Checkpoint Inhibitors and Survival in Nonsmall Cell Lung Cancer.

Objective: To determine the association between concurrent statin use with immune checkpoint inhibitors (ICIs) and lung cancer-specific and overall mortality in patients with nonsmall cell lung cancer (NSCLC).

Materials And Methods: SEER-Medicare was used to conduct a retrospective study of Medicare beneficiaries ≥65 years of age diagnosed with NSCLC between 2007 and 2017 treated with an ICI. Patients were followed from date of first ICI claim until death, 1 month from last ICI claim, or 12/31/2018, whichever came first.

Alcohol consumption does not modify the polygenic risk score-based genetic risk of breast cancer in postmenopausal women: Atherosclerosis Risk in Communities study.

High genetic risk and alcohol consumption ≥1 drink/day are associated with increased breast cancer risk. However, the interaction between alcohol and genetics on breast cancer risk is poorly understood, including in populations not enriched with daily drinkers. We prospectively studied 5651 White and Black postmenopausal women in the Atherosclerosis Risk in Communities study.

Excess weight by degree and duration and cancer risk (ABACus2 consortium): a cohort study and individual participant data meta-analysis.

Background: Elevated body mass index (BMI) ≥25 kg/m is a major preventable cause of cancer. A single BMI measure does not capture the degree and duration of exposure to excess BMI. We investigate associations between adulthood overweight-years, incorporating exposure time to BMI ≥25 kg/m and cancer incidence, and compare this with single BMI.

Body mass index at birth and early life and colorectal cancer: A two-sample Mendelian randomization analysis in European and East Asian genetic similarity populations.

Background: Varying obesogenic inherited predisposition in early to later life may differentially impact colorectal cancer (CRC) development. Previous Mendelian randomization (MR) studies, conducted in populations of European genetic similarity, have not observed any significant associations between early life body weight with CRC risk. However, it remains unclear whether body mass index (BMI) at different early lifetime points is causally related with CRC risk in both Europeans and East Asian populations.

Survodutide for treatment of obesity: rationale and design of two randomized phase 3 clinical trials (SYNCHRONIZE™-1 and -2).

Objective: The objective of this study was to describe the rationale and design of two multinational phase 3 clinical trials of survodutide, an investigational glucagon and glucagon-like peptide-1 receptor dual agonist for the treatment of obesity with or without type 2 diabetes (T2D; SYNCHRONIZE-1 and -2).

Methods: In these ongoing double-blind trials, participants were randomized to once-weekly subcutaneous injections of survodutide or placebo added to lifestyle modification. Survodutide doses are uptitrated to 3.

Survodutide for the Treatment of Obesity: Rationale and Design of the SYNCHRONIZE Cardiovascular Outcomes Trial.

Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors may be more effective than GLP-1 receptor agonism alone in reducing body weight, but the cardiovascular (CV) effects are unknown. The authors describe the rationale and design of SYNCHRONIZE-CVOT, a phase 3, randomized, double-blind, parallel-group, event-driven, CV safety study of survodutide, a dual glucagon and GLP-1 receptor agonist, administered subcutaneously once weekly compared with placebo in adults with a body mass index ≥27 kg/m and established CV disease or chronic kidney disease, and/or at least 2 weight-related complications or risk factors for CV disease. The primary endpoint of SYNCHRONIZE-CVOT is time to first occurrence of the composite adjudicated endpoint of 5-point major adverse CV events.

The assessment, interpretation and implementation of lung ultrasound examinations in Heart Failure: Current evidence and gaps in knowledge.

Lung ultrasound (LUS) is a simple, fast and non-invasive tool for pulmonary congestion assessment with higher accuracy for the detection of acute heart failure (HF) compared to clinical examination and chest radiography. The integrated assessment with other ultrasound and echocardiographic parameters can lead to a better systemic and pulmonary congestion characterization. Additionally, the combination of echocardiographic and pulmonary features can identify patients at higher risk for adverse outcomes, potentially facilitating both acute and chronic HF management and prognostic stratification.

DNA Methylation-Derived Immune Cell Proportions and Cancer Risk in Black Participants.

This study describes associations between immune cell types and cancer risk in a Black population; elevated regulatory T-cell proportions that were associated with increased overall cancer and lung cancer risk, and elevated memory B-cell proportions that were associated with increased prostate and all cancer risk.

Development, characterization, and replication of proteomic aging clocks: Analysis of 2 population-based cohorts.

Background: Biological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in white individuals, and they used proteomic measures from only one-time point. In this study, we created de novo PACs and compared their performance to published PACs at 2 different time points in the Atherosclerosis Risk in Communities (ARIC) study of white and black participants (around 75% white and 25% black).

Subsequent risk of cancer among adults with peripheral artery disease in the community: The atherosclerosis risk in communities (ARIC) study.

Background And Aims: Several studies reported an increased cancer risk related to lower-extremity peripheral artery disease (PAD) but had important caveats: not accounting for key confounders like smoking, follow-up <10 years, or no race-specific results. To assess the long-term independent association of PAD with cancer incidence in a bi-racial community-based cohort.

Methods: We categorized 13,106 ARIC participants without cancer at baseline (mean age 54.

Association Between Obesity and Risk of Total and Obesity-Related Cancer in People With Incident Cardiovascular Disease.

Background: Cardiovascular disease (CVD) and cancer frequently co-occur due to shared risk factors such as obesity, which is linked to CVD and 14 cancer types. This study explores whether CVD pathophysiologies, combined with obesity, increase cancer risk, impacting clinical management.

Methods And Results: Data from the ARIC (Atherosclerosis Risk in Communities) study, spanning 28 years, were analyzed.

Validation of candidate protein biomarkers previously identified by genetic instruments for prostate cancer risk: A prospective cohort analysis of directly measured protein levels in the ARIC study.

Background: Multiple novel protein biomarkers have been shown to be associated with prostate cancer risk using genetic instruments. This study aimed to externally validate the associations of 30 genetically predicted candidate proteins with prostate cancer risk using aptamer-based levels in US Black and White men in the Atherosclerosis Risk in Communities (ARIC) study. Plasma protein levels were previously measured by SomaScan® using the blood collected in 1990-1992.

Blood Leukocyte DNA Methylation Markers of Periodontal Disease and Risk of Lung Cancer in a Case-Control Study Nested in the CLUE II Cohort.

Background: Periodontal disease and DNA methylation markers have separately been associated with lung cancer risk. Examining methylation levels at genomic regions previously linked to periodontal disease may provide insights on the link between periodontal disease and lung cancer.

Methods: In a nested case-control study drawn from the CLUE II cohort, we measured DNA methylation levels in 208 lung cancer cases and 208 controls.

Proteomic Aging Clocks and the Risk of Mortality among Longer-Term Cancer Survivors in the Atherosclerosis Risk in Communities (ARIC) Study.

Background: We constructed a new proteomic aging clock (PAC) and computed the published Lehallier's PAC to estimate biological age. We tested PACs' associations with mortality in longer-term cancer survivors and cancer-free participants.

Methods: ARIC measured 4,712 proteins using SomaScan in plasma samples collected at multiple visits, including Visit 5 (2011-13), from 806 cancer survivors and 3,699 cancer-free participants (aged 66-90).