Circulating fatty acid binding protein 4 (FABP-4) concentrations and mortality in individuals with colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study.

Human fatty acid binding protein-4 (FABP-4), a protein elevated in obesity that promotes colon cancer cell invasiveness and metastasis, may be associated with higher mortality in individuals with colorectal cancer (CRC) and may serve as a mediator of the obesity-mortality association in these individuals. We used a causal diagram to inform covariate selection and applied Cox proportional hazards models to estimate hazard ratios (HRs) for CRC-specific, non-CRC-specific, and all-cause mortality by FABP-4 levels measured in baseline blood samples from 1371 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. Competing risk analyses were adapted for CRC and non-CRC deaths.

Thyroid hormones and epithelial ovarian cancer risk and survival: results from the EPIC study.

Background: Thyroid-stimulating hormone (TSH) and thyroid hormones (free triiodothyronine[fT3] and free thyroxine[fT4]) may influence cancer outcomes, but evidence for ovarian cancer is limited.

Methods: We conducted a nested case-control study comparing 578 epithelial ovarian cancer (EOC) cases to matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). To examine associations between circulating TSH, fT3, and fT4 levels and EOC risk, we estimated risk ratios (RRs) and 95% confidence intervals (CIs) per standard deviation (SD) using conditional logistic regression.

Recommendations for validating omics prediction models: Insights from a lung cancer RNA biomarker study.

Background: External validation of predictive models in medical research is crucial to ensure their generalizability and applicability across diverse populations. However, validation often reveals discrepancies in model performance due to cohort differences, sample collection and storage, overfitting, and inconsistencies in data handling. This study investigates the challenges encountered during external validation of predictive models for early lung cancer detection using small RNA biomarkers, tying these challenges to specific validation outcomes and deriving recommendations.

Statins and the risk of gynecological cancer: a Norwegian population-based cohort study.

Background: Endometrial, ovarian, and cervical cancers are the most common gynecological cancers, with 1.4 million diagnoses worldwide in 2022. Statins are widely used for cardiovascular conditions and have been studied for their association with gynecological cancer risk, but results to date have been inconclusive.

Can serum metabolic signatures inform on the relationship between healthy lifestyle and colon cancer risk?

Background: Colon cancer is strongly influenced by lifestyle factors. Sociodemographic factors like sex and socioeconomic position (SEP) might modulate the relationship between lifestyle and colon cancer risk. Metabolomics offers potential to uncover biological mechanisms linking lifestyle and colon cancer.

Low-dose aspirin and non-aspirin non-steroidal anti-inflammatory drugs and epithelial ovarian cancer survival: a registry-based cohort study in Norway.

Background: Aspirin and non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAID) have been associated with improved survival in individuals with epithelial ovarian cancer (EOC); however, findings to date are inconsistent.

Methods: We conducted a registry-based cohort study evaluating survival following an incident invasive EOC diagnosis including individuals diagnosed between 2004-2018 (n = 4325; n = 2206 deaths; n = 1973 EOC deaths). Evaluated exposures were low-dose aspirin and NA-NSAIDs.

Ovarian cancer survival by residual disease following cytoreductive surgery: a nationwide study in Norway.

Background: Residual disease (RD) following cytoreductive surgery is prognostic for epithelial ovarian cancer (EOC) patients. Few studies have evaluated RD and survival by tumor histotype and across continuous RD diameter.

Methods: 2608 individuals with stages III-IV invasive EOC diagnosed between 2013 and 2022 were identified using the Cancer Registry of Norway.

A Prospective Study Consortium for the Discovery and Validation of Early Detection Markers for Ovarian Cancer - Baseline Findings for CA125.

Purpose: Epithelial ovarian cancer (EOC) is a lethal malignancy. Cancer antigen 125 (CA125), the "best" available marker for detecting EOC, has insufficient sensitivity and specificity for earlier-stage disease and is not a meaningful screening tool, motivating the search for further biomarkers. Cancer biomarker discovery is enhanced by "omics" technologies.

Prospective evaluation of 92 protein biomarkers for early detection of endometrial cancer.

The human epididymis protein 4 (HE4) remains the best available endometrial cancer (EC) biomarker; however, its discrimination between cases and cancer-free individuals is limited and might be improved when combined with other protein markers. We evaluated the discrimination capacity of 92 proteins as potential early detection biomarkers for EC in nested case-control studies in the European Prospective Investigation into Cancer and Nutrition (EPIC) (63 cases, 123 controls) and Janus (75 cases, 146 controls) cohorts, evaluating blood samples taken ≤2 years prior to diagnosis. Proteins were measured with the Olink Target 96 Oncology II panel assays.

Education level and risk of breast cancer by tumor subtype in the EPIC cohort.

Breast cancer (BC) is a heterogeneous disease with subtypes based on receptor status (estrogen receptor [ER], progesterone receptor [PR], and human epidermal growth factor receptor 2 [HER2]), influencing prognosis and treatment. A higher socioeconomic position (SEP) is associated with an increased BC risk, but its relation to BC subtypes is less clear. This study analyzed 311,631 women from the EPIC cohort, focusing on the incidence of in situ and invasive BC (overall and by receptor status and subtype).

Reproductive Factors, Sex Hormone Levels, and Differentiated Thyroid Cancer Risk: A Mendelian Randomization Study.

Differentiated thyroid carcinoma (DTC) is occurring three times more frequently in females than in males. However, the underlying biological mechanisms driving this discrepancy remain poorly understood. To investigate the causal role of sex hormones and reproductive factors in the risk of DTC, we implemented a two-sample Mendelian randomization (MR) analysis.

Non-steroidal anti-inflammatory medication use and endometrial cancer survival: A population-based Norwegian cohort study.

While nonsteroidal anti-inflammatory drugs (NSAIDs) have been shown to improve survival in certain cancers, data in patients with endometrial cancer (EC) is conflicting. This study investigated use of aspirin and nonaspirin NSAIDs (NA-NSAIDs) and EC-specific-and all-cause death. This nationwide cohort study linked data from the Cancer Registry of Norway with The Norwegian Prescription database.

Exome sequencing identifies HELB as a novel susceptibility gene for non-mucinous, non-high-grade-serous epithelial ovarian cancer.

Rare, germline loss-of-function variants in a handful of DNA repair genes are associated with epithelial ovarian cancer. The aim of this study was to evaluate the role of rare, coding, loss-of-function variants across the genome in epithelial ovarian cancer. We carried out a gene-by-gene burden test with various histotypes using data from 2573 non-mucinous cases and 13,923 controls.

Identifying Metabolomic Mediators of the Physical Activity and Colorectal Cancer Relationship.

Background: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer. However, the mediating role of the circulating metabolome in this relationship remains unclear.

Methods: Targeted metabolomics data from 6,055 participants in the European Prospective Investigation into Cancer and Nutrition cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels.

Beta-blockers and epithelial ovarian cancer survival: A Norwegian population-based cohort study.

Cancer diagnosis and therapy cause stress to the body. Preclinical studies have shown that stress hormones can stimulate tumor progression and metastasis by interacting with β-adrenergic receptors, and that β-blockers can inhibit those processes. We assessed if β-blocker use was associated with survival in a nationwide cohort of women with epithelial ovarian cancer (EOC).

Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.

BACKGROUNDDespite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive 10 or more years after standard treatment.METHODSWe evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared with mid-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.

Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses.

Background: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear.

Methods: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons.

Differential levels of circulating RNAs prior to endometrial cancer diagnosis.

Endometrial cancer (EC) is one of the most common female cancers and there is currently no routine screening strategy for early detection. An altered abundance of circulating microRNAs (miRNAs) and other RNA classes have the potential as early cancer biomarkers. We analyzed circulating RNA levels using small RNA sequencing, targeting RNAs in the size range of 17-47 nucleotides, in EC patients with samples collected prior to diagnosis compared to cancer-free controls.

Endogenous estrogen receptor modulating oxysterols and breast cancer prognosis: Results from the MARIE patient cohort.

Background: 27-hydroxycholesterol (HC) and 25-HC were identified as endogenous selective estrogen receptor modulators (SERMs) and estrogen receptor (ER) modulators, respectively. They are hypothesized to play a role in multiple physiologic processes and pathologies, including breast cancer development and progression.

Methods: We evaluated circulating 27-HC and 25-HC, and outcomes following a breast cancer diagnosis in 2282 women from the MARIE study over median follow-up of 11.

Characterization of ovarian cancer survival by histotype and stage: A nationwide study in Norway.

Contemporary population-based data on ovarian cancer survival using current subtype classifications and by surgical status are sparse. We evaluated 1-, 3-, 5- and 7-year relative (and overall) survival, and excess hazards in patients with borderline tumors or invasive epithelial ovarian cancer diagnosed 2012 to 2021 in a nationwide registry-based cohort in Norway. Outcomes were evaluated by histotype, FIGO stage, cytoreduction surgery and residual disease.

Physical activity and breast cancer survival: results from the Nurses' Health Studies.

Background: Physical activity is generally associated with better outcomes following diagnosis; however, few studies have evaluated change in pre- to postdiagnosis activity and repeated measures of activity by intensity and type.

Methods: We evaluated physical activity and survival following a breast cancer diagnosis in the Nurses' Health Study and Nurses' Health Study II (n = 9308 women, n = 1973 deaths). Physical activity was evaluated as updated cumulative average of metabolic equivalent of task (MET)-h/wk (assigned per activity based on duration and intensity) and change in pre- to postdiagnosis activity.

Association of circulating free and total oxysterols in breast cancer patients.

Objectives: Oxysterols, a family of oxidized cholesterol derivates, are of increasing interest due to their role in cancer development and progression. Some oxysterols are estrogen receptor modulators and thus of particular interest in breast cancer research. In human studies, two forms of circulating oxysterols are commonly evaluated: "free" (unesterified) and "total" (esterified and unesterified).