Moving from two- to multi-way interactions among binary risk factors on the additive scale.

Many studies have focused on investigating deviations from additive interaction of two dichotomous risk factors on a binary outcome. There is, however, a gap in the literature with respect to interactions on the additive scale of >2 risk factors. In this paper, we present an approach for examining deviations from additive interaction among three or more binary exposures.

Correction: Chromatin structure, transcriptional activity and DNA repair efficiency affect the outcome of chemotherapy in multiple myeloma.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Lifestyle factors and risk of multimorbidity of cancer and cardiometabolic diseases: a multinational cohort study.

Background: Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases.

Methods: In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included.

Angiogenic and Antiangiogenic VEGFA Splice Variants in Colorectal Cancer: Prospective Retrospective Cohort Study in Patients Treated With Irinotecan-Based Chemotherapy and Bevacizumab.

Background: Alternative splicing of vascular endothelial growth factor A (VEGFA) results in VEGFAxxxb antiangiogenic isoforms that fail to activate angiogenesis. Bevacizumab, widely used in patients with metastatic colorectal cancer (CRC), binds both VEGFA and VEGFAxxxb isoforms.

Patients And Methods: Formalin-fixed, paraffin-embedded primary tumors from metastatic CRC patients treated with first-line FOLFIRI (leucovorin, 5-fluorouracil, irinotecan, and oxaliplatin) + bevacizumab (n = 285) or FOLFIRI only (n = 75) were collected.

The Impact of Cisplatin- or Non-Cisplatin-Containing Chemotherapy on Long-Term and Conditional Survival of Patients with Advanced Urinary Tract Cancer.

Background: The impact of cisplatin use on long-term survival of unselected patients with advanced urinary tract cancer (aUTC) has not been adequately investigated. We used a multinational database to study long-term survival and the impact of treatment type in unselected patients with aUTC.

Materials And Methods: A total of 1,333 patients with aUTC (cT4bN0M0, cTanyN+M0, cTanyNanyM+), transitional-cell, squamous, or adenocarcinoma histology who received systemic chemotherapy and had available survival data were selected.

Physical activity in breast cancer survivors: A systematic review and meta-analysis on overall and breast cancer survival.

Aim: To further quantify the association between physical activity (PA) after breast cancer diagnosis and all-cause mortality, breast cancer mortality and/or breast cancer recurrence.

Methods And Results: PubMed was searched until November 2017 for observational studies investigating any type of PA in association with total mortality, breast cancer mortality and/or breast cancer recurrence among women with breast cancer diagnosis. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using random-effects models for highest versus lowest categories of PA.

Adherence to the mediterranean diet and lymphoma risk in the european prospective investigation into cancer and nutrition.

There is a growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, no prospective study has yet investigated its influence on lymphoma. We evaluated the association between adherence to the MD and risk of lymphoma and its subtypes in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Gallstones and incident colorectal cancer in a large pan-European cohort study.

Gallstones, a common gastrointestinal condition, can lead to several digestive complications and can result in inflammation. Risk factors for gallstones include obesity, diabetes, smoking and physical inactivity, all of which are known risk factors for colorectal cancer (CRC), as is inflammation. However, it is unclear whether gallstones are a risk factor for CRC.

Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study.

Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.

Coffee and tea drinking in relation to the risk of differentiated thyroid carcinoma: results from the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

Purpose: Coffee and tea constituents have shown several anti-carcinogenic activities in cellular and animal studies, including against thyroid cancer (TC). However, epidemiological evidence is still limited and inconsistent. Therefore, we aimed to investigate this association in a large prospective study.

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.

Risk prediction for estrogen receptor-specific breast cancers in two large prospective cohorts.

Background: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction.

Methods: We built two models, for ER+ (Model) and ER- tumors (Model), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort.

Mediterranean diet and its components in relation to all-cause mortality: meta-analysis.

The beneficial association of the Mediterranean diet (MedDiet) with longevity has been consistently demonstrated, but the associations of MedDiet components have not been accordingly evaluated. We performed an updated meta-analysis of prospective cohort studies published up to 31 December 2017, to quantify the association of adherence to MedDiet, expressed as an index/score (MDS) and of its components with all-cause mortality. We estimated summary relative risks (SRR) and 95 % CI using random effects models.

Nutritional quality of food as represented by the FSAm-NPS nutrient profiling system underlying the Nutri-Score label and cancer risk in Europe: Results from the EPIC prospective cohort study.

Background: Helping consumers make healthier food choices is a key issue for the prevention of cancer and other diseases. In many countries, political authorities are considering the implementation of a simplified labelling system to reflect the nutritional quality of food products. The Nutri-Score, a five-colour nutrition label, is derived from the Nutrient Profiling System of the British Food Standards Agency (modified version) (FSAm-NPS).

Associations of angiogenesis-related proteins with specific prognostic factors, breast cancer subtypes and survival outcome in early-stage breast cancer patients. A Hellenic Cooperative Oncology Group (HeCOG) trial.

Several studies support an important role of angiogenesis in breast cancer growth and metastasis. The main objectives of the study were to investigate the immunohistochemical expression of vascular endothelial growth factor (VEGF) family ligands (VEGF-A and VEGF-C) and receptors (VEGFR1, VEGFR2 and VEGFR3) in breast cancer and their associations with clinicopathological parameters, cancer subtypes/subgroups and patient outcome. Formalin-fixed paraffin-embedded tumor tissue samples were collected from early-stage breast cancer patients treated with anthracycline-based chemotherapy within a randomized trial.

Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition.

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up.

Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort.

Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.

Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score.

Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies.

Objective: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts.

Design: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability).

Identifying and correcting epigenetics measurements for systematic sources of variation.

Background: Methylation measures quantified by microarray techniques can be affected by systematic variation due to the technical processing of samples, which may compromise the accuracy of the measurement process and contribute to bias the estimate of the association under investigation. The quantification of the contribution of the systematic source of variation is challenging in datasets characterized by hundreds of thousands of features.In this study, we introduce a method previously developed for the analysis of metabolomics data to evaluate the performance of existing normalizing techniques to correct for unwanted variation.

Dietary patterns in association to cancer incidence and survival: concept, current evidence, and suggestions for future research.

Assessing diet through dietary patterns has become popular in diet-disease investigations due to the appealing simplicity of expressing several dietary exposures through one variable. Current evidence suggests that there may exist a priori and a posteriori dietary patterns that are consistently associated with reduced all-cause, as well as site-specific cancer risk across different populations. Typical examples include the Mediterranean dietary pattern, the Healthy Eating Index, a number of "healthy" a posteriori dietary patterns, and others.

Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case-Control Study in EPIC.

The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites. Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls.

Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study.

Recent evidence suggested a weak relationship between alcohol consumption and pancreatic cancer (PC) risk. In our study, the association between lifetime and baseline alcohol intakes and the risk of PC was evaluated, including the type of alcoholic beverages and potential interaction with smoking. Within the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1,283 incident PC (57% women) were diagnosed from 476,106 cancer-free participants, followed up for 14 years.

Physical activity, mediating factors and risk of colon cancer: insights into adiposity and circulating biomarkers from the EPIC cohort.

Background: There is convincing evidence that high physical activity lowers the risk of colon cancer; however, the underlying biological mechanisms remain largely unknown. We aimed to determine the extent to which body fatness and biomarkers of various biologically plausible pathways account for the association between physical activity and colon cancer.

Methods: We conducted a nested case-control study in a cohort of 519 978 men and women aged 25 to 70 years followed from 1992 to 2003.

Prevalent somatic BRCA1 mutations shape clinically relevant genomic patterns of nasopharyngeal carcinoma in Southeast Europe.

Genomic patterns of nasopharyngeal carcinomas (NPCs) have as yet been studied in Southeast Asian (SEA) patients. Here, we investigated genomic patterns of locally advanced NPC Southeast European (SEE) patients treated with chemoradiotherapy. We examined 126 tumors (89% EBV positive) from Greek and Romanian NPC patients with massively parallel sequencing.