Claudia Agnoli

• Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

OBJECTIVE To examine separate and joint associations between pre-existing cardiometabolic comorbidities and all cause and cause specific mortality in adults with cancer. DESIGN Multinational cohort study. SETTING Seven European countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, 1 January 1992 to 31 Decemb...

Industrial food processing has been linked to various health outcomes including cancer. To examine associations between the degree of food processing and risk of colorectal cancer (CRC) and its sub‐sites, data from the European Prospective Investigation into Cancer (EPIC) including 6155 incident CRC cases (n = 450,111 participants), were analyzed....

Importance Adherence to the Mediterranean Diet (MedDiet) has been associated with a lower incidence of cancer and reduced weight gain. These associations suggest a potential role for the MedDiet in lowering the risk of obesity-related cancers (ORCs). Obesity is a known risk factor for various cancers and shows an inverse association with MedDiet ad...

Introduction Breast cancer is the most common cancer among women, and metabolic syndrome (MetS) is a risk factor for breast cancer, especially postmenopausal breast cancer. We evaluated the role of the advanced glycated end products (AGEs) levels contributing to the association between MetS and breast cancer risk. Methods Plasma AGEs were measured...

Introduction Observational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such a relationship is causal. This study used genetic instruments for education to estimate the effect of education on T2D using the Mendelian ran...

Background and Objective: Nutrimetabolomics may reveal novel insights into early metabolic alterations and the role of dietary exposures on prostate cancer (PCa) risk. We aimed to prospectively investigate the associations between plasma metabolite concentrations and PCa risk, including clinically relevant tumor subtypes. Methods: We used a targete...

Measuring pre‐diagnostic blood metabolites may help identify novel risk factors for prostate cancer. Using data from 4387 matched case–control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we investigated the associations of 148 individual metabolites and three previously defined metabolite patterns with...

Background Associations of saturated and unsaturated fatty acids (FAs) with cardiovascular disease (CVD) remain controversial. We therefore aimed to investigate the prospective associations of objectively measured FAs with CVD, including incident coronary heart disease (CHD) and stroke, as well as CVD mortality. Methods Circulating FA concentratio...

Background Inflammation influences tumour progression and cancer prognosis, but its role preceding breast cancer (BC) and its prognostic implications remain inconclusive. Methods We studied pre-diagnostic plasma inflammatory biomarkers in 1538 women with BC from the EPIC study. Cox proportional hazards models assessed their relationship with all-c...

Background Adiposity has been characterised as a modifiable risk factor of prostate cancer. Its association with outcomes after prostate cancer diagnosis, however, needs to be better understood and obtain more evidence to assist the development of lifestyle guidance for prostate cancer patients. Methods We investigated the associations between adi...

Background: Diet plays an important role in the development of cardiovascular diseases and in maintaining sustainable planetary boundaries. The EAT-Lancet Planetary Health Diet could potentially provide co-benefits for human and environmental health, yet evidence on the association between adherence to the EAT-Lancet Planetary Health Diet and risk...

Background Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are implicated in the aetiology of non-communicable diseases. Our study aimed to evaluate associations between NAFLD and MetS with overall and cause-specific mortality. Methods We used dietary, lifestyle, anthropometric and metabolic biomarker data from a random sub...

Background The mechanisms underlying alcohol‐induced breast carcinogenesis are not fully understood but may involve hormonal changes. Methods Cross‐sectional associations were investigated between self‐reported alcohol intake and serum or plasma concentrations of estradiol, estrone, progesterone (in premenopausal women only), testosterone, androst...

Breast cancer (BC) is the most common cancer in women, with 2.3 million diagnoses in 2020. There is growing evidence that lifestyle factors, including dietary factors, particularly the complex interactions and synergies between different foods and nutrients (and not a single nutrient or food), may be associated with a higher risk of BC. The aim of...

Background Altered lipid metabolism is a hallmark of cancer development. However, the role of specific lipid metabolites in colorectal cancer development is uncertain. Methods In a case–control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined associations between pre-diagnostic circulating co...

Background: Tobacco consumption, incorrect nutrition and insufficient physical activity/sedentariness represent modifiable NCDs risk factors in Western countries. To evaluate recent lifestyle indicators in Italy, data from the national Health Examination Survey (HES), implemented in 2018–2019 within the CUORE Project, were assessed. Methods: Age–se...

Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre‐diagnostic serum resistin concentrations in relation to CRC‐specific and all‐cause morta...

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption...

Purpose To investigate the role of adiposity in the associations between ultra-processed food (UPF) consumption and head and neck cancer (HNC) and oesophageal adenocarcinoma (OAC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Methods Our study included 450,111 EPIC participants. We used Cox regressions to inves...

Mild Cognitive Impairment (MCI) may be a prodromal condition of clinically overt dementia. Several risk factors have been investigated for their possible role in dementia etiology. Among these, higher adherence to healthy dietary habits, such as the Mediterranean-type diets, has been hypothesized to decrease dementia risk. Our objective was to stud...

Background The mechanisms underlying alcohol-induced breast carcinogenesis are not fully understood but may involve hormonal changes. Methods We investigated cross-sectional associations between self-reported alcohol intake and serum or plasma concentrations of oestradiol, oestrone, progesterone (in pre-menopausal women only), testosterone, andros...

Purpose The incidence of small intestinal cancer (SIC) is increasing, however, its aetiology remains unclear due to a lack of data from large-scale prospective cohorts. We examined modifiable risk factors in relation to SIC overall and by histological subtype. Methods We analysed 450,107 participants enrolled in the European Prospective Investigat...

Background: Since the first version of the dietary inflammatory index (DII®) developed in the past decade, several other versions have been developed. However, to date no study has attempted to compare these versions with respect to their associations with biomarkers of inflammation. Objective: We aimed to investigate the relationship between fo...

Background Self-reported adherence to the Mediterranean diet has been modestly inversely associated with incidence of type 2 diabetes (T2D) in cohort studies. There is uncertainty about the validity and magnitude of this association due to subjective reporting of diet. The association has not been evaluated using an objectively measured biomarker o...

Aims: A comprehensive review comparing the effect of vegetarian (V) and non-vegetarian (NV) diets on the major cardiometabolic diseases' outcomes was performed. Data synthesis: We performed literature research (up to December 31, 2022) of the evidence separately for vascular disease (VD), obesity (OB), dyslipidemia (Dysl), hypertension (HPT), ty...

Evidence linking body fatness to breast cancer (BC) prognosis is limited. While it seems that excess adiposity is associated with poorer BC survival, there is uncertainty over whether weight changes reduce mortality. This study aimed to assess the association between body fatness and weight changes pre-and postdiagnosis and overall mortality and BC...

Breast cancer (BC) is a multifactorial disease caused by an interaction between genetic predisposition and environmental exposures. MicroRNAs are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and seem to be related to cancer risk factors. We conducted a systematic review and meta-...

Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European...

Malignant pleural mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed to identify a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. In a case-control study nested in the European Prospective Investigation into Cancer and Nutrition...

Polyphenols are bioactive compounds from plants with antioxidant properties that may have a protective role against body weight gain, with adipose tissue and systemic oxidative stress as potential targets. We aimed to investigate the dietary intake of individual polyphenols and their association with 5-year body weight change in a sub-cohort of the...

Introduction: In this paper, an analytical pipeline designed for untargeted lipidomic profiling in human plasma is proposed. The analytical pipeline was developed for case-control studies nested in prospective cohorts. Methods: The procedure consisted of isopropanol protein precipitation followed by reverse phase liquid chromatography coupled to...

Colorectal cancer (CRC) is one of the most common cancers worldwide. Primary and secondary preventions are key to reducing the global burden. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and to be related to cancer risk factors, such as obesity and inflamma...

Diet has long been identified as a major determinant of cardiovascular and other chronic diseases. In this study, we assess the relation between adherence to different dietary patterns and biochemical and metabolic parameters as well as the 10-year risk of major cardiovascular diseases (CVDs) in a community of blood donors in Northern Italy. We ass...

Purpose There is existing evidence on the potential role of chronic inflammation in the pathogenesis of pancreatic cancer (PC) and on how risk may be modulated by dietary factors. Pro-inflammatory diets are suggested to be associated with increased risk of PC but, so far, evidence remains not conclusive. We examined the association between the diet...

Background. Malignant Pleural Mesothelioma (MPM) is an aggressive cancer with a dismal prognosis. Early therapeutic interventions could improve patient outcomes. We aimed at identifying a pattern of microRNAs (miRNAs) as potential early non-invasive markers of MPM. Methods. In a case–control study nested in the European Prospective Investigation in...

We prospectively investigated the associations of protein intake with colorectal cancer (CRC) risk in middle-aged Italian men and women. Food consumption was assessed by validated Epic semiquantitative food-frequency questionnaires. Multivariable Cox models stratified by center, age, and sex, adjusted for confounders, estimated the associations of...

Purpose Chronic inflammation is thought to initiate or promote differentiated thyroid cancer (DTC) and previous studies have shown that diet can modulate this inflammatory process. We aimed to evaluate the association of several dietary scores reflecting the inflammatory potential of the diet with DTC risk. Methods Within the EPIC cohort, 450,063...

Previous studies have suggested that components of one‐carbon metabolism, particularly circulating vitamin B6, have an etiological role in renal cell carcinoma (RCC). Vitamin B6 is a cofactor in the transsulfuration pathway. We sought to holistically investigate the role of the transsulfuration pathway in RCC risk. We conducted a nested case‐contro...

Aims: This study aimed to evaluate the association between physical activity and the incidence of coronary heart disease (CHD) in individuals with and without CHD risk factors. Methods and results: EPIC-CVD is a case-cohort study of 29 333 participants that included 13 582 incident CHD cases and a randomly selected sub-cohort nested within the Eur...

Background: Case-control studies show that copper (Cu) is high and zinc (Zn) low in blood and urine of breast cancer (BC) women compared to controls. Methods: To assess whether pre-diagnostic Cu and Zn are associated with BC risk, odds ratios (OR) of BC according to Cu, Zn, and Cu/Zn ratio in plasma and urine were estimated in a nested case-cont...

BACKGROUND To examine the associations of animal and plant protein intake with all-cause, cardiovascular and cancer mortality risk in middle-aged Italian men and women with substantially lower animal protein intake than North Americans. METHODS AND RESULTS Food consumption was assessed by validated Epic semiquantitative FFQs. Multivariable Cox mod...

Background: Endogenous sex hormones may contribute to higher colorectal cancer incidence rates in men compared to women, but despite an increased number of studies, clear evidence is lacking. Methods: We conducted a comprehensive nested case-control study of circulating concentrations of sex hormones, sex hormone precursors and sex hormone bindi...

Background: Here, we explore the association between excess weight during early to mid-adulthood and survival in patients diagnosed with breast and colorectal cancer, using a pooled analysis of five cohort studies and study participants from 11 countries. Methods: Participant-level BMI trajectories were estimated by fitting a growth curve model...

A higher selenium (Se) status has been shown to be associated with lower risk for colorectal cancer (CRC), but the importance of Se in survival after CRC diagnosis is not well studied. The associations of prediagnostic circulating Se status (as indicated by serum Se and selenoprotein P (SELENOP) measurements) with overall and CRC-specific mortality...

Background Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting t...

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sam...

Pooling metabolomics data across studies is often desirable to increase the statistical power of the analysis. However, this can raise methodological challenges as several preanalytical and analytical factors could introduce differences in measured concentrations and variability between datasets. Specifically, different studies may use variable sam...

Context In a previous study we reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies. Objective Assess whether risk factors for breast cancer are correlates of AMH concentration Design Cross-sectional Participants 3831 healthy premenopausal women (...

Background Endometrial cancer is strongly associated with obesity and dysregulation of metabolic factors such as estrogen and insulin signaling are causal risk factors for this malignancy. To identify additional novel metabolic pathways associated with endometrial cancer we performed metabolomic analyses on pre-diagnostic plasma samples from 853 ca...

Epidemiologic studies examining the association between specific fatty acids and colorectal cancer (CRC) risk are inconclusive. We investigated the association between dietary estimates and plasma levels of individual and total saturated (SFA), monounsaturated (MUFA), industrial‐processed trans (iTFA), and ruminant‐sourced trans (rTFA) fatty acids,...

Background The mechanisms underlying the obesity-cancer relationship are incompletely understood. This study aimed to characterise metabolic signatures of greater body size and to investigate their association with two obesity-related malignancies, endometrial and colorectal cancers, and with weight loss within the context of an intervention study....

Background & aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures...

Increasing evidence points to a role for inflammation in lung carcinogenesis. A small number of circulating inflammatory proteins have been identified as showing elevated levels prior to lung cancer diagnosis, indicating the potential for prospective circulating protein concentration as a marker of early carcinogenesis. To identify novel markers of...

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospecti...

To better understand the role of individual and lifestyle factors in human disease, an exposome‐wide association study was performed to investigate within a single‐study anthropometry measures and lifestyle factors previously associated with B‐cell lymphoma (BCL). Within the European Prospective Investigation into Cancer and nutrition study, 2402 i...

Objective: To determine if the Food Standards Agency nutrient profiling system (FSAm-NPS), which grades the nutritional quality of food products and is used to derive the Nutri-Score front-of-packet label to guide consumers towards healthier food choices, is associated with mortality. Design: Population based cohort study. Setting: European Pr...

Background & Aims The overall macronutrient composition of diet, rather than just calorie intake, may influence long-term changes of anthropometry. We investigated relationships between dietary macronutrient composition and long-term changes in weight and waist circumference in participants of the EPIC-Italy study. Methods & Results. 32 119 partic...

Background: High carbohydrate intake raises blood triglycerides, glucose, and insulin; reduces HDLs; and may increase risk of coronary heart disease (CHD). Epidemiological studies indicate that high dietary glycemic index (GI) and glycemic load (GL) are associated with increased CHD risk. Objectives: The aim of this study was to determine whethe...

A substantial proportion of epithelial ovarian cancer (EOC) arises in the fallopian tube and other epithelia of the upper genital tract; these epithelia may incur damage and neoplastic transformation after sexually transmitted infections (STI) and pelvic inflammatory disease. We investigated the hypothesis that past STI infection, particularly Chla...

Background: While Helicobacter pylori (H. pylori) is the major cause of gastric cancer, it has also been suggested to be involved in colorectal cancer (CRC) development. However, prospective studies addressing H. pylori and CRC are sparse and inconclusive. We assessed the association of antibody responses to H. pylori proteins with CRC in the Euro...

Introduction Chronic inflammation plays a critical role in lymphomagenesis and several dietary factors seem to be involved its regulation. The aim of the current study was to assess the association between the inflammatory potential of the diet and the risk of lymphoma and its subtypes in the European Investigation into Cancer and Nutrition (EPIC)...

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 c...

Background: Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle...

Objective: Colorectal cancer (CRC) is one of the most diagnosed malignant cancers worldwide. Rectal cancers (Rcs) represent one-third of all CRCs. Cigarette smoking and alcohol drinking are two underestimated risk factors for RC. We aimed to evaluate the role of alcohol consumption and cigarette smoking in modulating RC risk and to estimate the at...

Background aims: Human studies examining associations between circulating levels of insulin-like growth factor 1 (IGF1) and insulin-like growth factor binding protein 3 (IGFBP3) and colorectal cancer risk have reported inconsistent results. We conducted complementary serologic and Mendelian randomization (MR) analyses to determine whether alterati...

Background Processed meat intake is associated with a higher risk of colorectal and stomach cancers, coronary artery disease, and type 2 diabetes and with higher mortality, but the estimation of intake of different processed meat products in this heterogeneous food group in epidemiological studies remains challenging. Objective This work aimed at...

Importance Soft drinks are frequently consumed, but whether this consumption is associated with mortality risk is unknown and has been understudied in European populations to date. Objective To examine the association between total, sugar-sweetened, and artificially sweetened soft drink consumption and subsequent total and cause-specific mortality...

Background: The relation of dairy product consumption to health and mortality is controversial. Objectives: We investigated associations of consumption of various dairy products with mortality in the Italian cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC)-Italy study. Methods: Dairy product consumption was ass...

Background: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrat...

Background: Population-specificity of exploratory dietary patterns limits their generalizability in investigations with type 2 diabetes incidence. Objective: The aim of this study was to derive country-specific exploratory dietary patterns, investigate their association with type 2 diabetes incidence, and replicate diabetes-associated dietary pa...

Background: It is well established that estrogens and other hormonal factors influence breast cancer susceptibility. We hypothesized that a woman's total lifetime estrogen exposure accumulates changes in DNA methylation, detectable in the blood, which could be used in risk assessment for breast cancer. Methods: An estimated lifetime estrogen exp...

Selenoprotein genetic variations and suboptimal selenium (Se) levels may contribute to the risk of colorectal cancer (CRC) development. We examined the association between CRC risk and genotype for single nucleotide polymorphisms (SNPs) in selenoprotein and Se metabolic pathway genes. Illumina Goldengate assays were designed and resulted in the gen...

Background: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We...

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. Th...

Diet is the primary source of cadmium—a proven Group 1 human carcinogen—for non‐smokers. Observational studies investigating the effect of cadmium from food sources on breast cancer risk have produced inconsistent results. We examined the association between dietary cadmium and risk of breast cancer defined by estrogen receptor (ER), progesterone r...

Dietary pattern analysis is a method of dietary analysis that considers the cumulative and interactive effects among dietary components to reflect the complexity of the human diet. It is a modern, comprehensive, and "holistic" approach that can overcome several methodological limitations in studying the association between human diet and health. Th...

Table S1. Distribution of participants and bladder cancer cases across nine EPIC countries

Background Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer ri...

Purpose: There is inconsistent evidence regarding the relationship between higher intake of nuts, being an energy-dense food, and weight gain. We investigated the relationship between nut intake and changes in weight over 5 years. Methods: This study includes 373,293 men and women, 25-70 years old, recruited between 1992 and 2000 from 10 Europea...

Importance There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening c...

Background: Epidemiologic evidence indicates common risk factors, including air pollution exposure, for respiratory and cardiovascular diseases, suggesting the involvement of common altered molecular pathways. Objectives: The goal was to find intermediate metabolites or metabolic pathways that could be associated with both air pollutants and hea...

Previous in vitro and case‐control studies have found an association between the insulin‐like growth factor (IGF)‐axis and bladder cancer risk. Circulating concentrations of IGF‐I have also been found to be associated with an increased risk of several cancer types; however, the relationship between pre‐diagnostic circulating IGF‐I concentrations an...

Breast cancer is the most common female cancer worldwide and makes up 25% of all cancers diagnosed in women. There is a need for improved risk assessment methods to identify women at high risk before the disease develops. It is well established that estrogens are involved in estrogen receptor positive (ER+) breast cancer carcinogenesis, however the...

Background: Accurate assessment of polyphenol intakes is needed in epidemiologic research in order to study their health effects, and this can be particularly challenging in international study settings. Objective: The purpose of this work is to describe the procedures to prepare a comprehensive polyphenol food-composition database that was used...

Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health. Methods: We pooled...