A probabilistic model for explaining the points achieved by a team in football competition. Forecasting and regression with applications to the Spanish competition

In the last decades, a lot of research papers applying statistical methods for analysing sports data have been published. Football, also called soccer, is one of the most popular sports all over the world organised in national championships in a round robin format in which the team reaching the most points at the end of the tournament wins the competition. The aim of this work is to develop a suitable probability model for studying the points achieved by a team in a football match. For this purpose, we built a discrete probability distribution taking values, zero for losing, one for a draw and three for a victory. We test its performance using data from the Spanish Football League (First division) during the 2013-14 season. Furthermore, the model provides an attractive framework for predicting points and incorporating covariates in order to study the factors affecting the points achieved by the teams.Peer Reviewe

Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN)

The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002–2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002–2007 and 2008–2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, agestandardized five-year net survival was higher in women (61.7%, 95% CI 61.4–62.1%) than in men (55.3%, 95% CI 55.0–55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0–3.7%) in men and 2.5% (95% CI 2.0–3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0–6.0%) and rectal cancers (4.5%, 95% CI 3.2–5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services’ effectiveness

Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Background: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known. Methods: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case–control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; <1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)<25 kg/m2 or waist circumference (WC)<80 cm or waist-to-hip ratio (WHR)<0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/ NW, and (iv) MU/OW. Results: In a multivariable-adjusted conditional logistic regression model, compared withMH/NWindividuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05–2.10 and ORWHR, 1.68; 95% CI, 1.21– 2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73–3.27; ORWC, 2.69; 95% CI, 1.92–3.77 and ORWHR, 1.83; 95% CI, 1.32–2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24–3.04). Conclusions: Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesityrelated pathways are relevant for the development of this cancer beyond insulin. Impact: Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.World Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDanish Cancer SocietyLigue nationale contre le cancerInstitut Gustave RoussyMutuelle Generale de l'Education NationaleInstitut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeHelmholtz AssociationGerman Institute of Human Nutrition PotsdamRehbruecke (DIfE)Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancroCompagnia di San PaoloConsiglio Nazionale delle Ricerche (CNR)Dutch Ministry of Public Health, Welfare and Sports (VWS)Netherlands Cancer Registry (NKR)LK Research FundsDutch Prevention Funds Netherlands Organization for Scientific Research (NWO)World Cancer Research Fund (WCRF-ERC) 232997Netherlands GovernmentHealth Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII)Junta de AndaluciaPrincipality of AsturiasBasque GovernmentRegional Government of MurciaRegional Government of NavarraCatalan Institute of OncologyICO (Spain)Swedish Cancer Society Swedish Research CouncilEuropean CommissionCounty Council of SkaneCounty Council of Vasterbotten (Sweden)Cancer Research UK 14136 C8221/A29017 C19335/A21351UK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission 1000143 MR/M012190/

Prospective evaluation of 92 serum protein biomarkers for early detection of ovarian cancer

The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London-, which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra,-and the Catalan Institute of OncologyICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (MR/N003284/1, MC-UU 12015/1 and MC UU_00006/1to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). Open Access funding enabled and organized by Projekt DEAL.BACKGROUND: CA125 is the best available yet insufficiently sensitive biomarker for early detection of ovarian cancer. There is a need to identify novel biomarkers, which individually or in combination with CA125 can achieve adequate sensitivity and specificity for the detection of earlier-stage ovarian cancer. METHODS: In the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we measured serum levels of 92 preselected proteins for 91 women who had blood sampled ≤18 months prior to ovarian cancer diagnosis, and 182 matched controls. We evaluated the discriminatory performance of the proteins as potential early diagnostic biomarkers of ovarian cancer. RESULTS: Nine of the 92 markers; CA125, HE4, FOLR1, KLK11, WISP1, MDK, CXCL13, MSLN and ADAM8 showed an area under the ROC curve (AUC) of ≥0.70 for discriminating between women diagnosed with ovarian cancer and women who remained cancerfree. All, except ADAM8, had shown at least equal discrimination in previous case-control comparisons. The discrimination of the biomarkers, however, was low for the lag-time of >9–18 months and paired combinations of CA125 with any of the 8 markers did not improve discrimination compared to CA125 alone. CONCLUSION: Using pre-diagnostic serum samples, this study identified markers with good discrimination for the lag-time of 0–9 months. However, the discrimination was low in blood samples collected more than 9 months prior to diagnosis, and none of the markers showed major improvement in discrimination when added to CA125.World Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDanish Cancer SocietyLigue Contre le Cancer (France)Institut Gustave Roussy (France)Mutuelle Generale de l'Education Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeGerman Cancer Research Center (DKFZ) (Germany)German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) (Germany)Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancroCompagnia di San PaoloConsiglio Nazionale delle Ricerche (CNR)Netherlands GovernmentWorld Cancer Research Fund International (WCRF)Netherlands GovernmentHealth Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII) (Spain)Junta de AndaluciaRegional Government of Asturias (Spain)Regional Government of Basque Country (Spain)Regional Government of Murcia (Spain)Regional Government of Navarra (Spain)Catalan Institute of OncologyICO (Spain)Swedish Cancer SocietySwedish Research CouncilCounty Council of Skane (Sweden)County Council of Vasterbotten (Sweden)Cancer Research UK C864/A14136 C8221/A29017UK Research & Innovation (UKRI)Medical Research Council UK (MRC) MR/N003284/1 MC-UU 12015/1 MC UU_00006/1 MR/M012190/1Projekt DEA

A body shape index (ABSI) is associated inversely with post-menopausal progesterone-receptor-negative breast cancer risk in a large European cohort

Background Associations of body shape with breast cancer risk, independent of body size, are unclear because waist and hip circumferences are correlated strongly positively with body mass index (BMI). Methods We evaluated body shape with the allometric “a body shape index” (ABSI) and hip index (HI), which compare waist and hip circumferences, correspondingly, among individuals with the same weight and height. We examined associations of ABSI, HI, and BMI (per one standard deviation increment) with breast cancer overall, and according to menopausal status at baseline, age at diagnosis, and oestrogen and progesterone receptor status (ER+/-PR+/-) in multivariable Cox proportional hazards models using data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Results During a mean follow-up of 14.0 years, 9011 incident breast cancers were diagnosed among 218,276 women. Although there was little evidence for association of ABSI with breast cancer overall (hazard ratio HR = 0.984; 95% confidence interval: 0.961–1.007), we found borderline inverse associations for post-menopausal women (HR = 0.971; 0.942-1.000; n = 5268 cases) and breast cancers diagnosed at age ≥ 55 years (HR = 0.976; 0.951–1.002; n = 7043) and clear inverse associations for ER + PR- subtypes (HR = 0.894; 0.822–0.971; n = 726) and ER-PR- subtypes (HR = 0.906; 0.835–0.983 n = 759). There were no material associations with HI. BMI was associated strongly positively with breast cancer overall (HR = 1.074; 1.049–1.098), for post-menopausal women (HR = 1.117; 1.085–1.150), for cancers diagnosed at age ≥ 55 years (HR = 1.104; 1.076–1.132), and for ER + PR + subtypes (HR = 1.122; 1.080–1.165; n = 3101), but not for PR- subtypes. Conclusions In the EPIC cohort, abdominal obesity evaluated with ABSI was not associated with breast cancer risk overall but was associated inversely with the risk of post-menopausal PR- breast cancer. Our findings require validation in other cohorts and with a larger number of PR- breast cancer cases.World Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonCancer Research UK 14136 C8221/A29017UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/

Dietary intake of trans fatty acids and breast cancer risk in 9 European countries

The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPICNorfolk, MR/M012190/1 to EPIC-Oxford) (UK). We thank the Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, and the National Institute for Public Health and the Environment (RIVM)-Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study.For information on how to submit an application for gaining access to EPIC data and/or biospecimens, please follow the instructions at http://epic.iarc.fr/ access/index.php.Informed consent was given by all study participants, and ethical approval for the entire EPIC cohort was obtained from the Institutional Review Board of the International Agency for Research on Cancer in Lyon, France, under protocol numbers SC/24/4 and SC/24/6, as well as from local ethics committees in the participating countries.The authors thank the EPIC participants and staff for their valuable contribution to this research and Bertrand Hemon (International Agency for Research on Cancer) for managing the data for the EPIC project.Background Trans fatty acids (TFAs) have been hypothesised to influence breast cancer risk. However, relatively few prospective studies have examined this relationship, and well-powered analyses according to hormone receptor-defined molecular subtypes, menopausal status, and body size have rarely been conducted. Methods In the European Prospective Investigation into Cancer and Nutrition (EPIC), we investigated the associations between dietary intakes of TFAs (industrial trans fatty acids [ITFAs] and ruminant trans fatty acids [RTFAs]) and breast cancer risk among 318,607 women. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusted for other breast cancer risk factors. Results After a median follow-up of 8.1 years, 13,241 breast cancer cases occurred. In the multivariable-adjusted model, higher total ITFA intake was associated with elevated breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). A similar positive association was found between intake of elaidic acid, the predominant ITFA, and breast cancer risk (HR for highest vs lowest quintile, 1.14, 95% CI 1.06-1.23; P trend = 0.001). Intake of total RTFAs was also associated with higher breast cancer risk (HR for highest vs lowest quintile, 1.09, 95% CI 1.01-1.17; P trend = 0.015). For individual RTFAs, we found positive associations with breast cancer risk for dietary intakes of two strongly correlated fatty acids (Spearman correlation r = 0.77), conjugated linoleic acid (HR for highest vs lowest quintile, 1.11, 95% CI 1.03-1.20; P trend = 0.001) and palmitelaidic acid (HR for highest vs lowest quintile, 1.08, 95% CI 1.01-1.16; P trend = 0.028). Similar associations were found for total ITFAs and RTFAs with breast cancer risk according to menopausal status, body mass index, and breast cancer subtypes. Conclusions These results support the hypothesis that higher dietary intakes of ITFAs, in particular elaidic acid, are associated with elevated breast cancer risk. Due to the high correlation between conjugated linoleic acid and palmitelaidic acid, we were unable to disentangle the positive associations found for these fatty acids with breast cancer risk. Further mechanistic studies are needed to identify biological pathways that may underlie these associations.European Commission European Commission Joint Research CentreInternational Agency for Research on CancerDanish Cancer SocietyLigue Contre le Cancer (France)Institut Gustave Roussy (France)Mutuelle Generale de l'Education Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeGerman Cancer Research Center (DKFZ) (Germany)Federal Ministry of Education & Research (BMBF)Deutsche KrebshilfeDeutsches Krebsforschungszentrum (Germany)Federal Ministry of Education & Research (BMBF)Hellenic Health Foundation (Greece)Associazione Italiana per la Ricerca sul Cancro (AIRC)Consiglio Nazionale delle Ricerche (CNR)Dutch Ministry of Public Health, Welfare and Sports (VWS)Netherlands Cancer Registry (NKR)LK Research FundsDutch Prevention FundsNetherlands Organization for Scientific Research (NWO)World Cancer Research Fund International (WCRF)Instituto de Salud Carlos III PI13/00061 PI13/01162Junta de AndaluciaCatalan Institute of Oncology (Spain)Swedish Cancer Society Swedish Research CouncilCounty Council of Skane (Sweden)County Council of Vasterbotten (Sweden)Cancer Research UK 14136 C570/A16491 C8221/A19170UK Research & Innovation (UKRI) Medical Research Council UK (MRC) 1000143 MR/M012190/1Julius Center for Health Sciences and Primary Care, University Medical Center UtrechtNational Institute for Public Health and the Environment (RIVM)-Bilthoven, the NetherlandsNordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway)Regional Government of Asturias (Spain)Regional Government of Basque Country (Spain)Regional Government of Murcia (Spain)Regional Government of Navarra (Spain)Junta de AndaluciaERC-2009-AdG 23299

Circulating inflammatory biomarkers, adipokines and breast cancer risk—a case-control study nested within the EPIC cohort

This work was funded by the French National Cancer Institute (grant number 2016-128) and the World Cancer Research Fund (grant number 2017/1614). Manon Cairat was supported by a PhD fellowship from la Ligue Nationale Contre le Cancer. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology -ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skane and Vasterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPICNorfolk; MR/M012190/1 to EPIC-Oxford). (United Kingdom). The funders were not involved in designing the study; collecting, analyzing or interpreting the data; or in writing or submitting the manuscript for publication.Background: Inflammation has been hypothesized to play a role in the development and progression of breast cancer and might differently impact breast cancer risk among pre and postmenopausal women. We performed a nested case-control study to examine whether pre-diagnostic circulating concentrations of adiponectin, leptin, c-reactive protein (CRP), tumour necrosis factor-α, interferon-γ and 6 interleukins were associated with breast cancer risk, overall and by menopausal status. Methods: Pre-diagnostic levels of inflammatory biomarkers were measured in plasma from 1558 case-control pairs from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. We used conditional logistic regression to estimate the odds ratios (ORs) of breast cancer at blood collection, per one standard deviation increase in biomarker concentration. Results: Cases were diagnosed at a mean age of 61.4 years on average 8.6 years after blood collection. No statistically significant association was observed between inflammatory markers and breast cancer risk overall. In premenopausal women, borderline significant inverse associations were observed for leptin, leptin-to-adiponectin ratio and CRP [OR= 0.89 (0.77–1.03), OR= 0.88 (0.76–1.01) and OR= 0.87 (0.75–1.01), respectively] while positive associations were observed among postmenopausal women [OR= 1.16 (1.05–1.29), OR= 1.11 (1.01–1.23), OR= 1.10 (0.99–1.22), respectively]. Adjustment for BMI strengthened the estimates in premenopausal women [leptin: OR = 0.83 (0.68– 1.00), leptin-to-adiponectin ratio: OR = 0.80 (0.66–0.97), CRP: OR = 0.85 (0.72–1.00)] but attenuated the estimates in postmenopausal women [leptin: OR = 1.09 (0.96–1.24), leptin-to-adiponectin ratio: OR = 1.02 (0.89–1.16), CRP: OR = 1.04 (0.92–1.16)]. Conclusions: Associations between CRP, leptin and leptin-to-adiponectin ratio with breast cancer risk may represent the dual effect of obesity by menopausal status although this deserves further investigation.Institut National du Cancer (INCA) France 2016-128World Cancer Research Fund International (WCRF) 2017/1614Ligue nationale contre le cancerWorld Health OrganizationNIHR Imperial Biomedical Research Centre (BRC)Danish Cancer SocietyLigue nationale contre le cancerInstitut Gustave RoussyMutuelle Generale de l'Education NationaleInstitut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeHelmholtz AssociationFederal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancroConsiglio Nazionale delle Ricerche (CNR)Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research FundsDutch Prevention FundsNetherlands Organization for Scientific Research (NWO)World Cancer Research Fund (WCRF), Statistics NetherlandsHealth Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII)Catalan Institute of Oncology -ICO (Spain)Swedish Cancer SocietySwedish Research CouncilEuropean CommissionCounty Councils of SkaneVasterbotten (Sweden)Cancer Research UK 14136 C8221/A29017UK Research & Innovation (UKRI)Medical Research Council UK (MRC)European Commission 1000143 MR/M012190/

Prospective analysis of circulating metabolites and endometrial cancer risk

This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the This work was supported by Cancer Research UK (CRUK) (grant number C19335/A21351, to MJG and HK) . The metabolomics infrastructure in the Division of Cancer, Imperial College London is supported by the Imperial College Experimental Can-cer Medicine Centre, the Imperial College Cancer Research UK Centre and the NIHR Imperial Biomedical Research Centre (APS & HK) . The co-ordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Im-perial Biomedical Research Centre (BRC) . The national cohorts are sup-ported by: Danish Cancer Society (Denmark) ; Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Generale de l'Education Nationale, Institut National de la Sante et de la Recherche Medicale (INSERM) (France) ; German Cancer Aid, German Cancer Research Center (DKFZ) , German Institute of Human Nutrition PotsdamRehbruecke (DIfE) , Federal Ministry of Education and Research (BMBF) (Germany) ; Associazione Italiana per la Ricerca sul CancroAIRCItaly, Compagnia di SanPaolo and National Research Council (Italy) ; Dutch Ministry of Public Health, Welfare and Sports (VWS) , Netherlands Can-cer Registry (NKR) , LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland) , World Cancer Research Fund (WCRF) , Statistics Netherlands (The Netherlands) ; Health Research Fund (FIS) -Instituto de Salud Carlos III (ISCIII) , Regional Governments of Andalucia, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain) ; Swedish Cancer Society, Swedish Research Council and County Councils of Skkne and Vasterbotten (Sweden) ; Cancer Research UK (14136 to EPICNorfolk; C8221/A29017 to EPICOxford) , Medical Research Council (1000143 to EPICNorfolk; MR/M012190/1 to EPICOxford) . (United Kingdom) .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 from853 case-control pairs fromthe European Prospective Investigation into Cancer and Nutrition (EPIC). Methods. A total of 129metabolites (acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexoses, and sphingolipids) were measured by liquid chromatography-mass spectrometry. Conditional logistic regression estimated the associations of metabolites with endometrial cancer risk. An analysis focusing on clusters of metabolites using the bootstrap lasso method was also employed. Results. After adjustment for body mass index, sphingomyelin [SM] C18:0was positively (OR1SD: 1.18,95%CI: 1.05–1.33), and glycine, serine, and free carnitine (C0) were inversely (OR1SD: 0.89, 95% CI: 0.80–0.99; OR1SD: 0.89, 95% CI: 0.79–1.00 and OR1SD: 0.91, 95% CI: 0.81–1.00, respectively) associated with endometrial cancer risk. Serine, C0 and two sphingomyelins were selected by the lasso method in >90% of the bootstrap samples. The ratio of esterified to free carnitine (OR1SD: 1.14, 95% CI: 1.02–1.28) and that of short chain to free acylcarnitines (OR1SD: 1.12, 95% CI: 1.00–1.25) were positively associated with endometrial cancer risk. Further adjustment for C-peptide or other endometrial cancer risk factors only minimally altered the results. Conclusion. These findings suggest that variation in levels of glycine, serine, SMC18:0 and free carnitine may represent specific pathways linked to endometrial cancer development. If causal, these pathways may offer novel targets for endometrial cancer prevention.Cancer Research UK C19335/A21351Imperial College Experimental Cancer Medicine Centre Imperial College Cancer Research UK CentreNIHR Imperial Biomedical Research CentreWorld Health OrganizationDepartment of Epidemiology and Biostatistics, School of Public Health, Imperial College LondonDanish Cancer SocietyLigue Contre le Cancer (France) Institut Gustave Roussy (France) Mutuelle Generale de l'Education Nationale (France)Institut National de la Sante et de la Recherche Medicale (Inserm)Deutsche KrebshilfeGerman Cancer Research Center (DKFZ) (Germany) German Institute of Human Nutrition PotsdamRehbruecke (DIfE) (Germany)Federal Ministry of Education & Research (BMBF)Fondazione AIRC per la ricerca sul cancro Compagnia di San Paolo Consiglio Nazionale delle Ricerche (CNR)Netherlands Government Netherlands GovernmentWorld Cancer Research Fund International (WCRF)Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII) (Spain)Junta de AndaluciaRegional Government of Asturias (Spain)Regional Government of Basque Country (Spain)Regional Government of Murcia (Spain)Regional Government of Navarra (Spain)Catalan Institute of Oncology-ICO (Spain)Swedish Cancer SocietySwedish Research CouncilCounty Council of Skkne (Sweden)County Council of Vasterbotten (Sweden)Cancer Research UK 14136 C8221/A29017UK Research & Innovation (UKRI)Medical Research Council UK (MRC) 1000143 MR/M012190/