Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score
Krasimira Aleksandrova,
Robin Reichmann,
Rudolf Kaaks,
Mazda Jenab,
H. Bas Bueno-de-Mesquita,
Christina C. Dahm,
Anne Kirstine Eriksen,
Anne Tjønneland,
Fanny Artaud,
Marie-Christine Boutron-Ruault,
Gianluca Severi,
Anika Hüsing,
Antonia Trichopoulou,
Anna Karakatsani,
Eleni Peppa,
Salvatore Panico,
Giovanna Masala,
Sara Grioni,
Carlotta Sacerdote,
Rosario Tumino,
Sjoerd G. Elias,
Anne M. May,
Kristin B. Borch,
Torkjel M. Sandanger,
Guri Skeie,
Maria-Jose Sánchez,
José María Huerta,
Núria Sala,
Aurelio Barricarte Gurrea,
José Ramón Quirós,
Pilar Amiano,
Jonna Berntsson,
Isabel Drake,
Bethany van Guelpen,
Sophia Harlid,
Tim Key,
Elisabete Weiderpass,
Elom K. Aglago,
Amanda J. Cross,
Konstantinos K. Tsilidis,
Elio Riboli,
Marc J. Gunter
Affiliations
Krasimira Aleksandrova
Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Robin Reichmann
Nutrition, Immunity and Metabolism Senior Scientist Group, Department of Nutrition and Gerontology, German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Rudolf Kaaks
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
Mazda Jenab
International Agency for Research on Cancer, World Health Organization
H. Bas Bueno-de-Mesquita
National Institute for Public Health and the Environment (RIVM)
Christina C. Dahm
Department of Public Health, Aarhus University
Anne Kirstine Eriksen
Danish Cancer Society Research Center
Anne Tjønneland
Danish Cancer Society Research Center
Fanny Artaud
CESP, Faculté de Medicine, Université Paris-Saclay
Marie-Christine Boutron-Ruault
CESP, Faculté de Medicine, Université Paris-Saclay
Gianluca Severi
CESP, Faculté de Medicine, Université Paris-Saclay
Anika Hüsing
Division of Cancer Epidemiology, German Cancer Research Center (DKFZ)
Antonia Trichopoulou
Hellenic Health Foundation
Anna Karakatsani
Hellenic Health Foundation
Eleni Peppa
Hellenic Health Foundation
Salvatore Panico
EPIC Centre of Naples, Dipartimento di Medicina Clinica e Chirurgia, University of Naples Federico II
Giovanna Masala
Cancer Risk Factors and Lifestyle Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network – ISPRO
Sara Grioni
Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
Carlotta Sacerdote
Unit of Cancer Epidemiology, Città della Salute e della Scienza University-Hospital and Center for Cancer Prevention (CPO)
Rosario Tumino
Cancer Registry and Histopathology Department, Provincial Health Authority (ASP)
Sjoerd G. Elias
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University
Anne M. May
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht University
Kristin B. Borch
Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway
Torkjel M. Sandanger
Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway
Guri Skeie
Department of Community Medicine, Health Faculty, UiT-the Arctic university of Norway
Maria-Jose Sánchez
Escuela Andaluza de Salud Pública (EASP)
José María Huerta
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)
Núria Sala
Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Translational Research Laboratory, Catalan Institute of Oncology (ICO)
Aurelio Barricarte Gurrea
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)
José Ramón Quirós
Public Health Directorate
Pilar Amiano
Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP)
Jonna Berntsson
Department of Clinical Sciences, Division of Oncology and Pathology, Lund University
Isabel Drake
Department of Clinical Sciences in Malmö, Lund University
Bethany van Guelpen
Department of Radiation Sciences, Oncology, Umeå University
Sophia Harlid
Department of Radiation Sciences, Oncology, Umeå University
Tim Key
Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford
Elisabete Weiderpass
International Agency for Research on Cancer, World Health Organization
Elom K. Aglago
International Agency for Research on Cancer, World Health Organization
Amanda J. Cross
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
Konstantinos K. Tsilidis
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
Elio Riboli
Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
Marc J. Gunter
International Agency for Research on Cancer, World Health Organization
Abstract Background Nutrition and lifestyle have been long established as risk factors for colorectal cancer (CRC). Modifiable lifestyle behaviours bear potential to minimize long-term CRC risk; however, translation of lifestyle information into individualized CRC risk assessment has not been implemented. Lifestyle-based risk models may aid the identification of high-risk individuals, guide referral to screening and motivate behaviour change. We therefore developed and validated a lifestyle-based CRC risk prediction algorithm in an asymptomatic European population. Methods The model was based on data from 255,482 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study aged 19 to 70 years who were free of cancer at study baseline (1992–2000) and were followed up to 31 September 2010. The model was validated in a sample comprising 74,403 participants selected among five EPIC centres. Over a median follow-up time of 15 years, there were 3645 and 981 colorectal cancer cases in the derivation and validation samples, respectively. Variable selection algorithms in Cox proportional hazard regression and random survival forest (RSF) were used to identify the best predictors among plausible predictor variables. Measures of discrimination and calibration were calculated in derivation and validation samples. To facilitate model communication, a nomogram and a web-based application were developed. Results The final selection model included age, waist circumference, height, smoking, alcohol consumption, physical activity, vegetables, dairy products, processed meat, and sugar and confectionary. The risk score demonstrated good discrimination overall and in sex-specific models. Harrell’s C-index was 0.710 in the derivation cohort and 0.714 in the validation cohort. The model was well calibrated and showed strong agreement between predicted and observed risk. Random survival forest analysis suggested high model robustness. Beyond age, lifestyle data led to improved model performance overall (continuous net reclassification improvement = 0.307 (95% CI 0.264–0.352)), and especially for young individuals below 45 years (continuous net reclassification improvement = 0.364 (95% CI 0.084–0.575)). Conclusions LiFeCRC score based on age and lifestyle data accurately identifies individuals at risk for incident colorectal cancer in European populations and could contribute to improved prevention through motivating lifestyle change at an individual level.