TY - JOUR
T1 - Development and validation of a lifestyle-based model for colorectal cancer risk prediction
T2 - the LiFeCRC score
AU - Aleksandrova, Krasimira
AU - Reichmann, Robin
AU - Kaaks, Rudolf
AU - Jenab, Mazda
AU - Bueno-de-Mesquita, H Bas
AU - Dahm, Christina C
AU - Eriksen, Anne Kirstine
AU - Tjønneland, Anne
AU - Artaud, Fanny
AU - Boutron-Ruault, Marie-Christine
AU - Severi, Gianluca
AU - Hüsing, Anika
AU - Trichopoulou, Antonia
AU - Karakatsani, Anna
AU - Peppa, Eleni
AU - Panico, Salvatore
AU - Masala, Giovanna
AU - Grioni, Sara
AU - Sacerdote, Carlotta
AU - Tumino, Rosario
AU - Elias, Sjoerd G
AU - May, Anne M
AU - Borch, Kristin B
AU - Sandanger, Torkjel M
AU - Skeie, Guri
AU - Sánchez, Maria-Jose
AU - Huerta, José María
AU - Sala, Núria
AU - Gurrea, Aurelio Barricarte
AU - Quirós, José Ramón
AU - Amiano, Pilar
AU - Berntsson, Jonna
AU - Drake, Isabel
AU - van Guelpen, Bethany
AU - Harlid, Sophia
AU - Key, Tim
AU - Weiderpass, Elisabete
AU - Aglago, Elom K
AU - Cross, Amanda J
AU - Tsilidis, Konstantinos K
AU - Riboli, Elio
AU - Gunter, Marc J
N1 - Funding Information:
The authors express special thanks to Ellen Kohlsdorf (EPIC-Potsdam, Germany) and Bertrand Hemon (IARC-Lyon, France) for their work on data management. We thank the Human Study Centre (HSC) of the German Institute of Human Nutrition Potsdam-Rehbrücke, and the head of the HSC, Manuela Bergmann, for the contribution to the study design and leading the underlying processes of data generation. We are grateful to all the participants who have been part of the project and to the many members of the study teams at different study centers who have enabled this research.
Funding Information:
This work was supported by the German Research Foundation (DFG) (grant AL 1784/3-1), which funded the research position of Dr. Aleksandrova for organizing study conduct and analysis. 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); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) and Federal Ministry of Education and Research (BMBF) (Germany); 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), Statistics Netherlands (The Netherlands); Health Research Fund (FIS), Instituto de salud Carlos III PI13/00061 to Granada; PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236), Navarra and Catalonia (Catalan Institute of Oncology – ICO-IDIBELL) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (C864/A14136 to EPIC-Norfolk and C8221/A19170 to EPIC-Oxford), Medical Research Council (MR/N003284/1 and MC-UU_12015/1 to EPIC-Norfolk and MR/M012190/1 to EPIC-Oxford) (United Kingdom). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Open Access funding enabled and organized by Projekt DEAL.
Publisher Copyright:
© 2020, The Author(s).
PY - 2021/12
Y1 - 2021/12
N2 - 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.
AB - 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.
KW - Cancer prevention
KW - Colorectal cancer
KW - Lifestyle behaviour
KW - Risk prediction
KW - Risk screening
UR - http://www.scopus.com/inward/record.url?scp=85098547972&partnerID=8YFLogxK
U2 - 10.1186/s12916-020-01826-0
DO - 10.1186/s12916-020-01826-0
M3 - Article
C2 - 33390155
SN - 1741-7015
VL - 19
SP - 1
EP - 19
JO - BMC Medicine
JF - BMC Medicine
IS - 1
ER -