Development and validation of a lifestyle-based model for colorectal cancer risk prediction: the LiFeCRC score

Author:

Aleksandrova Krasimira,Reichmann Robin,Kaaks Rudolf,Jenab Mazda,Bueno-de-Mesquita H. Bas,Dahm Christina C.,Eriksen Anne Kirstine,Tjønneland Anne,Artaud Fanny,Boutron-Ruault Marie-Christine,Severi Gianluca,Hüsing Anika,Trichopoulou Antonia,Karakatsani Anna,Peppa Eleni,Panico Salvatore,Masala Giovanna,Grioni Sara,Sacerdote Carlotta,Tumino Rosario,Elias Sjoerd G.,May Anne M.,Borch Kristin B.,Sandanger Torkjel M.,Skeie Guri,Sánchez Maria-Jose,Huerta José María,Sala Núria,Gurrea Aurelio Barricarte,Quirós José Ramón,Amiano Pilar,Berntsson Jonna,Drake Isabel,van Guelpen Bethany,Harlid Sophia,Key Tim,Weiderpass Elisabete,Aglago Elom K.,Cross Amanda J.,Tsilidis Konstantinos K.,Riboli Elio,Gunter Marc J.

Abstract

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.

Funder

German Research Foundation

European Comission

International Agency for Research on Cancer

Danish Cancer Society

Ligue Contre le Cancer

Institut Gustave Roussy

Mutuelle Générale de l’Education Nationale

Institut National de la Santé et de la Recherche Médicale

Deutsche Krebshilfe

Deutsches Krebsforschungszentrum

Bundesministerium für Bildung und Forschung

Associazione Italiana per la Ricerca sul Cancro

National Research Council

Dutch Ministry of Public Health, Welfare and Sports

Netherlands Cancer Registry

LK Research Funds

Dutch Prevention Funds

Dutch ZON

World Cancer Research Fund

Statistics Netherlands

Health Research Fund

Instituto de Salud Carlos III

Regional Governments of Andalucía

Catalan Institute of Oncology – ICO-IDIBELL

Swedish Cancer Society

Swedish Research Council

County Councils of Skåne and Västerbotten

Cancer Research UK

Medical Research Council

Publisher

Springer Science and Business Media LLC

Subject

General Medicine

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