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

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.
German Research Foundation (DFG) AL 1784/3-1
European Commission European Commission Joint Research Centre
International Agency for Research on Cancer
Danish Cancer Society
Ligue 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 Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ) (Germany)
Federal Ministry of Education & Research (BMBF)
Hellenic Health Foundation (Greece)
Associazione Italiana per la Ricerca sul Cancro (AIRC)
Consiglio Nazionale delle Ricerche (CNR)
Netherlands Government
World Cancer Research Fund International (WCRF)
Instituto de Salud Carlos III PI13/00061 PI13/01162
Junta de Andalucia
Regional Government of Asturias (Spain)
Regional Government of Basque Country (Spain)
Regional Government of Murcia (Spain) 6236
Regional Government of Navarra (Spain)
Regional Government of Catalonia (Catalan Institute of Oncology -ICO-IDIBELL) (Spain)
Swedish Cancer Society
Swedish Research Council
County Council of Skane (Sweden)
County Council of Vasterbotten (Sweden)
Cancer Research UK C864/A14136 C8221/A19170
UK Research & Innovation (UKRI) Medical Research Council UK (MRC) MR/N003284/1 MC-UU_12015/1 MR/M012190/1
Projekt DEAL