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Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies

Abstract

Globally, colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the second leading cause of cancer death. Arising through three major pathways, including adenoma–carcinoma sequence, serrated pathway and inflammatory pathway, CRC represents an aetiologically heterogeneous disease according to subtyping by tumour anatomical location or global molecular alterations. Genetic factors such as germline MLH1 and APC mutations have an aetiologic role, predisposing individuals to CRC. Yet, the majority of CRC is sporadic and largely attributable to the constellation of modifiable environmental risk factors characterizing westernization (for example, obesity, physical inactivity, poor diets, alcohol drinking and smoking). As such, the burden of CRC is shifting towards low-income and middle-income countries as they become westernized. Furthermore, the rising incidence of CRC at younger ages (before age 50 years) is an emerging trend. This Review provides a comprehensive summary of CRC epidemiology, with emphasis on modifiable lifestyle and nutritional factors, chemoprevention and screening. Overall, the optimal reduction of CRC incidence and mortality will require concerted efforts to reduce modifiable risk factors, to leverage chemoprevention research and to promote population-wide and targeted screening.

Key points

  • Certain global genetic and epigenetic aberrations are disproportionally distributed across the colorectum, which corresponds to aetiological heterogeneity of colorectal cancer (CRC), especially hypermutated cancers, by anatomical location

  • With increasing incidence of CRC at younger ages, there is an urgent need to better identify high-risk individuals younger than 50 years, the age when screening typically starts

  • The constellation of factors associated with westernization, such as obesity, physical inactivity, poor diets, alcohol drinking and smoking, is likely to drive increasing CRC incidence in economically transitioning countries

  • Evidence indicates that aspirin probably confers chemopreventive benefit against CRC, though recommendation for its widespread prophylactic use is currently premature

  • Screening colonoscopy and faecal occult blood test, when implemented appropriately per national financial and medical resources and CRC incidence, could contribute to secondary prevention of CRC

  • The optimal reduction of CRC incidence and mortality will require concerted efforts to reduce modifiable risk factors, to leverage chemoprevention research and to promote population-wide and targeted screening

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Fig. 1: Proportion of colorectal cancer cases associated with sporadic and hereditary factors.
Fig. 2: Descriptive epidemiology of colorectal cancer.
Fig. 3: Time trends of colorectal cancer incidence rates.
Fig. 4: Incidence and mortality of colorectal cancer by age and sex worldwide.
Fig. 5: Pathways of colorectal carcinogenesis.
Fig. 6: Anatomical subtypes of colorectal cancer and their associations with tumour molecular features and other factors.
Fig. 7: Time trends of early-onset and late-onset colorectal cancer incidence rates.
Fig. 8: Introduction of colorectal cancer screening programmes and time trend of colorectal cancer incidence rates and mortality rates.

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Acknowledgements

N.K. was supported by grants from the National Research Foundation of Korea (NRF-2018R1C1B6008822; NRF-2018R1A4A1022589).

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Keum, N., Giovannucci, E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol 16, 713–732 (2019). https://doi.org/10.1038/s41575-019-0189-8

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