Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer

Alexi N. Archambault, Yi Lin, Jihyoun Jeon, Tabitha A. Harrison, D. Timothy Bishop, Hermann Brenner, Graham Casey, Andrew T. Chan, Jenny Chang-Claude, Jane C. Figueiredo, Steven Gallinger, Stephen B. Gruber, Marc J. Gunter, Michael Hoffmeister, Mark A. Jenkins, Temitope O. Keku, Loïc Le Marchand, Li Li, Victor Moreno, Polly A. NewcombRish Pai, Patrick S. Parfrey, Gad Rennert, Lori C. Sakoda, Robert S. Sandler, Martha L. Slattery, Mingyang Song, Aung Ko Win, Michael O. Woods, Neil Murphy, Peter T. Campbell, Yu Ru Su, Anne Zeleniuch-Jacquotte, Peter S. Liang, Mengmeng Du, Li Hsu, Ulrike Peters, Richard B. Hayes

Research output: Contribution to journalArticlepeer-review


Background: Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods: Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results: Early-onset CRC was associated with not regularly using nonsteroidal anti-inflammatory drugs (OR = 1.43, 95% CI = 1.21 to 1.68), greater red meat intake (OR = 1.10, 95% CI = 1.04 to 1.16), lower educational attainment (OR = 1.10, 95% CI = 1.04 to 1.16), alcohol abstinence (OR = 1.23, 95% CI = 1.08 to 1.39), and heavier alcohol use (OR = 1.25, 95% CI = 1.04 to 1.50). No factors exhibited a greater excess in early-onset compared with late-onset CRC. Evaluating risks by anatomic subsite, we found that lower total fiber intake was linked more strongly to rectal (OR = 1.30, 95% CI = 1.14 to 1.48) than colon cancer (OR = 1.14, 95% CI = 1.02 to 1.27; P =. 04). Conclusion: In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.

Original languageEnglish (US)
Article numberpkab029
JournalJNCI Cancer Spectrum
Issue number3
StatePublished - Jun 1 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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