Systematic Reviews and Meta-analyses
Risk Factors for Early-Onset Colorectal Cancer: A Systematic Review and Meta-analysis

https://doi.org/10.1016/j.cgh.2021.01.037Get rights and content

Background & Aims

Despite the widespread increase in the incidence of early-onset colorectal cancer (EoCRC), the reasons for this increase remain unclear. The objective of this study was to determine risk factors for the development of EoCRC.

Methods

We conducted a systematic literature review and meta-analysis of studies examining non-genetic risk factors for EoCRC, including demographic factors, comorbidities, and lifestyle factors. Random effects meta-analyses were conducted for risk factors that were examined in at least three studies. Heterogeneity was investigated using the Q-test and I2 statistic.

Results

From 3304 initial citations, 20 studies were included in this review. Significant risk factors for EoCRC included CRC history in a first-degree relative (RR 4.21, 95% CI 2.61-6.79), hyperlipidemia (RR 1.62, 95% CI 1.22-2.13), obesity (RR 1.54, 95% CI 1.01-2.35), and alcohol consumption (high vs. non-drinkers) (RR 1.71, 95% CI 1.62-1.80). While smoking was suggestive as a risk factor, the association was not statistically significant (RR 1.35, 95% CI 0.81-2.25). With the exception of alcohol consumption, there was considerable heterogeneity among studies (I2 > 60%). Other potential risk factors included hypertension, metabolic syndrome, ulcerative colitis, chronic kidney disease, dietary factors, sedentary behaviour, and occupational exposure to organic dusts, but these were only examined in one or two studies.

Conclusions

The results of this study advance the understanding of the etiology of EoCRC. High-quality studies conducted on generalizable populations and that comprehensively examine risk factors for EoCRC are required to inform primary and secondary prevention strategies.

Section snippets

Literature Search, Eligibility Criteria, and Screening

The protocol for this systematic review and meta-analysis was registered with PROSPERO (CRD42020185557) and was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses13 and Meta-analysis of Observational Studies in Epidemiology recommendations.14 We systematically searched MEDLINE and Embase databases from inception to August 5, 2020 with a search strategy that was developed by D.E.O and R.L.S. in collaboration with a research librarian at

Study Inclusion and Characteristics of Included Studies

In total, 3304 unique articles were identified during the initial literature search, of which 177 articles plus 7 additional studies from reference lists underwent full-text review. After full-text review, a total of 20 studies examining at least one risk factor for EoCRC were retained, and 14 of these studies were included in the meta-analysis. The most common reasons for exclusion during the full-text review were lack of relevance (n = 82), incorrect study population (n = 31), or

Discussion

In this systematic review and meta-analysis, male sex, Caucasian ethnicity, CRC history in a first-degree relative, hyperlipidemia, obesity, and alcohol consumption were all significantly associated with a higher risk of developing EoCRC. Smoking was a suggestive but statistically non-significant risk factor. With the exception of alcohol consumption, there was considerable heterogeneity among included studies. Other potential risk factors that were less studied included ulcerative colitis,

CRediT Authorship Contributions

Dylan E. O’Sullivan, PhD (Conceptualization: Lead; Data curation: Lead; Formal analysis: Lead; Methodology: Lead; Visualization: Lead; Writing – original draft: Lead)

Robert Liam Sutherland (Conceptualization: Equal; Data curation: Lead; Formal analysis: Supporting; Methodology: Supporting; Writing – review & editing: Equal)

Susanna Town (Conceptualization: Supporting; Data curation: Lead; Formal analysis: Supporting; Methodology: Supporting; Writing – review & editing: Equal)

Kristian Chow

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    Conflicts of interest The authors disclose no conflicts.

    Funding Dylan O’Sullivan is supported by a Canadian Institutes of Health Research (CIHR) Postdoctoral Fellowship.

    This article has an accompanying continuing medical education activity, also eligible for MOC credit on page e1500. Upon completion of this activity, successful learners will be able to, 1) Identify potential risk factors for early-onset colorectal cancer; and, 2) Explain the importance of establishing risk factors for this unique patient population.

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