Review for 10.1186/s12876-025-03938-4 (2025)

Title: Worldwide burden and cross-regional health inequalities of high BMI-attributable
colorectal cancer by gender from 1990 to 2021, with predictions through 2041
Version: 0 Date: 30 Mar 2025
Reviewer's report:
The study analyzes the global burden of colorectal cancer (CRC) attributable to overweight from
1990 to 2021, with projections through 2036, using data from the Global Burden of Disease
(GBD) Study 2021. The research examines deaths and disability-adjusted life years (DALYs)
across different regions, countries, age groups, and genders. Key findings reveal that in 2021,
approximately 99,268 deaths and 2.36 million DALYs globally were attributable to overweight-
related CRC, representing a 139% and 133% increase respectively since 1990. The authors
identified significant disparities, with high SDI regions experiencing the highest burden but
showing decreasing trends, while middle SDI regions demonstrated concerning increases.
Major Concerns and Limitations
Methodological Constraints
The study’s scope is limited to individuals aged #20 years with BMI #25 kg/m², excluding
younger populations and failing to stratify by different BMI categories (e.g., BMI #30 kg/
m² or BMI #40 kg/m²). This approach misses the opportunity to assess how varying degrees
of obesity might differentially impact CRC outcomes, potentially obscuring important dose-
response relationships between BMI severity and cancer risk.
Absence of Incidence Data
A significant limitation is the exclusion of CRC incidence data, which prevents the assessment
of overweight’s role in cancer initiation versus progression. Without this information, the study
cannot differentiate whether overweight primarily affects CRC development, progression, or
mortality outcomes, limiting the translational value of the findings for preventive interventions.
Data Quality Heterogeneity
The GBD database exhibits inherent limitations including data collection heterogeneity and
potential errors that may introduce bias into the estimates. This is particularly problematic for
low SDI regions, where incomplete surveillance systems likely underestimate the true burden
of CRC attributable to overweight. These data quality issues undermine the reliability of cross-
regional comparisons and trend analyses in resource-limited settings.
Causal Inference Limitations
While establishing associations between overweight and CRC burden, the study cannot
definitively establish causality due to its observational nature. The inability to control for
all potential confounding factors (such as dietary patterns, physical activity, genetics, and
healthcare access) weakens the etiological conclusions that can be drawn from the findings.
Minor Concerns and Limitations
Limited Data Integration
The study relies exclusively on GBD data without integrating information from other
epidemiological databases like SEER or GLOBOCAN. This single-source approach may miss
valuable complementary insights that could validate findings or address gaps in the GBD dataset,
particularly regarding cancer stage and treatment information.
Regional Granularity
While providing country-level data, the study may not capture important within-country
variations, particularly in large, diverse nations. This limitation restricts the applicability of
findings for sub-national health planning and resource allocation, especially in countries with
significant internal healthcare disparities.
Mechanistic Understanding
The paper provides limited exploration of biological mechanisms linking overweight to
CRC, which could inform targeted intervention development. A deeper mechanistic analysis
would enhance the translational value of the epidemiological findings and potentially identify
biomarkers for risk assessment or novel therapeutic targets.
Projection Methodology
The ARIMA model used for projections assumes that historical trends will continue, potentially
overlooking future shifts in obesity prevalence, healthcare advances, or policy interventions.
This deterministic approach to forecasting may not adequately capture the dynamic and complex
interplay of factors that will influence future CRC burden.
Policy Recommendations
While briefly mentioning the need for public health interventions, the manuscript lacks detailed
recommendations for addressing overweight-attributable CRC burden. The authors suggest
general “comprehensive, region-specific, and age-appropriate strategies” but do not provide
actionable guidance for policymakers or healthcare systems.