Colorectal Cancer Incidence and Mortality: Current Status, Temporal Trends, and Attributable Risk Factors in 60 Countries (2000–2019)

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Colorectal Cancer Incidence and Mortality: Current Status, Temporal Trends, and Attributable Risk Factors in 60 Countries (2000–2019)

Global Burden of Colorectal Cancer in 2020

Colorectal cancer (CRC) remains a significant global health challenge, ranking as the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths worldwide in 2020. According to GLOBOCAN data, approximately 1.9 million new CRC cases and 935,000 deaths were recorded globally that year. The age-standardized incidence rate (ASIR) and mortality rate (ASMR) were 19.5 and 9.0 per 100,000 population, respectively.

Geographic disparities in CRC burden were stark. European countries exhibited the highest incidence and mortality rates. Hungary had the highest ASIR (45.3 per 100,000), followed by Slovakia (43.9 per 100,000) and Norway (41.9 per 100,000). Conversely, African nations like Guinea (ASIR: 3.3 per 100,000) and Botswana (ASMR: 2.6 per 100,000) reported the lowest rates. In Asia, Japan (ASIR: 38.5 per 100,000) and Singapore (ASMR: 16.2 per 100,000) had elevated rates, while Bangladesh recorded the lowest (ASIR: 3.8; ASMR: 2.3 per 100,000). China accounted for 29% of global CRC cases (555,477 new cases) and 30.6% of deaths (286,162 deaths), reflecting its substantial burden.

A strong correlation was observed between the Human Development Index (HDI) and CRC burden. Countries with very high HDI had ASIRs nearly five times higher than those with low HDI (Figure 1). For instance, Slovakia, a very high-HDI country, reported the highest ASMR (21.0 per 100,000), while Bangladesh, a medium-HDI country, had the lowest.

Temporal Trends in CRC Incidence and Mortality (2000–2019)

Using Joinpoint regression analysis, this study evaluated trends in ASIR and ASMR across 60 countries. Between 2000 and 2019, 33 countries experienced significant increases in CRC incidence (average annual percent change [AAPC]: 0.24–3.82), while 18 countries saw rising mortality (AAPC: 0.41–2.22). These trends were most pronounced in Eastern Europe, Latin America, and Asia (Figure 2).

Group-Specific Trends

Countries were categorized into six groups based on incidence and mortality trends:

  • Group A (Increasing Incidence and Mortality): Included China (AAPC for incidence: 3.82; mortality: 1.18), Ecuador (3.02; 2.22), and Costa Rica (2.64; 1.82).
  • Group C (Increasing Incidence, Decreasing Mortality): Featured countries like South Korea (1.39; -0.54) and Finland (0.48; -0.56), where screening programs likely contributed to mortality reductions.
  • Group F (Decreasing Incidence and Mortality): Comprised 15 high-HDI countries, including Austria (AAPC: -2.19; -2.74) and the United States (-0.69; -1.05), reflecting successful prevention and early detection strategies.

Sex-Specific Trends

Gender disparities were evident. Males exhibited higher incidence increases, with China (AAPC: 4.54), Costa Rica (3.40), and Ecuador (3.11) showing the steepest rises. Females in Ecuador (2.82), China (2.68), and Grenada (2.66) also faced significant increases. Mortality trends mirrored these patterns, with Costa Rica (AAPC: 2.50 in males) and Ecuador (1.97 in females) experiencing the largest surges. Conversely, Austria (-2.89 in males) and Germany (-2.83 in females) led declines in mortality.

Age-Specific Trends

Notably, early-onset CRC (diagnosed in individuals <50 years) rose in 30 countries (AAPC: 0.28–3.62). China (3.62), Costa Rica (3.33), and Mexico (2.78) had the highest increases. Conversely, 13 high-HDI countries, including Austria (-2.09) and Germany (-1.58), reported declines in incidence among those ≥50 years. Strikingly, the U.S. saw a decline in older adults (-0.88) but an increase in younger populations (0.56), highlighting shifting risk profiles.

Risk Factors Associated with CRC Burden

Ecological analyses identified country-level factors linked to CRC incidence and mortality:

  • Lifestyle and Metabolic Factors: Higher alcohol consumption (β = 0.412 for incidence; 0.315 for mortality) and elevated cholesterol levels (β = 0.785 for incidence) were positively associated with CRC burden.
  • Socioeconomic Factors: Unemployment (β = 0.455 for male incidence) and poorer healthcare systems correlated with higher rates. Conversely, higher education levels (β = -0.096 for female mortality) were protective.
  • Regional Variations: In males, alcohol, cholesterol, unemployment, and healthcare quality were significant drivers. For females, universal health coverage (UHC) paradoxically correlated with higher incidence (β = 0.160), possibly due to increased diagnostic access.

Discussion

Declining Trends in High-HDI Countries

Reductions in CRC incidence and mortality in high-HDI countries, such as Austria and the U.S., underscore the impact of screening programs and lifestyle modifications. Colonoscopy and fecal immunochemical testing (FIT) have proven effective, with studies showing up to 49% reductions in incidence and 47% in mortality with screening. The U.S. screening uptake rose from 38% in 2000 to 66% in 2018, aligning with its declining trends.

Rising Burden in Developing Nations

Developing countries, particularly in Asia and Latin America, face escalating CRC rates due to urbanization, dietary shifts (increased processed meat and alcohol consumption), and sedentary lifestyles. China’s rapid increase (AAPC: 3.82) reflects these transitions, compounded by limited screening infrastructure.

Early-Onset CRC: An Emerging Challenge

The rise in early-onset CRC, notably in the U.S., Australia, and Europe, signals urgent public health concerns. While genetic factors (e.g., Lynch syndrome) play a role, modifiable risks like obesity, alcohol, and antibiotic overuse may contribute. Current screening guidelines (typically starting at age 50) may need reevaluation to address this trend.

Limitations and Future Directions

Study limitations include reliance on modeled GBD data and the ecological fallacy risk in associating population-level factors with individual risk. Future research should disaggregate colon and rectal cancer data and explore molecular drivers of early-onset CRC.

Conclusion

This study highlights the dual reality of CRC burden: significant declines in high-HDI countries due to prevention efforts and alarming increases in developing regions. Tailored strategies—such as expanding screening access, promoting healthier lifestyles, and addressing socioeconomic disparities—are critical to mitigating CRC’s global impact.

DOI: doi.org/10.1097/CM9.0000000000001619

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