The Burden of Early-Onset Colorectal Cancer and Its Risk Factors from 1990 to 2019: A Systematic Analysis for the Global Burden of Disease Study 2019

Abstract

Background: The incidence of early-onset colorectal cancer (CRC) diagnosed before age 50 has been increasing over the past decades. Hence, we examined the global, regional, and national burden of early-onset CRC and its risk factors from 1990 to 2019. Methods: Using data from the Global Burden of Disease (GBD) Study 2019, we reported the incidence, deaths, and disability-adjusted life-years (DALYs) attributable to the risk factors of early-onset CRC. All estimates were reported with 95% uncertainty intervals (UIs). Results: The global numbers of early-onset CRC for incidence, deaths, and DALYs in 2019 were 225,736 (95% UI, 207,658 to 246,756), 86,545 (80,162 to 93,431), and 4,259,922 (3,942,849 to 4,590,979), respectively. Despite large variations at the regional and national levels, the global incidence rate, death rate, and DALY rate increased from 1990 to 2019. Diets low in milk, diets low in calcium, and alcohol use were the leading risk factors in 2019. From 1990 to 2019, a high body mass index and high fasting plasma glucose ranked remarkably higher among males and females, while smoking and diets low in fiber ranked lower among both sexes, with a more profound change among females. Conclusions: Despite large variations in regional and national levels, the global incidence rate, death rate, and DALY rate increased during the past three decades. These findings may provide policymakers with an accurate quantification of the burden of early-onset CRC and targeted identification of those most at risk to mitigate the burden of early-onset CRC.

Molecular Characteristics of Early-Onset Colorectal Cancer According to Detailed Anatomical Locations: Comparison With Later-Onset Cases

“…In addition, there exists heterogeneity in clinical and pathological features between early-onset and later-onset cases (1,3,(42)(43)(44)(45)(46). Earlyonset MSI-high tumors tend to be related to Lynch syndrome with germline mismatch repair gene mutations, while later-onset MSIhigh tumors tend to be related to CIMP-high tumors with MLH1 promoter hypermethylation (1,59).…”

“…The intestinal microbiota, which likely gradually changes across the entire colorectal length as luminal contents move toward the rectum, has been hypothetically linked with the continuous changes in the prevalence of tumor molecular features along the colorectal segments (13,14). Early-onset colorectal cancer has been associated with certain risk factor profiles, rectal location, signet ring cell histology, and specific tumor characteristics such as high-level MSI, LINE-1 hypomethylation, low/negative CIMP, BRAF wild-type, and lower tumor-infiltrating lymphocytes (1,(3)(4)(5)(6)(7)(42)(43)(44)(45)(46). This study attests to biogeographical (colorectal subsite) heterogeneity in molecular pathological features between early-onset and lateronset cases and even among early-onset cases.…”

Mortality‐to‐incidence ratio of early‐onset colorectal cancer in high‐income Asian and Middle Eastern countries: A systemic analysis of the Global Burden of Diseases Study 2019

“…The Asian countries included were China, Japan, the Republic of Korea, Singapore, Taiwan, and Brunei Darussalam, while the Middle Eastern countries included were Saudi Arabia, Kuwait, the United Arab Emirates, Qatar, Bahrain, Oman, and Israel. The reasons of focusing on high‐income Asian and Middle Eastern countries were the rapid surge in EO‐CRC compared to low‐ and middle‐income Asian and Middle Eastern countries 5–9 . To provide context for the findings, data from Western Europe and the United States were used as reference points for comparison.…”

“…However, the underlying reasons for this upward trend remain largely unclear 2–4 necessitating further research to identify the drivers. Recent studies have highlighted a surge in early‐onset CRC in high‐income Asian countries, including Japan, South Korea, and Taiwan 5–8 . In fact, East Asia exhibits the highest incidence of EO‐CRC, with the region experiencing the most rapid increase in incidence rates from 1990 to 2019 8 .…”

Genetic risk, incident colorectal cancer, and the benefits of adhering to a healthy lifestyle: A prospective study using data from UK Biobank and FinnGen

“…The lifestyle scores were established based on the ACS guidelines for CRC prevention, including exercise, alcohol consumption, body mass index (BMI), and diet (intake of fruits, vegetables, fish, whole grains, processed meat, red meat, and refined grains) ( 11 ). In addition, we included sleep (sleep duration, chronotype, insomnia, snoring, and daytime dozing) and smoking in the lifestyle scores because of the growing interest in the association of sleep disorders and smoking with higher CRC risk ( 14 , 15 , 22 , 23 ). Information on lifestyle factors was obtained at baseline by using a validated touchscreen questionnaire.…”