New research highlights that high blood glucose levels elevate the risk of colorectal cancer, particularly in younger adults, urging the need for tighter glucose control to combat rising cancer rates.
Study: Associations between blood glucose and early- and late-onset colorectal cancer: evidence from two prospective cohorts and Mendelian randomization analyses. Image Credit: Tatiana Shepeleva / Shutterstock
In a recent study published in the Journal of the National Cancer Center, researchers in China investigated the potential associations between blood glucose levels and the risk of colorectal cancer (CRC) of early-onset (EOCRC) and late-onset (LOCRC) types.
They found that elevated blood glucose levels were associated with an increased risk of CRC, with a 61% higher risk for EOCRC in the UK Biobank cohort, compared to a 14% increase for LOCRC. The association in the Kailuan cohort was 65% higher for EOCRC but was not statistically significant due to the smaller sample size. No evidence of non-linear associations was observed.
Background
Previous studies have explored blood glucose levels and CRC risk, but findings remain inconsistent due to small sample sizes and study design limitations. These limitations hinder understanding of the potentially non-linear effects of blood glucose on CRC risk, particularly EOCRC.
CRC remains a leading global health concern, with over 1.9 million new cases and nearly 935,000 deaths in 2020. While overall CRC incidence has decreased due to improved screening methods, EOCRC—diagnosed in individuals under 50—has been rising. EOCRC differs in its epidemiological, clinical, and molecular characteristics compared to LOCRC. Identifying risk factors specific to EOCRC is crucial in addressing this trend.
Mendelian randomization (MR), a method using genetic variants to infer causality, offers a more robust approach to minimize reverse causation and confounding. Non-linear MR is a newer method that helps detect non-linear associations, providing deeper insights into the relationship between blood glucose and CRC risk.
In the present prospective study, researchers analyzed data from two large cohorts to examine the potential linear and non-linear associations between blood glucose levels and the risk of EOCRC and LOCRC.
About the Study
Data from two large-scale prospective cohorts, the United Kingdom (UK) Biobank (n = 374,568) and the Kailuan cohort based in China (n = 172,809), were obtained. Participants aged 18 years or above were included. Participants with missing data, prior cancer diagnosis, or with outlier blood glucose levels were excluded from the study.
Blood glucose levels were measured using the hexokinase method, and CRC outcomes were tracked through national registries. A range of covariates were assessed, including sociodemographic factors, lifestyle, CRC screening history, and genetic predispositions.
A polygenic risk score (PRS) for blood glucose was calculated using 70 single nucleotide polymorphisms (SNPs) from genome-wide association studies, and non-linear MR analysis was used to explore potential causal relationships between blood glucose and CRC risk, confirming no non-linear associations. Statistical analysis involved the use of Cox proportional hazards models, chi-square test, and Student’s t-test.
Results and Discussion
A total of 4,656 CRC cases were found in the UK Biobank cohort in a median follow-up of 11.8 years, including 357 with EOCRC and 4,299 with LOCRC. A total of 936 CRC cases were recorded in the Kailuan cohort in a median follow-up of 12.1 years, comprising 112 EOCRC cases and 824 LOCRC cases. The incident CRC cases were generally older, male, had lower socioeconomic status, higher body mass index, lower healthy lifestyle indices, and elevated blood glucose levels compared to controls.
After adjusting for confounders, a positive dose-response association was found between blood glucose levels and CRC risk in both cohorts. In the UK Biobank cohort, each 1 mmol/L increase in blood glucose correlated with a 5% increase in CRC risk (hazard ratio [HR] = 1.05), while the Kailuan cohort showed a 4% increase (HR = 1.04).
In the UK Biobank cohort, diabetic blood glucose levels (>7.0 mmol/L) were associated with a 61% increased risk of EOCRC and a 14% increased risk of LOCRC, while the Kailuan cohort showed a 65% increased risk of EOCRC, though this was not statistically significant.
Additionally, no evidence of non-linear causal effects of genetically predicted fasting blood glucose on CRC risk was found across subgroups. The associations held even after excluding cases within the first two years of follow-up and accounting for missing blood glucose values.
The study is strengthened by its comprehensive analysis of the associations between glucose levels and CRC risk across large-scale prospective cohorts, including both linear and non-linear evaluations. However, the study is limited by the small number of EOCRC cases, the limited variance in blood glucose explained by genetic variants, the random collection of blood samples without fasting considerations, and the reliance on a single baseline glucose measurement.
Conclusion
In conclusion, the study found a positive dose-response association between blood glucose levels and CRC risk, especially for EOCRC, with no evidence of a non-linear association. While the mechanisms are not fully understood, the findings highlight the importance of public health initiatives addressing obesity, metabolic dysfunction, and hyperglycemia to reduce the rising incidence of CRC, particularly in the younger population.
These results underscore the importance of age-specific interventions, especially given the rising rates of EOCRC in recent decades.