Associations between blood glucose and early- and late-onset colorectal cancer: evidence from two prospective cohorts and Mendelian randomization analyses  

作　　者：Chenyu Luo Jiahui Luo Yuhan Zhang Bin Lu Na Li Yueyang Zhou Shuohua Chen Shouling Wu Qingsong Zhang Min Dai Hongda Chen 

机构地区：[1]Department of Cancer Epidemiology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China [2]Center for Prevention and Early Intervention,National Infrastructures for Translational Medicine,Institute of Clinical Medicine,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing,China [3]Cardiology Department,Kailuan General Hospital,Tangshan,China [4]Department of General Surgery,Kailuan General Hospital,Tangshan,China

出　　处：《Journal of the National Cancer Center》2024年第3期241-248,共8页癌症科学进展（英文）

基　　金：funded by the Chinese Academy of Medical Science Innovation Fund for Medical Science(grant number:2022-I2M-1-0031);the National Natural Science Foundation of China(grant number:82173606);supported by the Beijing Nova Program of Science and Technology(grant number:20230484397);the Na-tional Natural Science Foundation of China(grant number:82273726).

摘　　要：Background: The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, patho- logical, and molecular features compared to late-onset CRC (LOCRC), is rising globally. The potential differential effects of blood glucose on EOCRC compared to LOCRC have not been investigated. Methods: This study analyzed 374,568 participants from the UK Biobank cohort and 172,809 participants from the Kailuan cohort. The linear associations between blood glucose and EOCRC/LOCRC were estimated using Cox regression models. Restricted cubic spline (RCS) analysis and non-linear Mendelian randomization (MR) analysis using a 70-SNPs genetic instrument for fasting glucose were used to explore the potential non-linear associations. Results: Participants in the highest quintile of blood glucose had higher overall CRC risk compared to the lowest quintile (HR = 1.10 in the UK Biobank cohort, 95% CI: 1.01-1.21, P -trend = 0.012;HR = 1.23 in the Kailuan cohort, 95% CI: 1.01-1.51, P -trend = 0.036). Elevated glucose ( > 7.0 mmol/L) was more strongly associated with increased risk of EOCRC (HR = 1.61, 95% CI: 1.07-2.44) than with LOCRC (HR = 1.14, 95% CI: 1.02-1.27) in the UK Biobank cohort ( P- heterogeneity = 0.014). Elevated glucose ( > 7.0 mmol/L) was associated with increased risk of LOCRC (HR = 1.25, 95% CI: 1.04-1.65) in the Kailuan cohort as well. There was no evidence for non-linear associations between blood glucose and risks of EOCRC/LOCRC. Conclusions: This study showed a positive association between blood glucose and CRC risk in a dose-response manner, particularly for EOCRC, suggesting that tighter glucose control should be a priority for younger age groups.

关 键 词：Colorectal cancer Early-onset colorectal cancer GLUCOSE Mendelian randomization Cancer prevention 

分 类 号：R73[医药卫生—肿瘤]