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

IF 7.6 Q1 ONCOLOGY
Chenyu Luo , Jiahui Luo , Yuhan Zhang , Bin Lu , Na Li , Yueyang Zhou , Shuohua Chen , Shouling Wu , Qingsong Zhang , Min Dai , Hongda Chen
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引用次数: 0

Abstract

Background

The incidence of early-onset colorectal cancer (EOCRC), which exhibits differential clinical, pathological, 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.

血糖与早期和晚期结直肠癌的关系:来自两个前瞻性队列和孟德尔随机分析的证据
背景早发结直肠癌(EOCRC)与晚发结直肠癌(LOCRC)相比具有不同的临床、病理和分子特征,其发病率在全球呈上升趋势。本研究分析了英国生物库队列中的 374,568 名参与者和开滦队列中的 172,809 名参与者。使用 Cox 回归模型估计了血糖与 EOCRC/LOCRC 之间的线性关系。限制立方样条(RCS)分析和非线性孟德尔随机化(MR)分析使用了空腹血糖的 70-SNPs 遗传工具,以探索潜在的非线性关联。结果与最低五分位数相比,血糖最高五分位数的参与者的总体 CRC 风险更高(英国生物库队列的 HR = 1.10,95% CI:1.01-1.21,P-趋势 = 0.012;开滦队列的 HR = 1.23,95% CI:1.01-1.51,P-趋势 = 0.036)。在英国生物库队列中,血糖升高(>7.0 mmol/L)与 EOCRC 风险增加(HR = 1.61,95% CI:1.07-2.44)的相关性比与 LOCRC(HR = 1.14,95% CI:1.02-1.27)的相关性更强(P-异质性 = 0.014)。在开滦队列中,血糖升高(7.0 mmol/L)也与 LOCRC 风险增加有关(HR = 1.25,95% CI:1.04-1.65)。结论这项研究表明,血糖与 CRC 风险呈剂量反应式的正相关,尤其是对 EOCRC 而言。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
14.20
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