为了确定胰岛素受体（IR）在结直肠癌发生中的作用，我们根据IR的表达水平研究了身高、体重指数（BMI）和体力活动与结直肠癌（CRC）和两种CRC亚型的关系。我们利用了一项大规模、基于人群的前瞻性队列研究的数据，该研究对日本秋田县和冲绳县的 18,158 名中老年受试者进行了研究。在统计分析中，我们使用 Cox 比例风险模型以及估计风险比 (HR) 和 95% 置信区间 (CI) 来评估 CRC 及其亚型的风险（通过 IRβ（IR 的跨膜亚基）的免疫组织化学定义）。在 IRβ 定义的亚型中，身高与 IRβ 阳性结直肠癌的风险没有明显关联。相比之下，BMI≥30.0kg/m2（即肥胖）的IRβ阳性CRC的多变量HR为1.77（95%CI=≥1.04-3.03），而BMI<25.0kg/m2则为1.77。此外，体力活动的增加与 IRβ 阳性 CRC 风险的降低显着相关（每 5 MET 小时/天的多变量 HR = 0.93，95% CI = 0.88-0.99）。同时，我们发现任何暴露与 IRβ 阴性 CRC 之间没有显着关联。同样，CRC 两种亚型之间的异质性也不具有统计学意义。这些发现表明，肥胖和体力活动分别对表达 IR 的 CRC 的发展产生促进和抑制作用。© 2024 UICC。

To ascertain the involvement of insulin receptors (IRs) in colorectal carcinogenesis, we investigated the association of height, body mass index (BMI), and physical activity with colorectal cancer (CRC) and two subtypes of CRC according to the expression level of IR. We utilized data from a large-scale, population-based prospective cohort study of 18,158 middle-aged and elderly subjects in Akita and Okinawa, Japan. In the statistical analysis, we used the Cox proportional hazards model and estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of CRC and its subtypes as defined by immunohistochemistry of IRβ, a transmembrane subunit of IR. In the IRβ-defined subtypes, height showed no apparent association with the risk of IRβ-positive CRC. In contrast, a multivariable HR of IRβ-positive CRC was 1.77 (95% CI = 1.04-3.03) with a BMI of ≥30.0 kg/m2 (i.e., obesity), compared to a BMI of <25.0 kg/m2. Further, an increase in physical activity was significantly associated with decreased risk of IRβ-positive CRC (multivariable HR per 5 METs-hour/day = 0.93, 95% CI = 0.88-0.99). Meanwhile, we found no significant association between any exposure and IRβ-negative CRC. Likewise, heterogeneity between the two subtypes of CRC was not statistically significant. These findings imply that obesity and physical activity exert promoting and suppressing effects on the development of CRC expressing IRs, respectively.© 2024 UICC.