Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, Germany.
Medical Faculty Heidelberg, University of Heidelberg, Heidelberg, Germany.
Am J Clin Nutr. 2020 Mar 1;111(3):562-569. doi: 10.1093/ajcn/nqz315.
Observational studies have consistently shown that a high BMI is associated with increased risk of colorectal cancer (CRC). However, the underlying mechanisms linking obesity to CRC remain unclear.
To investigate the associations of BMI and CRC by major molecular pathological subtypes of CRC.
This analysis included 2407 cases and 2454 controls from a large German population-based case-control study. Information on recent weight and height as well as other demographic and lifestyle data were obtained by standardized interviews. Multinomial logistic regression was used to estimate ORs and 95% CIs for the associations between BMI and risk of CRC by major molecular pathological features: microsatellite instability (MSI), CpG island methylator phenotype (CIMP), B-Raf proto-oncogene serine/threonine kinase (BRAF) mutation, and Kirsten rat sarcoma viral oncogene homolog gene (KRAS) mutation.
Among women, a higher BMI was differentially and more strongly associated with risk of MSI CRC (OR per 5 kg/m2: 1.69; 95% CI: 1.34, 2.12; Pheterogeneity ≤ 0.001), CIMP-high CRC (OR per 5 kg/m2: 1.57; 95% CI: 1.30, 1.89; Pheterogeneity ≤ 0.001), BRAF-mutated CRC (OR per 5 kg/m2: 1.56; 95% CI: 1.22, 1.99; Pheterogeneity = 0.04), and KRAS-wildtype CRC (OR per 5 kg/m2: 1.35; 95% CI: 1.17, 1.54; Pheterogeneity = 0.01), compared with the risk of CRC in subjects with the molecular feature counterpart. In men, no meaningful differences in CRC risk were observed for the investigated molecular feature pairs. For the association of BMI with MSI CRC, we observed effect modification by sex (Pinteraction = 0.04). Also, in women, the risk of CRC with the serrated pathway features was more strongly increased with higher BMI than risk of CRC with the traditional pathway features (OR per 5 kg/m2: 1.73; 95% CI: 1.28, 2.34; Pheterogeneity = 0.01).
In women, the relation between BMI and MSI-high CRC seems to be stronger than that between BMI and microsatellite-stable CRC. However, a validation in an independent cohort is needed. This observational study was registered at the German Clinical Trials Register (http://www.drks.de; study ID: DRKS00011793), an approved primary register in the WHO network.
观察性研究一致表明，较高的 BMI 与结直肠癌（CRC）风险增加相关。然而，肥胖与 CRC 之间的潜在机制仍不清楚。
通过 CRC 的主要分子病理亚型研究 BMI 与 CRC 之间的关联。
本分析包括来自一项大型德国基于人群的病例对照研究的 2407 例病例和 2454 例对照。通过标准化访谈获得近期体重和身高以及其他人口统计学和生活方式数据的信息。多变量逻辑回归用于估计 BMI 与主要分子病理特征（微卫星不稳定性（MSI）、CpG 岛甲基化表型（CIMP）、B-Raf 原癌基因丝氨酸/苏氨酸激酶（BRAF）突变和 Kirsten 大鼠肉瘤病毒致癌基因同源物基因（KRAS）突变）之间 CRC 风险的比值比（OR）和 95%置信区间（CI）。
在女性中，较高的 BMI 与 MSI CRC（每 5kg/m2 的 OR：1.69；95%CI：1.34，2.12；P 异质性≤0.001）、CIMP 高 CRC（每 5kg/m2 的 OR：1.57；95%CI：1.30，1.89；P 异质性≤0.001）、BRAF 突变 CRC（每 5kg/m2 的 OR：1.56；95%CI：1.22，1.99；P 异质性=0.04）和 KRAS 野生型 CRC（每 5kg/m2 的 OR：1.35；95%CI：1.17，1.54；P 异质性=0.01）的风险之间存在差异且更强的关联，而与具有分子特征对应的 CRC 风险相比。在男性中，对于所研究的分子特征对，CRC 风险没有观察到有意义的差异。对于 BMI 与 MSI CRC 的关联，我们观察到性别存在交互作用（P 交互=0.04）。此外，在女性中，较高 BMI 与锯齿状通路特征相关的 CRC 风险比与传统通路特征相关的 CRC 风险增加更强（每 5kg/m2 的 OR：1.73；95%CI：1.28，2.34；P 异质性=0.01）。
在女性中，BMI 与 MSI 高 CRC 之间的关系似乎比 BMI 与微卫星稳定 CRC 之间的关系更强。然而，需要在独立队列中进行验证。这项观察性研究在德国临床试验注册处（http://www.drks.de；研究 ID：DRKS00011793）进行了注册，这是世卫组织网络中的一个经批准的主要注册处。
