Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.
EBioMedicine. 2024 Mar;101:105010. doi: 10.1016/j.ebiom.2024.105010. Epub 2024 Feb 12.
Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain.
We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO).
A 1-standard deviation (SD:5.1 kg/m) increment in BMI levels was found to increase risks of Jass type 1 (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10) and Jass type 2 CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4 CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3 (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03).
Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4).
Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.
肥胖与结直肠癌（CRC）的大多数分子亚型呈正相关；然而，这些关联的程度和因果关系尚不确定。
我们使用孟德尔随机化（MR）来检查体型特征（体重指数[BMI]、腰围和体脂百分比）与 Jass 分类类型和 CRC 的个体亚型（微卫星不稳定性[MSI]状态、CpG 岛甲基化表型[CIMP]状态、BRAF 和 KRAS 突变）风险之间的潜在因果关系。肿瘤标志物的汇总数据来自两个遗传联合体（CCFR、GECCO）。
发现 BMI 水平增加 1 个标准差（SD：5.1kg/m），Jass 1 型（比值比[OR]：2.14，95%置信区间[CI]：1.46，3.13；p 值=9×10）和 Jass 2 型 CRC（OR：2.20，95%CI：1.26，3.86；p 值=0.005）的风险增加。与 Jass 4 型 CRC 相比，这些关联的程度更强（p-差异：分别为 0.03 和 0.04）。腰围增加 1 个标准差（SD：13.4cm），Jass 3 型（OR 1.73，95%CI：1.34，2.25；p 值=9×10）的风险增加，与 Jass 4 型 CRC 相比，这一风险更强（p-差异：0.03）。体脂百分比较高（SD：8.5%）增加了 Jass 1 型 CRC（OR：2.59，95%CI：1.49，4.48；p 值=0.001）的风险，与 Jass 4 型 CRC 相比，这一风险更大（p-差异：0.03）。
与传统途径（Jass 4 型）相比，体型与锯齿状（Jass 1 型和 2 型）和替代（Jass 3 型）CRC 发生途径的关系更为密切。
英国癌症研究中心、英国国家卫生研究院、医学研究理事会、美国国立卫生研究院、美国国家癌症研究所、美国癌症研究所、布莱根妇女医院、预防癌症基金会、维多利亚癌症局、瑞典研究理事会、瑞典癌症协会、韦斯特博滕地区、克努特和爱丽丝·沃伦伯格基金会、狮子癌症研究基金会、捐赠基金、于默奥大学。完整的资助详情见致谢。
