Nutrition and Metabolism Branch, International Agency for Research on Cancer, Lyon, France.
MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK.
BMC Med. 2023 Jan 4;21(1):5. doi: 10.1186/s12916-022-02702-9.
Observational studies have linked childhood obesity with elevated risk of colorectal cancer; however, it is unclear if this association is causal or independent from the effects of obesity in adulthood on colorectal cancer risk.
We conducted Mendelian randomization (MR) analyses to investigate potential causal relationships between self-perceived body size (thinner, plumper, or about average) in early life (age 10) and measured body mass index in adulthood (mean age 56.5) with risk of colorectal cancer. The total and independent effects of body size exposures were estimated using univariable and multivariable MR, respectively. Summary data were obtained from a genome-wide association study of 453,169 participants in UK Biobank for body size and from a genome-wide association study meta-analysis of three colorectal cancer consortia of 125,478 participants.
Genetically predicted early life body size was estimated to increase odds of colorectal cancer (odds ratio [OR] per category change: 1.12, 95% confidence interval [CI]: 0.98-1.27), with stronger results for colon cancer (OR: 1.16, 95% CI: 1.00-1.35), and distal colon cancer (OR: 1.25, 95% CI: 1.04-1.51). After accounting for adult body size using multivariable MR, effect estimates for early life body size were attenuated towards the null for colorectal cancer (OR: 0.97, 95% CI: 0.77-1.22) and colon cancer (OR: 0.97, 95% CI: 0.76-1.25), while the estimate for distal colon cancer was of similar magnitude but more imprecise (OR: 1.27, 95% CI: 0.90-1.77). Genetically predicted adult life body size was estimated to increase odds of colorectal (OR: 1.27, 95% CI: 1.03, 1.57), colon (OR: 1.32, 95% CI: 1.05, 1.67), and proximal colon (OR: 1.57, 95% CI: 1.21, 2.05).
Our findings suggest that the positive association between early life body size and colorectal cancer risk is likely due to large body size retainment into adulthood.
观察性研究表明，儿童肥胖与结直肠癌风险升高有关；然而，目前尚不清楚这种关联是否具有因果关系，或者是否独立于成年后肥胖对结直肠癌风险的影响。
我们进行了孟德尔随机化（MR）分析，以研究儿童早期（10 岁）自我感知的体型（较瘦、较胖或中等）和成年时测量的体重指数（平均年龄 56.5 岁）与结直肠癌风险之间的潜在因果关系。使用单变量和多变量 MR 分别估计体型暴露的总效应和独立效应。汇总数据来自 UK Biobank 对 453,169 名参与者的体型进行的全基因组关联研究，以及对三个结直肠癌联盟的 125,478 名参与者进行的全基因组关联研究荟萃分析。
遗传预测的儿童早期体型估计会增加结直肠癌的发病几率（每类别变化的比值比 [OR]：1.12，95%置信区间 [CI]：0.98-1.27），结肠癌（OR：1.16，95% CI：1.00-1.35）和远端结肠癌（OR：1.25，95% CI：1.04-1.51）的结果更强。在用多变量 MR 考虑成年后体型后，早期体型的效应估计值向结直肠癌（OR：0.97，95% CI：0.77-1.22）和结肠癌（OR：0.97，95% CI：0.76-1.25）的零值减弱，而远端结肠癌的估计值则相似但更不精确（OR：1.27，95% CI：0.90-1.77）。遗传预测的成年体型估计会增加结直肠癌（OR：1.27，95% CI：1.03，1.57）、结肠癌（OR：1.32，95% CI：1.05，1.67）和近端结肠癌（OR：1.57，95% CI：1.21，2.05）的发病几率。
我们的研究结果表明，儿童早期体型与结直肠癌风险之间的正相关关系可能是由于成年后体型较大。
