Gao Lingling, Di Xiaoling, Gao Lulu, Liu Zhanhui, Hu Fengping
Department of Medical Laboratory, The First Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Gland Surgery, People's Hospital of Dingzhou, Dingzhou, China.
J Gastrointest Oncol. 2023 Apr 29;14(2):798-805. doi: 10.21037/jgo-23-134.
Frailty is closely related to cancer. Previous research has shown that cancer patients are prone to frailty, and frailty increases the risk of adverse outcomes in cancer patients. However, it is unclear whether frailty increases the risk of cancer. This 2-sample Mendelian-randomization (MR) study sought to analyze the relationship between frailty and the risk of colon cancer.
The database was extracted from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) in 2021. The genome-wide association study (GWAS) data related to colon cancer was obtained from the GWAS website (http://gwas.mrcieu.ac.uk/datasets), involving 462,933 individuals' gene information. Single-nucleotide polymorphisms (SNPs) were defined as the instrumental variables (IVs). The SNPs closely associated with the Frailty Index at a genome-wide significance level were selected. To further screen the IVs, we selected the confounding factors using the PhenoScanner (http://www.phenoscanner.medschl.cam.ac.uk/phenoscanner). To estimate the causal effect of the Frailty Index on colon cancer, the MR-Egger regression, weighted median (WM1), inverse-variance weighted (IVW), and weight mode (WM2) methods were applied to calculate the SNP-frailty index and the SNP-cancer estimates. Cochran's Q statistic was used to estimate heterogeneity. The two-sample Mendelian randomization (TSMR) analysis was performed using the "TwoSampleMR" and "plyr" packages. All the statistical tests were 2-tailed, and a P value <0.05 was considered statistically significant.
We selected 8 SNPs as the IVs. The results of the IVW analysis [odds ratio (OR) =0.995, 95% confidence interval (CI): 0.990-1.001, P=0.052] showed that the genetic changes in the Frailty Index were not statistically associated with the risk of colon cancer, and no significant heterogeneity between these 8 genes was observed (Q =7.382, P=0.184). The MR-Egger (OR =0.987, 95% CI: 0.945-1.031, P=0.581), WM1 (OR =0.995, 95% CI: 0.990-1.001, P=0.118), WM2 (OR =0.996, 95% CI: 0.988-1.004, P=0.356), and SM (OR =0.996, 95% CI: 0.987-1.005, P=0.449) results were also consistent with each other. The sensitivity analysis based on the leave-one-out method showed that the individual SNPs did not affect the robustness of the results.
Frailty might have no effect on the risk of colon cancer.
衰弱与癌症密切相关。先前的研究表明，癌症患者容易出现衰弱，而衰弱会增加癌症患者不良结局的风险。然而，尚不清楚衰弱是否会增加患癌风险。这项两样本孟德尔随机化（MR）研究旨在分析衰弱与结肠癌风险之间的关系。
数据库于2021年从医学研究理事会综合流行病学单位（MRC - IEU）提取。与结肠癌相关的全基因组关联研究（GWAS）数据从GWAS网站（http://gwas.mrcieu.ac.uk/datasets）获取，涉及462,933个人的基因信息。单核苷酸多态性（SNP）被定义为工具变量（IV）。选择在全基因组显著水平上与衰弱指数密切相关的SNP。为了进一步筛选IV，我们使用PhenoScanner（http://www.phenoscanner.medschl.cam.ac.uk/phenoscanner）选择混杂因素。为了估计衰弱指数对结肠癌的因果效应，应用MR - Egger回归、加权中位数（WM1）、逆方差加权（IVW）和权重模式（WM2）方法来计算SNP - 衰弱指数和SNP - 癌症估计值。使用Cochran's Q统计量来估计异质性。使用“TwoSampleMR”和“plyr”软件包进行两样本孟德尔随机化（TSMR）分析。所有统计检验均为双侧检验，P值<0.05被认为具有统计学意义。
我们选择了8个SNP作为IV。IVW分析结果[比值比（OR）=0.995，95%置信区间（CI）：0.990 - 1.001，P = 0.052]表明，衰弱指数的基因变化与结肠癌风险无统计学关联，并且在这8个基因之间未观察到显著异质性（Q = 7.382，P = 0.184）。MR - Egger（OR = 0.987，95% CI：0.945 - 1.031，P = 0.581）、WM1（OR = 0.995，95% CI：0.990 - 1.001，P = 0.118）、WM2（OR = 0.996，95% CI：0.988 - 1.004，P = 0.356）和SM（OR = 0.996，95% CI：0.987 - 1.005，P = 0.449）结果也相互一致。基于留一法的敏感性分析表明，单个SNP不影响结果的稳健性。
衰弱可能对结肠癌风险没有影响。
