PDF(Pubmed)
Abstract：
The purpose of this study was to investigate the causal association between unhealthy lifestyle style factors and the risk of colorectal cancer, with the aim of preventing the occurrence of colorectal cancer by modifying unhealthy lifestyles. A two-sample Mendelian randomization (MR) approach was employed in this study, utilizing the inverse-variance weighted method as the primary research method. This MR analysis analyzed data of 3022 colorectal cancer cases and 174,006 controls from the FinnGen database. Single nucleotide polymorphisms (SNPs) associated with unhealthy lifestyle factors were selected as instrumental variables (IVs), including two obesity-related indicators, BMI (body mass index) and WHR (waist-to-hip ratio). Four phenotypes of smoking (smoking initiation, ever smoked, smoking per day, smoking cessation) and one phenotype of alcohol consumption (drinks per week). Four phenotypes of physical activity (accelerometer-based physical activity, moderate-to-vigorous physical activity, vigorous physical activity, strenuous sports or other exercises). All SNPs were obtained from published genome-wide association studies. The study found that the obesity-related indicator, higher WHR (OR = 1.38, 95% CI 1.12-1.70; P = 0.002) were associated with an increased risk of colorectal cancer, and two smoking phenotypes, cigarettes per day(OR = 1.30, 95% CI 1.01-1.68; P = 0.042)and smoking initiation (OR = 3.48, 95% CI 1.15-10.55; P = 0.028), were potentially associated with an increased risk of colorectal cancer. However, there was no evidence to suggest that physical activities and alcohol consumption were associated with colorectal cancer (all p > 0.05). In addition, the study detected no pleiotropy (all p > 0.05). This MR analysis indicates a causal association between a higher waist-to-hip ratio and the risk of colorectal cancer and a suggestive association between smoking and the risk of colorectal cancer among Europeans. These findings contribute to the understanding of the etiology of colorectal cancer and have potential implications for its prevention.
摘要：
这项研究的目的是调查不健康的生活方式因素与结直肠癌风险之间的因果关系。目的是通过改变不健康的生活方式来预防结直肠癌的发生。本研究采用了双样本孟德尔随机化(MR)方法，采用方差逆加权法作为主要研究方法。该MR分析分析了来自FinnGen数据库的3022例结肠直肠癌病例和174,006例对照的数据。选择与不健康生活方式因素相关的单核苷酸多态性（SNP）作为工具变量（IVs），包括两个与肥胖相关的指标，BMI（体重指数）和WHR（腰臀比）。吸烟的四种表型(吸烟开始，曾经吸烟，每天吸烟,戒烟)和一种饮酒表型(每周饮酒)。身体活动的四种表型（基于加速度计的身体活动，中等到剧烈的体力活动，剧烈的体力活动，剧烈运动或其他运动)。所有SNP均获自已发表的全基因组关联研究。研究发现，与肥胖相关的指标，高WHR(OR=1.38,95%CI1.12-1.70;P=0.002)与结直肠癌风险增加相关,和两种吸烟表型，每天吸烟（OR=1.30，95％CI1.01-1.68；P=0.042）和开始吸烟（OR=3.48，95％CI1.15-10.55；P=0.028），可能与结直肠癌风险增加有关。然而,没有证据表明体力活动和饮酒与结直肠癌相关(均P>0.05).此外,该研究未检测到多效性(均p>0.05)。这项MR分析表明，在欧洲人中，较高的腰臀比与结直肠癌的风险之间存在因果关系，而吸烟与结直肠癌的风险之间存在因果关系。这些发现有助于了解结直肠癌的病因，并对其预防具有潜在意义。
