Evaluating the effect of metabolic traits on oral and oropharyngeal cancer risk using Mendelian randomization.
Evaluating the effect of metabolic traits on oral and oropharyngeal cancer risk using Mendelian randomization.
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作者：
Gormley M;Dudding T;Thomas SJ;Tyrrell J;Ness AR;Pring M;Legge D;Davey Smith G;Richmond RC;Vincent EE;Bull C
世界卫生组织最近的一份报告指出，至少40%的癌症病例是可以预防的，吸烟、饮酒和肥胖被认为是最重要的三个可改变的生活方式因素。鉴于吸烟率的显著下降，特别是在发达国家，其他可能改变的头颈癌风险因素值得调查。在多项观察性研究中，肥胖和相关代谢紊乱（如2型糖尿病（T2D）和高血压）与头颈癌风险相关。然而，肥胖也与吸烟有关，有偏差、混淆或反向因果关系可能解释这些发现。为了克服观察性研究的挑战，我们在全基因组关联研究（GWAS）中使用与肥胖、血糖和血压性状密切相关的遗传变异进行了双样本孟德尔随机化（逆方差加权[IVW]方法）。结果数据来自6034例口腔和口咽病例的最大可用GWAS，对照组为6585例。我们发现有限的证据表明遗传代理体重指数（BMI; OR IVW = 0.89, 95% CI = 0.72-1.09, p = 0.26 / 1 BMI标准差[4.81kg/m2]）对口腔癌和口咽癌风险的因果影响。同样，T2D和高血压等相关特征的证据也很有限。由于目前可用的GWAS缺乏检测它们的能力，因此不能排除小的影响。
A recent World Health Organization report states that at least 40% of all cancer cases may be preventable, with smoking, alcohol consumption, and obesity identified as three of the most important modifiable lifestyle factors. Given the significant decline in smoking rates, particularly within developed countries, other potentially modifiable risk factors for head and neck cancer warrant investigation. Obesity and related metabolic disorders such as type 2 diabetes (T2D) and hypertension have been associated with head and neck cancer risk in multiple observational studies. However, adiposity has also been correlated with smoking, with bias, confounding or reverse causality possibly explaining these findings. To overcome the challenges of observational studies, we conducted two-sample Mendelian randomization (inverse variance weighted [IVW] method) using genetic variants which were robustly associated with adiposity, glycaemic and blood pressure traits in genome-wide association studies (GWAS). Outcome data were taken from the largest available GWAS of 6034 oral and oropharyngeal cases, with 6585 controls. We found limited evidence of a causal effect of genetically proxied body mass index (BMI; OR IVW = 0.89, 95% CI 0.72–1.09, p = 0.26 per 1 standard deviation in BMI [4.81kg/m2]) on oral and oropharyngeal cancer risk. Similarly, there was limited evidence for related traits including T2D and hypertension. Small effects cannot be excluded given the lack of power to detect them in currently available GWAS.