Education and lung cancer: a Mendelian randomization study

Abstract

Background

We aimed to investigate whether more years spent in education are causally associated with a lower risk of lung cancer, through a two-sample Mendelian randomization study.

Methods

The main analysis used publicly available genetic summary data from two large consortia [International Lung Cancer Consortium (ILCCO) and Social Science Genetic Association Consortium (SSGAC)]. Genetic variants used as instrumental variables for years of education were derived from SSGAC. Finally, genetic data from three additional consortia (TAG, GLGC, GIANT) were analysed to investigate whether education could causally alter common lung cancer risk factors. The exposure was the genetic predisposition to higher levels of education, measured by 73 single nucleotide polymorphisms from SSGAC. The primary outcome was the risk of lung cancer (11 348 events in ILCCO). Secondary outcomes based on different histological subtypes were also examined. Analyses were performed using the package TwoSampleMR in R.

Results

Genetic predisposition towards 3.6  years of additional education was associated with a 52% lower risk of lung cancer (odds ratio 0.48, 95% confidence interval 0.34 to 0.66; P = 1.02 × 10 − 5). Sensitivity analyses were consistent with a causal interpretation in which major bias from genetic pleiotropy was unlikely. The Mendelian randomization assumptions did not seem to be violated. Genetic predisposition towards longer education was additionally associated with less smoking, lower body mass index and a favourable blood lipid profile.

Conclusions

Our study indicated that low education is a causal risk factor in the development of lung cancer. Further work is needed to elucidate the potential mechanisms.

调查受教育年限越长是否与肺癌风险越低有因果关系。

MR分析分为exposure和outcome, 通过使用与exposure相关的工具变量SNP，调查exposure和outcome的因果关系。

主要使用了国际肺癌联盟(ILCCO)和社会科学遗传协会联盟(SSGAC)]提供的公开遗传摘要数据。教育的工具变量来自SSGAC的研究，共有73个SNP。最后，分析了来自另外三个联盟(TAG, GLGC, GIANT)的基因数据，以调查教育是否可以导致肺癌的常见危险因素的改变。主要的outcome是肺癌的风险(ILCCO的11348例事件)。

接受3.6年额外教育的遗传倾向与肺癌风险降低52%相关。敏感性分析与不太可能出现遗传多效性的重大偏差的因果解释一致。违背孟德尔随机化假设的可能性不大。受教育时间较长的遗传倾向还与较少吸烟、较低的体重指数和良好的血脂状况有关。

研究表明，受教育程度低是肺癌发生的一个危险因素。需要进一步的工作来阐明潜在的机制。

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