吸烟状况、吸烟频率与膀胱癌之间的因果关系：一项孟德尔随机化研究。

Causal relationship between smoking status, smoking frequency and bladder cancer: a Mendelian randomization study.

机构信息

Fifth hospital of Shanxi Medical University (Shanxi Provincial People's Hospital), Urology, Taiyuan, Shanxi, China.

First Clinical Medical College of Shanxi Medical University, Urology, Taiyuan, Shanxi, China.

出版信息

Genes Genomics. 2023 Feb;45(2):203-213. doi: 10.1007/s13258-022-01346-6. Epub 2022 Dec 12.

DOI:10.1007/s13258-022-01346-6

PMID:36508086

Abstract

BACKGROUND

Smoking is a well-established risk factor for bladder cancer. However, it remained unclear that whether smoke status and smoke frequency increase bladder cancer.

OBJECTIVE

We aim to explore the causal relationship between smoking status, smoking frequency and the risk of bladder cancer by Mendelian randomization.

METHODS

Large sample size of the genome-wide association(GWAS) database of smoking status, smoking frequency and bladder cancer were obtained. Smoking status included never, previous and current whereas smoking frequency included cigarettes smoked per day, number of cigarettes currently smoked daily and pack years of smoking. Six sets of instrumental variables and 78 related single nucleotide polymorphic(SNP) loci were identified (P < 5 × 10-8. Linkage disequilibrium R2 < 0.001). The causal relationship between smoking status and bladder tumor was studied by inverse variance weighted (IVW), weighted median and MR-Egger regression. Sensitivity analysis were also performed.

RESULTS

There is no causal effect from smoke status on bladder cancer risk while significantly positive relationship between smoking frequency on bladder cancer risk were found. IVW results showed that cigarettes smoked per day, number of cigarettes currently smoked daily and pack years of smoking increase bladder cancer (OR 1.001, 95% CI 1.000-1.002, P = 0.047; OR 1.003, 95% CI 1.000-1.005, P = 0.028; OR 1.004, 95% CI 1.001-1.006, P = 0.003). Sensitivity analysis showed that genetic pleiotropy did not bias the results.

CONCLUSION

The results of two sample Mendelian randomization analysis show that there is a positive causal relationship between smoking frequency and the risk of bladder cancer.

摘要

背景

吸烟是膀胱癌的一个既定危险因素。然而，吸烟状况和吸烟频率是否会增加膀胱癌风险仍不清楚。

目的

我们旨在通过孟德尔随机化方法探讨吸烟状况、吸烟频率与膀胱癌风险之间的因果关系。

方法

从吸烟状况、吸烟频率和膀胱癌的全基因组关联（GWAS）数据库中获取了大量样本。吸烟状况包括从不吸烟、以前吸烟和现在吸烟，吸烟频率包括每天吸烟支数、目前每天吸烟支数和吸烟包年数。确定了 6 组工具变量和 78 个相关单核苷酸多态性（SNP）位点（P<5×10-8，连锁不平衡 R2<0.001）。通过逆方差加权（IVW）、加权中位数和 MR-Egger 回归研究吸烟状况与膀胱癌肿瘤之间的因果关系。还进行了敏感性分析。

结果

吸烟状况与膀胱癌风险之间没有因果关系，而吸烟频率与膀胱癌风险之间存在显著的正相关关系。IVW 结果表明，每天吸烟支数、目前每天吸烟支数和吸烟包年数增加膀胱癌风险（OR 1.001，95%CI 1.000-1.002，P=0.047；OR 1.003，95%CI 1.000-1.005，P=0.028；OR 1.004，95%CI 1.001-1.006，P=0.003）。敏感性分析表明遗传多效性不会影响结果。