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

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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.

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Data availability

Some or all data generated or analyzed were all publicly available.

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Acknowledgements

The authors thank all investigators of the IEU OpenGwas project. The GWAS data used in our study were downloaded from https://gwas.mrcieu.ac.uk/datasets.

Funding

The study was funded by Health Commission of Shanxi Province (Grant no. 2022073).

Author information

Author notes

  1. Hongqiang Chai, Fei Li & Ming Wu

    Present address: Fifth hospital of Shanxi Medical University (Shanxi Provincial People′s Hospital), Urology, Taiyuan, Shanxi, China

  2. Lei Pang & Weibing Shuang

    Present address: First Clinical Medical College of Shanxi Medical University, Urology, Taiyuan, Shanxi, China

  3. Zijun Ding

    Present address: Shanxi children′s Hospital, Neonatology, Taiyuan, Shanxi, China

Authors and Affiliations

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

    Lei Pang

  2. First Hospital of Shanxi Medical University, Shanxi, China

    Weibing Shuang

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  1. Lei Pang
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Correspondence to Weibing Shuang.

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Lei Pang, Zijun Ding, Hongqiang Chai, Fei Li, Ming Wu and Weibing Shuang declare that they have no conflict of interest.

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Pang, L., Ding, Z., Chai, H. et al. Causal relationship between smoking status, smoking frequency and bladder cancer: a Mendelian randomization study. Genes Genom 45, 203–213 (2023). https://doi.org/10.1007/s13258-022-01346-6

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  • DOI: https://doi.org/10.1007/s13258-022-01346-6

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