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. 2023 Jan 16:13:1054132.
doi: 10.3389/fgene.2022.1054132. eCollection 2022.

The role of smoking and alcohol in mediating the effect of gastroesophageal reflux disease on lung cancer: A Mendelian randomization study

Jing Yang  1 , Duorui Nie  2 , Yujing Chen  1 , Zixing Liu  1 , Mengzhao Li  1 , Chun Gong  3 , Qiong Liu  4
Affiliations

The role of smoking and alcohol in mediating the effect of gastroesophageal reflux disease on lung cancer: A Mendelian randomization study

Jing Yang et al. Front Genet. .

Abstract

Observational studies have suggested a positive association between gastroesophageal reflux disease and lung cancer, but due to the existence of confounders, it remains undetermined whether gastroesophageal reflux disease (GERD) has a causal association with lung cancer. Therefore, Mendelian randomization (MR) analyses were applied to investigate the relationship between the two conditions. Two-sample Mendelian randomization analysis was utilized with summary genetic data from the European Bioinformatics Institute (602,604 individuals) and International Lung Cancer Consortium, which provides information on lung cancer and its histological subgroups. Furthermore, we used two-step Mendelian randomization and multivariable Mendelian randomization to estimate whether smoking initiation (311,629 cases and 321,173 controls) and alcohol intake frequency (n = 462,346) mediate any effect of gastroesophageal reflux disease on lung cancer risk. The Mendelian randomization analyses indicated that gastroesophageal reflux disease was associated with and significantly increased the risk of lung cancer (ORIVW = 1.35, 95% CI = 1.18-1.54; p = 1.36 × 10-5). Smoking initiation and alcohol intake frequency mediated 35% and 3% of the total effect of gastroesophageal reflux disease on lung cancer, respectively. The combined effect of these two factors accounted for 60% of the total effect. In conclusion, gastroesophageal reflux disease is associated with an increased risk of lung cancer, and interventions to reduce smoking and alcohol intake may reduce the incidence of lung cancer.

Keywords: Mendelian randomization study; causality; gastroesophageal reflux disease; lung cancer; prospective analysis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Flow chart for the analytical methods and how MR analysis was performed step-by-step.
FIGURE 2
FIGURE 2
Graphical representation of the proposed mediation through mediators for the association of GERD with lung cancer. β1 represents the regression coefficients for the association between GERD and mediators; β2 represents the regression coefficients for the association between mediators and lung cancer; β3 represents the total effect between GERD and lung cancer, without the adjustment for mediators; and β3’ represents the direct effect between GERD and lung cancer, taking into account the adjustment for mediators.
FIGURE 3
FIGURE 3
Odds ratios and p-value of MR analysis for the associations between GERD and lung cancer in the EBI. OR, odds ratio; 95% CI, 95% confidence interval.
See this image and copyright information in PMC

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References

    1. Armstrong R. A. (2014). When to use the Bonferroni correction. Ophthalmic Physiol. Opt. 34 (5), 502–508. 10.1111/opo.12131 - DOI - PubMed
    1. Bathoorn E., Daly P., Gaiser B., Sternad K., Poland C., Macnee W., et al. (2011). Cytotoxicity and induction of inflammation by pepsin in Acid in bronchial epithelial cells. Int. J. Inflam. 2011, 569416. 10.4061/2011/569416 - DOI - PMC - PubMed
    1. Bowden J., Davey Smith G., Burgess S. (2015). Mendelian randomization with invalid instruments: Effect estimation and bias detection through egger regression. Int. J. Epidemiol. 44 (2), 512–525. 10.1093/ije/dyv080 - DOI - PMC - PubMed
    1. Bowden J., Davey Smith G., Haycock P. C., Burgess S. (2016). Consistent estimation in mendelian randomization with some invalid instruments using a weighted median estimator. Genet. Epidemiol. 40 (4), 304–314. 10.1002/gepi.21965 - DOI - PMC - PubMed
    1. Brion M. J., Shakhbazov K., Visscher P. M. (2013). Calculating statistical power in Mendelian randomization studies. Int. J. Epidemiol. 42 (5), 1497–1501. 10.1093/ije/dyt179 - DOI - PMC - PubMed

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