Cigarette smoking and thyroid cancer risk: A Mendelian randomization study

• Published in: Cancer medicine (Malden, MA) Vol. 12; no. 19; pp. 19866 - 19873
• Main Authors: Jiang, Hongzhan, Li, Yi, Shen, Jiali, Lin, Huihui, Fan, Siyue, Qiu, Rongliang, He, Jiaxi, Lin, Ende, Chen, Lijuan
• Format: Journal Article
• Language: English
• Published: Bognor Regis John Wiley & Sons, Inc 01-10-2023; John Wiley and Sons Inc; Wiley
• Subjects: causality; Cigarette smoking; Cigarettes; Cohort analysis; Estimates; Genetic diversity; Genome-wide association studies; Genomes; Malignancy; Mendelian randomization; Methods; Phenotypes; Pleiotropy; Sensitivity analysis; Smoking; Statistics; Thyroid cancer; Tobacco; Tobacco smoking; Tumors; Variables; United States > US
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.6570

Background
The association between cigarette smoking and thyroid cancer has been reported in prospective cohort studies, but the relationship remains controversial. To investigate this potential correlation further, we employed Mendelian randomization methodology to evaluate the causative impact of smoking on thyroid cancer incidence.
Methods
From the genome‐wide association study and Sequencing Consortium of Alcohol and Nicotine use, we obtained genetic variants associated with smoking initiation and cigarettes per day (1.2 million individuals). We also extracted genetic variants associated with past tobacco smoking from the UK Biobank (424,960 individuals). Thyroid cancer outcomes were selected from the FinnGen GWAS (989 thyroid cancer cases and 217,803 control cases). Sensitivity analyses employing various approaches such as weighted median, MR‐Egger, and MR‐pleiotropy residual sum and outlier (MR‐PRESSO) have been executed, as well as leave‐one‐out analysis to identify pleiotropy.
Results
Using the IVW approach, we did not find evidence that any of the three smoking phenotypes were related to thyroid cancer (smoking initiation: odds ratio (OR) = 1.56, p = 0.61; cigarettes per day: OR = 0.85, p = 0.51; past tobacco smoking: OR = 0.80, p = 0.78). The heterogeneity (p > 0.05) and pleiotropy (p > 0.05) testing provided confirmatory evidence for the validity of our MR estimates.
Conclusions
The MR analysis revealed that there may not exist a causative link between smoking exposure and elevated incidence rates of thyroid malignancies.
We used Mendelian randomization analysis to evaluate the causal relationship between smoking and thyroid cancer, and found that smoking was not associated with thyroid cancer.