Thyroid dysfunction and risk of cutaneous malignant melanoma: a bidirectional two-sample Mendelian randomization study

Hua Dong; Lei Pan; Yanhui Shen; Qinxuan Xu; Jinyu Hu; Zhiwei Hu; Yuchang Fei

doi:10.3389/fendo.2023.1239883

Thyroid dysfunction and risk of cutaneous malignant melanoma: a bidirectional two-sample Mendelian randomization study

Front Endocrinol (Lausanne). 2023 Nov 29:14:1239883. doi: 10.3389/fendo.2023.1239883. eCollection 2023.

Authors

Hua Dong^#¹, Lei Pan^#², Yanhui Shen³, Qinxuan Xu², Jinyu Hu², Zhiwei Hu¹, Yuchang Fei⁴

Affiliations

¹ Endocrinology Department, Jiashan Hospital Affiliated of Jiaxing University, The First People's Hospital of Jiashan, Jiaxing, Zhejiang, China.
² Department of Oncology, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China.
³ Department of Traditional Chinese Medicine, Institute for Food, Drug and Product Quality Control of Jiaxing, Jiaxing, Zhejiang, China.
⁴ Department of Integrated Chinese and Western Medicine, Jiashan Hospital affiliated of Jiaxing University, The First People's Hospital of Jiashan, Jiaxing, Zhejiang, China.

^# Contributed equally.

Abstract

Background: Epidemiologic and observational data have found a risk association between thyroid dysfunction and cutaneous malignant melanoma (CMM), however, the cause and direction of these effects are yet unknown. By using a bidirectional two-sample Mendelian randomization (MR) methodology, we hoped to further investigate the causal link between thyroid dysfunction and CMM in this work.

Methods: A genome-wide association study (GWAS) of 9,851,867 single nucleotide polymorphisms (SNPs) in a European population was used to develop genetic tools for thyroid dysfunction. Hypothyroidism was linked to 22,687 cases and 440,246 controls. For hyperthyroidism, there were 3545 cases and 459,388 controls. A total of 3751 cases and 372016 controls were included in the genetic data for CMM from UK Biobank (http://www.nealelab.is/uk-biobank) (the Dataset: ieu - b - 4969). Among them, inverse variance weighting (IVW) is the main MR Analysis method for causality assessment. MR-Egger method, MR Pleiotropic residual and outlier test (MR-PRESSO), and simple and weighted median (VM) were used to supplement the IVW method. Sensitivity analyses, mainly Cochran's Q test, leave-one-out analysis, and MR Egger intercept test were performed to assess the robustness of the outcomes.

Results: The two-sample MR Analysis results revealed a negative correlation between genetically predicted hypothyroidism and the probability of CMM (OR=0.987, 95%CI =0.075-0.999, p=0.041). The supplemental MR Analysis did not reveal any statistically significant differences, although the direction of the effect sizes for the other approaches was consistent with the IVW effect sizes. The results of the causal analysis were relatively robust, according to a sensitivity analysis. The risk of CMM was unaffected by hyperthyroidism (p>0.05). No correlation between CMM and thyroid dysfunction was seen in the reverse MR analysis.

Conclusion: Although the magnitude of the causal association is weak and further investigation of the mechanism of this putative causal relationship is required, our findings imply that hypothyroidism may be a protective factor for CMM.

Keywords: Mendelian randomization study; cutaneous malignant melanoma (CMM); hyperthyroidism; hypothyroidism; thyroid dysfunction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Genome-Wide Association Study
Humans
Hyperthyroidism*
Hypothyroidism* / complications
Hypothyroidism* / epidemiology
Hypothyroidism* / genetics
Melanoma* / epidemiology
Melanoma* / genetics
Mendelian Randomization Analysis
Skin Neoplasms*

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the Chinese Medicine Research Program of Zhejiang Province (No.2023ZR054).