Causal association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma: a two-sample Mendelian randomization study

Beichen Cai; Qian Lin; Ruonan Ke; Xiuying Shan; Jiaqi Yu; Xuejun Ni; Xinjian Lin; Biao Wang

doi:10.3389/fonc.2023.1154107

Causal association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma: a two-sample Mendelian randomization study

Front Oncol. 2023 Aug 17:13:1154107. doi: 10.3389/fonc.2023.1154107. eCollection 2023.

Authors

Beichen Cai^{1

2

3

4}, Qian Lin^{1

3

4}, Ruonan Ke^{1

3}, Xiuying Shan^{1

3}, Jiaqi Yu^{1

3

4}, Xuejun Ni^{1

3}, Xinjian Lin^{1

3

5}, Biao Wang^{1

2

3

4}

Affiliations

¹ Department of Plastic Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.
² Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, Fujian, China.
³ Department of Plastic Surgery, National Regional Medical Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, China.
⁴ Fujian Key Laboratory of Translational Research in Cancer and Neurodegenerative Diseases, Institute for Translational Medicine, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, Fujian, China.
⁵ Key Laboratory of Gastrointestinal Cancer, Fujian Medical University, Ministry of Education, Fuzhou, Fujian, China.

Abstract

Background: Despite numerous observational studies on the association between serum 25-Hydroxyvitamin D levels and cutaneous melanoma, causal inferences remain ambiguous due to confounding and reverse causality. This study aimed to elucidate the causal relationship between serum 25-Hydroxyvitamin D levels and melanoma incidence using Mendelian randomization (MR).

Methods: A two-sample MR was conducted using genetic variants associated with serum 25-Hydroxyvitamin D levels as instrumental variables. Summary statistics for these variants were derived from genome-wide association studies, and those for melanoma risk were obtained from a comprehensive melanoma case-control study. Robustness of the results was assessed through sensitivity analyses, including the "leave-one-out" approach and tests for potential pleiotropy.

Results: The MR analysis provided substantial evidence of a positive causal relationship between serum 25-Hydroxyvitamin D levels and the incidence of cutaneous melanoma, suggesting that each unit increase in serum 25-Hydroxyvitamin D levels corresponds with an increased risk of melanoma. Tests for pleiotropy showed minimal effects, and the sensitivity analysis confirmed no disproportionate influence by any individual single nucleotide polymorphism (SNP).

Conclusion: The findings indicated a potentially causal positive association between serum 25-Hydroxyvitamin D levels and melanoma risk, challenging traditional beliefs about vitamin D's role in melanoma. This emphasizes the need for a balanced and personalized approach to vitamin D supplementation and sun exposure, particularly in high-risk populations. These results should be interpreted with caution due to potential unrecognized pleiotropy and confounding factors. Future research should focus on validating these findings in diverse populations and exploring underlying biological mechanisms.

Keywords: Mendelian randomization; causal inference; cutaneous melanoma; genetic variants; serum 25-hydroxyvitamin D; sun exposure.

Grants and funding

This work was supported by grants from Special Scientific Research Project of Fujian Provincial Finance Project (No. 2019B031); Young and Middle-aged Key Personnel Training Project of Fujian Provincial Health Commission(No. 2020GGB029); Youth Scientific Research Project of Fujian Provincial Health Commission(No. 2020QNA048); Startup Fund for Scientific Research of Fujian Medical University (No. 2019QH2030).