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Evaluating the causality between skin tanning, radiated disorders, and basal cell carcinoma: a multivariable Mendelian randomization analysis

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Abstract

The causality of ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue with basal cell carcinoma (BCC) remains unclear. Our objective was to investigate whether ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue have a relation with the occurrence and development of BCCs. In this work, independent genetic variants strongly associated (P < 5e−08) with ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue were selected as instrumental variables from corresponding genome-wide association studies (GWASs). Summary-level data for BCC was obtained from the European Bioinformatics Institute (EBI). Two-sample univariable and multivariable Mendelian randomization (MR) were performed. Sensitivity analyses were preformed via MR-Egger regression, heterogeneity test, pleiotropy test, and leave-one-out sensitivity test. We observed positive causal effect both for ease of skin tanning [odds ratio (OR) = 2.102, 95% confidence interval (CI) = 1.915–2.306, P = 2.71e−55] and radiation-related disorders of the skin and subcutaneous (OR = 1.603, 95% CI = 1.483–1.734, P = 3.41e−32) on occurrence of BCCs based on univariable MR analyses. In the multivariable mendelian randomization (MVMR) analysis of BCC risk, we also observed a direct causal effect of ease of skin tanning (ORMVMR = 1.623, 95% CI = 1.445–1.824, PMVMR =3.41e−16) and radiation-related disorders of the skin and subcutaneous (ORMVMR = 1.208, 95% CI = 1.107–1.319, PMVMR = 2.46e−05) on BCCs. The findings suggest that the high risk of BCCs can be attributed to ease of skin tanning and radiation-related disorders of the skin and subcutaneous tissue.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request or the website https://gwas.mrcieu.ac.uk/.

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Acknowledgements

The authors thank all patients who participated in the GWAS studies.

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Authors and Affiliations

  1. Department of Dermatology, the Third Xiangya Hospital, Central South University, No.138 Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, China

    Chunli Chen & Jianyun Lu

  2. Reproductive Medical Center, Hainan Women and Children’s Medical Center, Haikou, 570208, Hainan, China

    Bangbei Wan & Weiying Lu

Authors
  1. Chunli Chen
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  2. Bangbei Wan
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  3. Weiying Lu
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  4. Jianyun Lu
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Contributions

All authors contributed to the study conception and design. Chunli Chen and Bangbei Wan preformed data collection, data analysis, and manuscript drafting. Weiying Lu and Jianyun Lu were responsible for manuscript drafting and modifying. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Jianyun Lu.

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Our study did not require an ethical board approval because it did not contain human or animal trails.

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Responsible Editor: Lotfi Aleya

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Supplementary information

ESM 1

Supplementary Figure 1 (A) Radial plots of the MR−Egger test analyzed the outlier SNPs of ease of skin tanning. (B) Radial plots of the MR−Egger test analyzed the outlier SNPs of radiation-related disorders of the skin and subcutaneous tissue. (C) MR density plots to visualize the overall heterogeneity of MR estimates for the effect of ease of skin tanning on BCC. (D) MR density plots to visualize the overall heterogeneity of MR estimates for the effect of radiation-related disorders of the skin and subcutaneous tissue on BCC. MR, Mendelian randomization; SNP, single-nucleotide polymorphism; BCC, basal cell carcinoma (PDF 4 kb)

ESM 2

Supplementary Figure 2 Leave-one-out plots of radiation-related disorders of the skin and subcutaneous tissue with the risk of BCC. Leave-one-out analysis for IVW MR of Radiation-related disorders of the skin and subcutaneous tissue on BCC in summary-level analyses. SNP, single-nucleotide polymorphism; MR, Mendelian randomization; BCC, basal cell carcinoma (PDF 10 kb)

ESM 3

Supplementary Figure 3 Leave-one-out plots of ease of skin tanning with the risk of BCC. Leave-one-out analysis for IVW MR of ease of skin tanning on BCC in summary-level analyses. SNP, single-nucleotide polymorphism; MR, Mendelian randomization; BCC, basal cell carcinoma (PDF 594 kb)

ESM 4

(DOCX 59 kb)

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Chen, C., Wan, B., Lu, W. et al. Evaluating the causality between skin tanning, radiated disorders, and basal cell carcinoma: a multivariable Mendelian randomization analysis. Environ Sci Pollut Res 30, 71001–71006 (2023). https://doi.org/10.1007/s11356-023-27420-4

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  • DOI: https://doi.org/10.1007/s11356-023-27420-4

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