Childhood sunburn and risk of melanoma and non-melanoma skin cancer: a Mendelian randomization study

Yajia Li; Jianhuang Wu; Ziqin Cao

doi:10.1007/s11356-023-30535-3

Childhood sunburn and risk of melanoma and non-melanoma skin cancer: a Mendelian randomization study

Environ Sci Pollut Res Int. 2023 Dec;30(58):122011-122023. doi: 10.1007/s11356-023-30535-3. Epub 2023 Nov 14.

Authors

Yajia Li^{1

2}, Jianhuang Wu^{2

3}, Ziqin Cao^{4

5}

Affiliations

¹ Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
² National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
³ Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China.
⁴ National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China. xyeyyziqincao@csu.edu.cn.
⁵ Department of Spine Surgery and Orthopaedics, Xiangya Hospital, Central South University, Changsha, China. xyeyyziqincao@csu.edu.cn.

Abstract

Previous evidence has suggested that childhood sunburn could be a risk factor for cutaneous malignant melanoma (MM) and non-melanoma skin cancer (NMSC). However, existing observational studies could not reveal the causal associations genetically. This study aimed to investigate whether there was a genetic causal relationship between childhood sunburn and skin cancers. Univariable Mendelian randomization (MR) and Causal Analysis Using Summary Effect analysis was carried out for causal estimates and evaluation for the horizontal pleiotropy. Multivariable MR and the mediation effects analysis were used to test whether the causal associations were mediated by potential confounders. A suggestively significant causal association between childhood sunburn and MM was indicated (OR = 4.74; 95% CI: 1.31-17.19; p = 1.79E-02). Genetically predicted childhood sunburn was significantly associated with increased risk of overall melanoma in situ (MIS) (OR = 4.02; 95% CI: 2.00-8.08; p = 9.40E-05), MIS of face (OR = 18.28; 95% CI: 5.28-63.35; p = 4.59E-06), and MIS of trunk (OR = 7.05; 95% CI: 2.06-24.13; p = 1.88E-03). Similar trends were found for childhood sunburn and NMSC (OR = 8.16; 95% CI: 6.07-10.99; p = 1.53E-20), including both basal cell carcinoma (BCC) (OR = 3.76; 95% CI:2.96-4.77; p = 2.19E-08) and squamous cell carcinoma (SCC) (OR = 7.44; 95% CI: 5.09-10.87; p = 2.19E-08). After adjustment for hair and skin color, facial ageing, vitamin D levels, body mass index, alcohol consumption, and smoking status, childhood sunburn showed an independent association with MIS, MIS of face, MIS of trunk, as well as NMSC, including both BCC and SCC. Mediation analysis showed no significant mediation effect. This study demonstrated a causal relationship between childhood sunburn and the risk of both MM and NMSC, which suggested that enhanced screening and prevention for childhood sunburn could contribute to the early detection and decreased risk of MM and NMSC.

Keywords: Childhood; Clinical pathology; Genetic background; Genome-wide association study; Mendelian randomization; Skin cancer; Sunburn.

MeSH terms

Carcinoma, Basal Cell* / complications
Carcinoma, Squamous Cell*
Child
Humans
Melanoma* / complications
Melanoma* / epidemiology
Mendelian Randomization Analysis
Risk Factors
Skin Neoplasms* / epidemiology
Sunburn* / complications
Sunburn* / epidemiology