Evidence map›Paper›PMID 42518596›Full record

ArticleFrontiers in genetics2026

Modifiable risk factors and skin cancers: a multi-omics Mendelian randomization study from causal inference to drug target discovery.

Zhen Qin, Wuda Huoshen, Xueqing Li, Shiyu Li, Chen Sun, Sha Yi

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Article in Frontiers in genetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

6 authors.

Zhen QinDepartment of Rheumatology and Immunology, The Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan, China.
Wuda HuoshenSchool of Stomatology, Southwest Medical University, Luzhou, Sichuan, China.
Xueqing LiSchool of Stomatology, Southwest Medical University, Luzhou, Sichuan, China.
Shiyu LiSchool of Stomatology, Southwest Medical University, Luzhou, Sichuan, China.
Chen SunDepartment of Periodontics and Oral Mucosal Diseases, The Affiliated Stomatology Hospital, Southwest Medical University, Luzhou, Sichuan, China.
Sha YiDepartment of Dermatology, Chengdu Integrated TCM & Western Medicine Hospital, Chengdu, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Introduction: Recent studies have linked modifiable risk factors (RFs) to melanoma, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). This study aimed to investigate the causal relationships between 11 modifiable RFs and these skin cancers and to identify novel therapeutic targets using multi-omics approaches. Methods: Exposure data were obtained from genome-wide association studies (GWAS). Mendelian randomization (MR) analyses were performed using the inverse variance weighted (IVW) method as the primary approach, and results from discovery and replication cohorts were combined by meta-analysis. Functional Mapping and Annotation (FUMA) and summary-data-based MR (SMR) were used to prioritize therapeutic targets. Drug prediction, phenome-wide association studies (PheWAS), and single-cell analyses were conducted to evaluate target druggability and biological relevance. Results: Actinic keratosis (AK) was associated with an increased risk of melanoma (OR = 1.24, 95% CI 1.07-1.43, P < 0.01), whereas alcohol consumption was negatively associated with SCC risk (OR = 0.77, 95% CI 0.62-0.95, P = 0.02). No causal relationships were observed between the investigated RFs and BCC. One potential therapeutic target for melanoma (EDEM2, PSMR = 0.03) and five candidate therapeutic targets for SCC (MAPK3, PSMR = 5.30E-04; NRBP1, PSMR = 4.32E-04; ANKK1, PSMR = 1.89E-06; IL27, PSMR = 3.04E-03; ADH5, PSMR = 0.02) were identified. Drug prediction, PheWAS, and single-cell analyses further supported the therapeutic potential of these genes. Discussion: AK appears to increase the risk of melanoma, whereas alcohol consumption may be protective against SCC. EDEM2 may represent a potential therapeutic target for melanoma, while MAPK3, NRBP1, ANKK1, IL27, and ADH5 are promising candidate targets for SCC. Further experimental and clinical studies are warranted to validate these findings.

Indexed as

basal cell carcinomamelanomaMendelian randomizationrisk factorssquamous cell carcinoma

Identifiers

PMID42518596
PMCPMC13384438

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