Actinic keratosis increases melanoma risk while alcohol consumption is associated with lower squamous cell carcinoma riskActinic Keratosis Linked to Higher Risk of Melanoma

Frontiers in Medicine Published July 8, 2026 DOI ↗ Editorial oversight: Dr. Julia Lee, PhD · Oncology, Genomics & Drug Development

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Key Takeaway

Note that actinic keratosis increases melanoma risk while alcohol consumption is associated with lower squamous cell carcinoma risk.

This meta-analysis utilizes Mendelian randomization to investigate the causal relationships between 11 modifiable risk factors, including actinic keratosis and alcohol consumption, and various skin cancers. The analysis focused on identifying both risk associations and potential therapeutic targets for melanoma and squamous cell carcinoma (SCC).

The findings indicate that actinic keratosis is associated with an increased risk of melanoma (OR = 1.24; 95% CI 1.07-1.43, P < 0.01). Conversely, alcohol consumption was associated with a decreased risk of squamous cell carcinoma (OR = 0.77; 95% CI 0.62-0.95, P = 0.02). No causal relationships were observed between modifiable risk factors and basal cell carcinoma.

Regarding therapeutic targets identified via summary Mendelian randomization, EDEM2 was identified as a potential target for melanoma (PSMR = 0.03). For squamous cell carcinoma, several candidate targets were identified including MAPK3, NRBP1, ANKK1, IL27, and ADH5 (PSMR values ranging from 5.30E-04 to 0.02). The authors note that these findings require further experimental and clinical studies for validation.

How this fits prior evidence

This meta-analysis addresses gaps in understanding the causal links between modifiable risk factors and skin cancers. It provides specific data on actinic keratosis as a melanoma risk factor and identifies potential therapeutic targets like EDEM2 and MAPK3. These findings complement existing knowledge on melanoma management, such as the use of IO102-IO103 plus pembrolizumab for advanced melanoma.

Researchers analyzed genetic data to look at how different lifestyle factors and conditions affect the risk of developing skin cancers, including melanoma, basal cell carcinoma, and squamous cell carcinoma. This type of study uses a method called Mendelian randomization to help determine if there is a direct link between these factors and cancer.

The analysis found that actinic keratosis was associated with an increased risk of melanoma. Interestingly, the data showed a lower risk of squamous cell carcinoma for those who consumed alcohol. No clear links were found between the studied risk factors and basal cell carcinoma.

While the study identified several potential targets for future treatments, such as EDEM2 for melanoma and others like MAPK3 or IL27 for squamous cell carcinoma, these are not yet approved drugs or proven treatments. Because this was a large-scale data analysis rather than a clinical trial, more research is needed to confirm these findings before they can change how doctors treat patients.

What this means for you:

Actinic keratosis is linked to higher melanoma risk, and several new targets for skin cancer treatment were identified.

Common questions

What is the link between actinic keratosis and melanoma?

The study found that actinic keratosis was associated with an increased risk of melanoma. Specifically, the data showed a calculated odds ratio of 1.24 for those with the condition. However, because this was a large-scale data analysis, more clinical studies are needed to confirm these results.

Were any new treatments found for skin cancer?

The study identified several potential targets for future research, such as EDEM2 for melanoma and MAPK3, NRBP1, ANKK1, IL27, and ADH5 for squamous cell carcinoma. These are not currently approved drugs or established treatments; they are only candidates for future medical development.

Did the study find a link between alcohol and skin cancer?

The analysis showed that alcohol consumption was associated with a decreased risk of squamous cell carcinoma. This finding is based on genetic data models rather than direct clinical observation, so it should be discussed with a doctor for personal health context.

Study Details

Study typeMeta analysis

EvidenceLevel 1

PublishedJul 2026

View Original Abstract ↓

IntroductionRecent 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.MethodsExposure 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.ResultsActinic 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.DiscussionAK 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.

Actinic keratosis increases melanoma risk while alcohol consumption is associated with lower squamous cell carcinoma riskActinic Keratosis Linked to Higher Risk of Melanoma

How this fits prior evidence

Common questions

Study Details

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Actinic keratosis increases melanoma risk while alcohol consumption is associated with lower squamous cell carcinoma riskActinic Keratosis Linked to Higher Risk of Melanoma

How this fits prior evidence

Common questions

More on Melanoma

Study Details

TLR4 Asp299Gly polymorphism associated with increased infection susceptibility (OR 2.05) and mortality (HR 1.78)

Genetic variations linked to higher risk of severe infections

Clinical research that matters. Delivered to your inbox.

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