# Skin cancer risk in hereditary mixed cancer syndromes

## TL;DR

This paper reviews how certain inherited genetic conditions increase the risk of skin cancers and suggests tailored screening and prevention strategies.

## Contribution

The paper highlights underrecognized skin cancer risks in hereditary cancer syndromes and recommends dermatologic evaluations for affected individuals.

## Key findings

- Li-Fraumeni, Lynch, and HBOC syndromes are linked to increased skin cancer risks.
- Pathogenic ATM and CHEK2 variants may predispose individuals to skin cancers.
- Dermatologic evaluation and UV protection strategies are recommended for early detection.

## Abstract

Hereditary cancer syndromes are genetic conditions that increase an individual’s risk for multiple cancer types, often due to mutations that affect critical cellular processes such as DNA repair and cell cycle regulation. Skin cancers, including malignant melanoma (MM), basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and related precancerous lesions may be underrecognized in some hereditary cancer syndromes, as suggested by underlying biological mechanisms and their underreporting in studies. In this narrative review, we examine the skin cancer risks associated with the most prevalent hereditary cancer syndromes, including Li-Fraumeni syndrome (LFS), Lynch syndrome (LS), hereditary breast and ovarian cancer syndrome (HBOC), ATM-associated hereditary cancer syndrome, CHEK2-associated hereditary cancer syndrome, BRIP1-associated cancer predisposition, and hereditary leiomyomatosis and renal cell carcinoma (HLRCC). This review consolidates existing evidence and suggests that mixed cancer syndromes, especially LFS, LS, and HBOC but also pathogenic ATM and CHEK2 variants may predispose individuals to skin cancers, warranting tailored screening and preventive measures. On the basis of emerging evidence, we recommend dermatologic evaluation and individualized UV protection strategies for patients with reviewed hereditary cancer syndromes to reduce skin cancer risk and enhance early detection.