# Identifying clinical and genetic factors for risk of multiple skin cancers in organ transplant recipients

> **NIH VA IK2** · VETERANS HEALTH ADMINISTRATION · 2024 · —

## Abstract

PROJECT SUMMARY
 Since 1999, 9% of all Veterans nationwide have been diagnosed with skin cancer. Skin
cancer is the most common malignancy in the United States with more than 5 million individual
cancers costing an estimated $8.1 billion to treat annually. Veterans have skin cancer rates as
much as four times higher than the civilian population and report greater sun exposures, more
frequent sunburns, and lower use of sun protection. Skin cancer incidence is therefore
anticipated to continue increasing among Veterans. Unlike other cancer types, patients will often
develop multiple skin cancers, and half of skin cancer-related deaths occur among those with 10
or more skin cancers. Skin cancer risk is heterogeneous, but little progress has been made in
determining which patient will develop numerous skin cancers.
 Patients with 10 or more skin cancers have a 25% risk of metastasis. Studying
populations with a high prevalence of multiple skin cancers can provide clues to mechanisms of
multiple skin cancer development. Organ transplant recipients (OTR) have up to 100-fold
greater rates of skin cancer than non-OTR. This increase is believed to be due to both
immunosuppression and decreased DNA repair caused by immunosuppressants. Exposure to
specific immunosuppressants is associated with varying risks of skin cancer, although how their
metabolism affects the number of skin cancers is unknown. Further, it is unclear if other factors
present at the time of transplant can identify individuals at high risk for multiple skin cancers
who would benefit from aggressive primary prevention. This study will use VINCI and MVP data
to address the critical knowledge gap of how to identify Veterans at risk of developing 10 or
more skin cancers a priori to reduce their skin cancer morbidity and mortality.
 The overall goal of this CDA-2 is to advance the personalized management of skin
cancer in organ transplant recipients and provide clues to mechanisms of disease in the broader
Veteran population. Our long-term goal is to deploy precision medicine management strategies
to reduce skin cancer incidence, morbidity, and mortality among both Veterans with organ
transplants and Veterans overall. In Aim 1, we will identify patterns of clinical factors present at
the time of transplant that are associated with skin cancer development. In Aim 2, we will
investigate how variation in metabolism of immunosuppressant medications impacts the number
of skin cancers a patient will develop. In Aim 3, we will examine the role of rare genetic variants
in developing 10 or more skin cancers.
 The Tennessee Valley Healthcare System Nashville VA and Vanderbilt are an ideal
environment to support Dr. Wheless for this proposal and his transition to an independent
physician scientist. Both hospitals are high-volume transplant centers and house strong
bioinformatics infrastructure and expertise. The Department of Dermatology strongly supports
Dr. Wheless’s career development. His mentors, Dr...

## Key facts

- **NIH application ID:** 10811623
- **Project number:** 5IK2CX002452-02
- **Recipient organization:** VETERANS HEALTH ADMINISTRATION
- **Principal Investigator:** LEE E WHELESS
- **Activity code:** IK2 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10811623

## Citation

> US National Institutes of Health, RePORTER application 10811623, Identifying clinical and genetic factors for risk of multiple skin cancers in organ transplant recipients (5IK2CX002452-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10811623. Licensed CC0.

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