Can a UV-Resistance Gene Predict Skin Cancer Risk?

The UV radiation resistance-associated (UVRAG) tumor suppressor gene coordinates DNA repair and might predict skin cancer risk, according to research published in the journal Molecular Cell.

“Our study suggests that the UV-resistant gene may serve as a biomarker for skin cancer prevention,” reported coauthor Chengyu Liang, MD, PhD, of the Keck School of Medicine at the University of Southern California, Los Angeles, in a news release.

UV-associated DNA damage is an important risk factor for melanoma, the authors noted. UVRAG activates the CRL4^DDB2 ubiquitin ligase complex, coordinating repair of UV-associated DNA damage, the researchers found.

The team analyzed data for 340 melanoma patients from The Cancer Genome Atlas. The study did not include a control group of noncancer patients, so the findings do not definitively link UVRAG variants or expression with cancer risk, the authors cautioned. However, UVRAG expression levels were associated with melanoma metastasis and patient survival, they reported.

The team also confirmed a relationship between UVRAG and repair of UV-induced DNA damage in subsequent experiments with melanoma cell lines and a Drosophila fly model. In the experiments, repair of UV exposure-induced DNA damage was more complete (50% of cells after 24 hours) for cells harboring wild-type UVRAG than mutant variants (20%), they reported.

“UVRAG is strictly required for global genomic nucleotide excision repair,” the coauthors concluded. “UVRAG expression inversely correlates with UV-like mutagenesis in melanoma.”

The gene has no known enzymatic activity, but supports or coordinates DNA repair. Without that coordination, “the whole structure collapses,” noted Dr. Liang.

“This means when people sunbathe or go tanning, those who have the normal UV-resistant gene can repair most UV-induced DNA burns in a timely manner, whereas those with defective UV-resistant gene will have more damage left unrepaired,” Dr. Liang noted. “After daily accumulation, if they sunbathe or go tanning often, these people will have increased risk for developing skin cancers such as melanoma.”

The findings might eventually lead to development of new drugs, the authors suggested.