Prognosis for patients with cutaneous melanoma may be predicted by an inherited genetic marker that provides a personalized tool to gauge a person’s survival and determine if closer monitoring is needed in the years following surgery. These findings, from a novel analysis of immunoregulatory pathways, were published in Clinical Cancer Research (doi:10.1158/1078-0432.CCR-15-2066).
Melanoma accounts for almost 10 000 of the more than 13 000 skin cancer deaths each year, according to the American Cancer Society. A critical question is determining which patients with melanoma are at greatest risk; therefore, more specific and sensitive tests for tailoring prognosis to individual patients are needed.
This study provides strong evidence supporting the use of genetic markers to improve clinicians’ ability to determine a prognosis for patients with melanoma. This complements existing tools used in clinical practice.
“There are gene variants that we inherit from our parents that don’t increase our susceptibility to developing melanoma, but once the diseases strikes, they can alter outcome,” said Tomas Kirchhoff, PhD, assistant professor in the Department of Population Health at NYU Langone and a member of the Perlmutter Cancer Center in New York, New York, and senior author of the study.
Melanoma progresses by tricking the immune system and escaping its surveillance. So, the research team focused on inherited genetic markers found in the pathways of the body’s immune response.
“We hypothesized that if someone inherits a certain genetic variant that suppresses immunity, there is a much higher chance that once melanoma strikes, it will progress faster,” Kirchhoff said.
The researchers surveyed nearly 400 gene variants, called expression quantitative trait loci (eQTLs), that are involved in immune regulation in humans. These inherited genetic markers affect the activation of genes located nearby, though they themselves are located in areas of noncoding DNA.
The researchers examined eQTL data from a large number of normal twins from a healthy population to find genetic variants most significantly correlated with the activation of nearby immune genes in the normal twin population. These variants were tested in samples collected from 1221 patients in the NYU Langone Interdisciplinary Melanoma Cooperative Group.
Melanoma survival had a significant association with 2 of these gene variants, and was most strongly predicted when both gene variants were tested together in the human samples.
“This joint test showed that the 2 markers do not fully correlate with established pathological predictors, suggesting their independent clinical relevance,” Kirchhoff said.
A specific combination of the 2 markers, or genotype, was identified in approximately 60% of the human population and found to be associated with less favorable, shorter survival in those patients with melanoma. Average survival was 5 years longer for the remaining 40% of patients with the alternative genotypes.
This study was supported by grants from the National Cancer Institute and the Cancer Center Support Grant.