Inherited genetic markers in immune response pathways associated with melanoma survival.
Inherited genetic markers could help determine a melanoma cancer patient’s length of survival, a recent study found.
Melanoma accounts for just 4% of all skin cancers, but is responsible for 80% of all skin cancer deaths.
Despite recent treatment improvements, risk assessments consist of clinical and pathological tests that are unable to tailor a prognosis to the individual patient.
Since melanoma has the ability to trick the immune system and escape surveillance, researchers concentrated on inherited genetic markers found in the body’s immune response pathways in a study published in Clinical Cancer Research.
"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," said senior study author Tomas Kirchhoff, PhD.
Researchers looked at nearly 400 expression quantitative trait loci (eQTLs), which are gene variants that take part in regulating the immune system, to find inherited genetic markers. The genetic markers are located in the human genome and although they don’t directly produce proteins, they do affect gene activation.
Researchers also looked at the database from a UK-based project called Multiple Tissue Human Expression Resource (MuTHER), which collected eQTL data from numerous healthy twins. The nearby immune genes in the twin population were tested in samples collected from 1221 patients.
The results of the study showed that 2 gene variants showed a connection with melanoma survival. When both gene variants were tested together in the human samples, they had the strongest predictions of melanoma survival.
"This joint test showed that the two markers do not fully correlate with established pathological predictors, suggesting their independent clinical relevance," Kirchhoff said.
Researchers also identified 2 specific combinations of genotypes that appeared in approximately 60% of the population. These were associated with a shorter survival rate in melanoma patients.
The 2 unfavorable genotypes for survival are found on chromosome 1, which have a tight cluster of 5 interleukin genes that help regulate the immune response. These genotypes were associated with the decreased activation of 2 interleukin genes (IL10 and IL19).
"We strongly suspect that the genetic variants we identified impact balanced activation of these interleukins, which could play a major role in the progression of melanoma towards more aggressive, metastatic disease," Kirchhoff said. "In turn, this imbalanced immunity determines, or modulates, melanoma survival."
In the future, researchers hope to replicate their observations in a bigger patient group. They will look to see if they can target the 2 biomarkers in patients who are in the early stages of melanoma and have a higher risk for unfavorable outcomes.