Genetic variants of and in myeloid cell-related pathway genes independently predict cutaneous melanoma-specific survival.

UNLABELLED

Both and evidence has supported a key role of myeloid cells in immune suppression in melanoma and in promoting melanocytic metastases. Some single-nucleotide polymorphisms (SNPs) have been shown to predict cutaneous melanoma-specific survival (CMSS), but the association between genetic variation in myeloid cell-related genes and cutaneous melanoma (CM) patient survival remains unknown.

METHODS

we investigated associations between SNPs in myeloid cell-related pathway genes and CMSS in a discovery dataset of 850 CM patients and replicated the findings in another dataset of 409 CM patients.

RESULTS

we identified two SNPs ( rs10151787 A>G and rs2069018 T>C) as independent prognostic factors for CMSS, with adjusted allelic hazards ratios of 1.56 (95% confidence interval =1.19-2.05, =0.001) and 1.66 (1.22-2.26, =0.001), respectively; so were their combined unfavorable alleles in a dose-response manner in both discovery and replication datasets ( <0.001 and 0.002, respectively). Additional functional analysis revealed that both rs10151787 G and rs2069018 C alleles were associated with elevated mRNA expression levels in normal tissues.

CONCLUSIONS

Our findings suggest that rs10151787 A>G and rs2069018 T>C are independent prognostic biomarkers for CMSS.