Assessing MC1R Variants in Lentigo Maligna Melanoma Within the Utah Population.

Abstract

Lentigo maligna (LM) and lentigo maligna melanoma (LMM) arise from chronically sun-damaged skin. LM/LMM incidence continues to rise, particularly in Utah, where melanoma rates are twice the national average. The melanocortin-1 receptor (MC1R) has been studied in melanocyte pigmentation and DNA repair but have yet to be thoroughly investigated in LM/LMM. We investigated allele and genotype frequencies of germline MC1R variants among 175 Utah patients diagnosed with LM/LMM and 402 Utah reference individuals. The comparative analysis demonstrated increased frequency of the D294H allele (0.046; p = 0.0042) and decreased frequency of the V60L allele (0.074; p = 0.034) in LM/LMM patients. The LM/LMM group demonstrated a higher OR compared to the Utah reference group associated with R151C homozygosity compared to heterozygous R151C (OR = 5.6, 95%CI = 0.98-32, p = 0.052) and R151C homozygosity compared to wildtype (OR = 5.7, 95%CI = 1.1-30, p = 0.042). D294H heterozygosity was strongly associated with LM/LMM (OR = 3.8, 95%CI = 1.3-11, p = 0.014). Conversely, V60L heterozygosity was less strongly associated with LM/LMM (OR = 0.52, 95%CI = 0.26-1.1, p = 0.072). Stratified analyses show no significant differences in age or gender across the key MC1R variants studied. These data highlight significant differences in MC1R allele frequencies in patients with LM/LMM, demonstrating that D294H is associated with increased LM/LMM risk, while the V60L variant is inversely associated with risk. This study provides the first comprehensive analysis of specific high-risk MC1R variants in LM/LMM patients in Utah.