Germline PDCDL1 Gene Variants Are Associated with Increased Primary Melanoma Thickness

<b>Background</b>: The incidence of malignant melanoma (MM) continues to increase annually, and tumour invasiveness is a main prognostic factor. Single-nucleotide polymorphisms (SNPs) have become key tools in the study of cancer genetics, influencing susceptibility and prognosis. <b>Methods</b>: In the present study, we analysed the relationship between five SNPs on the <i>PDCDL1</i> gene (rs822336, rs822337, rs822338, rs229736, rs4143815) with prognosis as well as primary tumour invasiveness characteristics in 377 whole blood samples from MM individuals. <b>Results</b>: Patients who presented the rs822336 CG or GG genotypes (OR = 3.01, 95% CI = 1.53-5.92; <i>p</i> = 0.0017), TA or TT in rs822337 (OR = 2.45, 95% CI = 1.22-4.93; <i>p</i> = 0.0098), and CT or CC of rs822338 (OR = 2.23, 95% CI = 1.05-4.73; <i>p</i> = 0.028) were at an increased risk of developing invasive melanomas. Cases with the AG or GG genotype in rs2297136 presented a lower risk (OR = 0.29, 95% CI = 0.11-0.75; <i>p</i> = 0.0038) of invasive MM. The genetic analysis at the haplotype level resulted in similar findings (OR: 2.95, 95% CI: 1.08-8.10), <i>p</i> = 0.036). Furthermore, patients carrying the homozygous AA genotype in rs2297136 had thicker tumours than those harbouring the AG or GG (1.4 mm vs. 1.0 and 0.8 mm; <i>p</i> = 0.030). No significant association was found between the studied SNPs and melanoma-specific survival (MSS) nor progression-free survival (PFS). <b>Conclusions</b>: Current results suggest that SNPs rs822336, rs822337, rs822338, and rs2297136 genotypes in the <i>PDCDL1</i> gene are associated with the risk of tumour invasiveness and tumour thickness in MM. Further studies on SNPs considering genetic and epigenetic factors are needed for a better understanding of malignant melanoma susceptibility and its prognosis.