A recent study has highlighted significant associations between specific single nucleotide variants (SNVs) in the PD-1 and PD-L1 genes and the risk of metastatic melanoma (MM). Researchers conducted the study at IRCCS Ospedale Policlinico San Martino in Genova, Italy, and included 125 patients with advanced melanoma treated with anti-PD-1 agents and 84 healthy controls.

The results revealed that the PD1.5 C>T (rs2227981) variant was linked with a reduced risk of MM. The T/T genotype was associated with a 44% lower risk compared to the C/C genotype (RR = 0.56, 95% CI: 0.37–0.87, P = 0.011). A protective effect was observed with the combined C/T and T/T genotypes (RR = 0.73, 95% CI: 0.59–0.90, P = 0.003). Allergic modeling confirmed the associations (RR = 0.78, 95% CI: 0.65–0.91, P = 0.003).

For the PD1.7 T>C (rs7421861) variant, the data indicated an increased risk for MM, with the C/C genotype presenting a significantly higher risk (RR = 1.65, 95% CI: 1.32–2.05, P < 0.001) versus the T/T genotype. Recessive modeling showed an elevated risk with the C/C genotype (RR =1.58, 95% CI: 0.95–2.64, P = 0.077), a trend confirmed with allelic modeling (RR = 1.23, 95% CI: 1.06–1.43, P = 0.007). No significant associations between MM occurrence and other studied PD-1 and PD-L1 SNVs were reported.

"Our results extend our previous findings on the diverse roles of PD-1 SNVs in the context of MM," the study team concluded. "However, further studies will be needed in larger and different populations to evaluate the relationship between PD-1 and PDL-1 SNVs and MM risk."

The authors also noted the limitations. 

"A critical limitation of our study is the exclusive focus on MM cases, which may slightly affect the generalizability of our findings," they added. "Consequently, the associations we have described here are specific to MM patients and probably could not be extended to the general melanoma susceptibility, especially when compared to the representative sample of the general population (healthy donors)."

Source: Boutros A, et al. Archives of Dermatological Research. 2024. Doi:10.1007/s00403-024-03034-9