Association between PD-1 and PD-L1 Polymorphisms and the Risk of Cancer: A Meta-Analysis of Case-Control Studies

Abstract

A number of case-control studies regarding the association of the polymorphisms in the programmed cell death 1 (PD-1) and programmed cell death ligand 1 (PD-L1) genes with the risk of cancer have yielded inconsistent findings. Therefore, we have conducted a comprehensive, updated meta-analysis study to identify the impact of <i>PD-1</i> and <i>PD-L1</i> polymorphisms on overall cancer susceptibility. The findings revealed that <i>PD-1</i> rs2227981 and rs11568821 polymorphisms significantly decreased the overall cancer risk (Odds Ratio (OR) = 0.82, 95% CI = 0.68-0.99, <i>p</i> = 0.04, TT vs. CT+CC; OR = 0.79, 95% CI = 0.67-0.94, <i>p</i> = 0.006, AG vs. GG, and OR = 0.82, 95% CI = 0.70-0.96, <i>p</i> = 0.020, AG+AA vs. GG, respectively), while <i>PD-1</i> rs7421861 polymorphism significantly increased the risk of developing cancer (OR = 1.16, 95% CI = 1.02-1.33, <i>p</i> = 0.03, CT vs. TT). The <i>PD-L1</i> rs4143815 variant significantly decreased the risk of cancer in homozygous (OR = 0.62, 95% CI = 0.41-0.94, <i>p</i> = 0.02), dominant (OR = 0.70, 95% CI = 0.50-0.97, <i>p</i> = 0.03), recessive (OR = 0.76, 95% CI = 0.60-0.96, <i>p</i> = 0.02), and allele (OR = 0.78, 95% CI = 0.63-0.96, <i>p</i> = 0.02) genetic models. No significant association between rs2227982, rs36084323, rs10204525, and rs2890658 polymorphisms and overall cancer risk has been found. In conclusions, the results of this meta-analysis have revealed an association between <i>PD-1</i> rs2227981, rs11568821, rs7421861, as well as <i>PD-L1</i> rs4143815 polymorphisms and overall cancer susceptibility.