Research Paper Volume 16, Issue 7 pp 6068—6097

Associations of PD-1 and PD-L1 gene polymorphisms with cancer risk: a meta-analysis based on 50 studies

Maoquan Yang1, *, , Yan Liu2, *, , Shuangshuang Zheng3, , Peizhen Geng1, , Tianhao He2, , Linan Lu2, , Yikuan Feng2, , Qiqi Jiang2, ,

  • 1 School of Clinical Medicine, Shandong Second Medical University, Weifang 261042, Shandong, China
  • 2 Department of Gastroenterology, Weifang People’s Hospital, The First Affiliated Hospital of Shandong Second Medical University, Kuiwen, Weifang 261000, Shandong, China
  • 3 Department of Health, Weifang People’s Hospital, The First Affiliated Hospital of Shandong Second Medical University, Kuiwen, Weifang 261000, Shandong, China
* Equal contribution

Received: April 3, 2023       Accepted: February 27, 2024       Published: March 27, 2024
How to Cite

Copyright: © 2024 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Programmed death-1 and its ligand-1 (PD-1/PD-L1), immune checkpoints proteins, play a crucial role in anti-tumor responses. A large number of studies have evaluated the relationships of PD-1/PD-L1 polymorphisms with risk of cancer, but evidence for the associations remains inconsistent. Therefore, we performed a meta-analysis to examine the associations between PD-1/PD-L1 single nucleotide polymorphisms (SNPs) and cancer predisposition. Results showed that PD-1.3 and PD-L1 rs17718883 were significantly correlated with overall cancer risk. PD-1.5 was prominently linked with cervical cancer (CC), non-small cell lung cancer (NSCLC), TC (thyroid cancer), brain tumor, AML (acute myelocytic leukemia) and UCC (urothelial cell carcinoma) risk, PD-1.9 with breast cancer (BC), AML, esophageal cancer (EC) and ovarian cancer (OC) risk, and PD-1.3 with colorectal cancer (CRC) and BCC (basal cell carcinoma) risk. PD-1.1 polymorphism slightly elevated BC and OC susceptibility, whereas the rs4143815 variant notably decreased the risk of gastric cancer (GC), hepatocellular carcinoma (HCC) and OC, but increased the risk of BC. PD-1.6 was closely linked with AML risk, PD-L1 rs2890658 with NSCLC, HCC and BC risk, rs17718883 with HCC and GC risk, rs10815225 with GC risk, and rs2297136 with NSCLC and HCC risk. Interestingly, the rs7421861, rs10815225, and rs10815225 markedly reduced cancer susceptibility among Asians. The rs7421861 polymrophism decreased cancer risk among Caucasians, rather than the rs10815225 elevated cancer risk. Our results supported that PD-1 and PD-L1 SNPs were dramatically correlated with cancer risk.


CI: confidence interval; GWAS: Genome-Wide Association Studies; GWAS: genome-wide association studies; SNPs: single nucleotide polymorphism; APCs: antigen-presenting cells; HR: hazardous ratio; HWE: Hardy-Weinberg equilibrium; NOS: Newcastle-Ottawa scale; OR: odds ratio; SE: standard error; SNP: single nucleotide polymorphism; PDCD1: programmed cell death 1; PD-L1: programmed death-1 and its ligand-1; BC: breast cancer; NSCLC: non-small cell lung cancer; HCC: hepatocellular carcinoma; GC: gastric cancer; CRC: colorectal cancer; HNSCC: head and neck squamous cell carcinomas; TH: thyroid cancer; EC: esophageal cancer; OC: ovarian cancer; CC: cervical cancer; RCC: renal cell carcinoma; BCC: basal cell carcinoma; AML: acute myelocytic leukemia; UCC: urothelial cell carcinoma.