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Background <p>Immune checkpoint pathways regulating T cell activity are key targets in cancer therapy. Genetic variations in checkpoint molecules (CTLA-4, PD-1, PD-L1) can alter signaling pathways, affecting cancer risk and treatment response in various types of malignancies.</p> Methods <p>This study aimed to investigate associations between common polymorphisms in immune-regulating genes (<i>CTLA-4</i>, <i>PDCD1</i> and <i>CD274</i>) and susceptibility to nasopharyngeal carcinoma (NPC) in the Tunisian population. We analyzed six polymorphisms: rs231775 and rs3087243 (<i>CTLA-4</i>), rs2227981, rs2227982, and rs36084323 (<i>PDCD1</i>), and rs2890658 (<i>CD274</i>) in a case–control study which enrolled 61 Tunisian NPC patients and 150 matched healthy controls using the PCR-RFLP method.</p> Results <p>For the rs231775 SNP, our findings showed a significant association between the AA genotype and increased NPC susceptibility in the recessive model (GG + AG vs. AA) (p<sub>c</sub>=0.006, OR = 2.5, 95% CI: [1.35–4.6]). Further, the haplotype analysis showed that the rs231775 &gt; A-rs3087243 &gt; A-rs36084323 &gt; G-rs2227982 &gt; C-rs2227981 &gt; C risk haplotype was significantly more expressed in NPC patients (<i>p</i> = 0.044, OR = 1.64, 95% CI: [1.02–2.63]). The phenotype-genotype association revealed that the rs231775 &gt; AA genotype was significantly associated with clinical manifestations. We also confirmed that the rs2890658 &gt; CC genotype was significantly associated with increased risk of NPC under the recessive model (AA + CA vs. CC), <i>p</i> = 0.0001, OR = 3.2, 95% CI: [1.71 − 5.96]. In addition, the rs2890658 &gt; C variant had a 2.4-fold higher risk of NPC in comparison with the A allele (<i>p</i> = 0.0009, OR = 2.4, 95% CI: [1.42 − 4.08]).</p> Conclusion <p>Our results suggest that the <i>CTLA-4_</i>rs231775 &gt; AA and <i>CD274_</i>rs2890658 &gt; CC genotypes could be considered as predisposition factors for NPC. These findings could pave the way for future investigations into NPC pathogenesis and assessing <i>CTLA-4</i>, <i>PDCD1</i>, and <i>CD274</i> as personalized therapeutic targets.</p>

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Functional genetic variants in immune-checkpoint molecules and susceptibility to Nasopharyngeal carcinoma in a Tunisian case-control study

  • 期刊论文

  • 发表日期：

    2025年12月29日

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  • Wejden Gharbi,
  • Wicem Siala,
  • Olfa Abida,
  • Bassem Lahiani,
  • Sawsan Feki,
  • Ikram Ben Amor,
  • Jamel Daoud,
  • Hatem Masmoudi,
  • Hend Hachicha

摘要

Background

Immune checkpoint pathways regulating T cell activity are key targets in cancer therapy. Genetic variations in checkpoint molecules (CTLA-4, PD-1, PD-L1) can alter signaling pathways, affecting cancer risk and treatment response in various types of malignancies.

Methods

This study aimed to investigate associations between common polymorphisms in immune-regulating genes (CTLA-4, PDCD1 and CD274) and susceptibility to nasopharyngeal carcinoma (NPC) in the Tunisian population. We analyzed six polymorphisms: rs231775 and rs3087243 (CTLA-4), rs2227981, rs2227982, and rs36084323 (PDCD1), and rs2890658 (CD274) in a case–control study which enrolled 61 Tunisian NPC patients and 150 matched healthy controls using the PCR-RFLP method.

Results

For the rs231775 SNP, our findings showed a significant association between the AA genotype and increased NPC susceptibility in the recessive model (GG + AG vs. AA) (pc=0.006, OR = 2.5, 95% CI: [1.35–4.6]). Further, the haplotype analysis showed that the rs231775 > A-rs3087243 > A-rs36084323 > G-rs2227982 > C-rs2227981 > C risk haplotype was significantly more expressed in NPC patients (p = 0.044, OR = 1.64, 95% CI: [1.02–2.63]). The phenotype-genotype association revealed that the rs231775 > AA genotype was significantly associated with clinical manifestations. We also confirmed that the rs2890658 > CC genotype was significantly associated with increased risk of NPC under the recessive model (AA + CA vs. CC), p = 0.0001, OR = 3.2, 95% CI: [1.71 − 5.96]. In addition, the rs2890658 > C variant had a 2.4-fold higher risk of NPC in comparison with the A allele (p = 0.0009, OR = 2.4, 95% CI: [1.42 − 4.08]).

Conclusion

Our results suggest that the CTLA-4_rs231775 > AA and CD274_rs2890658 > CC genotypes could be considered as predisposition factors for NPC. These findings could pave the way for future investigations into NPC pathogenesis and assessing CTLA-4, PDCD1, and CD274 as personalized therapeutic targets.