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Association of PD-1 and PDL-1 gene polymorphisms with colorectal cancer risk and prognosis

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Abstract

Background

Programmed Cell Death-1 (PD-1) together with Programmed Death Ligand 1 (PDL-1) have crucial roles in anti-tumor immune response, cancer susceptibility and prognosis. Since PD-1 and PDL-1 have been considered as important genetic risk factors in cancer development and their functions can be affected by polymorphic sites, we investigated the effects of PD-1 rs2227981, rs2227982, rs36084323 and PDL-1 rs2282055, rs822336 gene polymorphisms on colorectal cancer (CRC) risk and prognosis in Turkish subjects.

Methods and results

Our study group consisted of 5-FU or Capacitabine prescribed CRC diagnosed patients and healthy controls. Genotype analyses of PD1 and PDL-1 polymorphisms were performed with Agena MassARRAY platform. rs36084323 CT genotype frequency was found to be higher in controls compared to cases (p < 0.001). rs36084323 CT genotype was highly associated with reduced CRC risk compared to CC genotype (OR 0.068, 95% CI 0.022–0.211, p < 0.001). In adjusted analysis, rs2282055 GG genotype was found to be associated with reduced CRC risk (OR 0.271, 95% CI 0.078–0.940, p = 0.040). rs2282055 TT genotype was found to be related to longer progression-free (Bonferroni corrected Log rank p = 0.013) and overall survival (Bonferroni corrected Log rank p = 0.009) to that of GG genotypes. Patients with rs822336 GC+CC genotypes showed longer overall survival times compared to GG (Log rank p = 0.044).

Conclusions

According to our results, PD-1 rs822336 G > C polymorphism might be useful in predicting CRC prognosis. PDL-1 rs2282055 T > G polymorphism might be useful in predicting both CRC risk and prognosis. Further studies should be conducted in larger and different populations to clear the roles of PD-1 and PDL-1 polymorphisms in CRC risk and prognosis.

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Funding

This study was supported by Marmara University Scientific Research Projects Coordination Unit. Project No. FEN-C-DRP-110718-0407.

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Authors and Affiliations

  1. Department of Molecular Biology, Marmara University Faculty of Arts and Science, Istanbul, Turkey

    Mehtap Cevik & Belgin Susleyici

  2. Department of Medical Oncology, Demiroglu Bilim University Faculty of Medicine, Istanbul, Turkey

    Esat Namal & Nur Dinc-Sener

  3. Istanbul Bagcilar Training and Research Hospital, Istanbul, Turkey

    Ulkuhan Iner-Koksal

  4. Department of Medical Pharmacology, Marmara University School of Medicine, Istanbul, Turkey

    Atila Karaalp

  5. Department of Cardiology, Demiroglu Bilim University Faculty of Medicine, Istanbul, Turkey

    Cavlan Ciftci

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  1. Mehtap Cevik
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Contributions

MC contributed to the experimental molecular genetic analysis, study design and literature. EN, UIK, NDS and CC as the clinicians selected and provided the blood samples and clinical data of subjects to participate in this study. AK contributed to the interpretation and evaluation of the results. BS contributed to the whole study management, development of the final protocol of the experiments, interpretation of the results and organization of the manuscript. All authors were involved in preparing the manuscript.

Corresponding author

Correspondence to Belgin Susleyici.

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No conflict of interest was declared by the authors.

Ethical approval

The experimental protocol was established, according to the ethical guidelines of the Helsinki Declaration and was approved by Marmara University Local Ethical Committee with the protocol number 09.2018.174.

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Written informed consents were obtained from all patients prior to recruitment and sample collection. The study was performed in accordance with the Declaration of Helsinki.

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Cevik, M., Namal, E., Iner-Koksal, U. et al. Association of PD-1 and PDL-1 gene polymorphisms with colorectal cancer risk and prognosis. Mol Biol Rep 49, 1827–1836 (2022). https://doi.org/10.1007/s11033-021-06992-9

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