Mehtap Cevik1, Esat Namal2, Ulkuhan Iner-Koksal3, Nur Dinc-Sener2, Atila Karaalp4, Cavlan Ciftci5, Belgin Susleyici6. 1. Department of Molecular Biology, Marmara University Faculty of Arts and Science, Istanbul, Turkey. 2. Department of Medical Oncology, Demiroglu Bilim University Faculty of Medicine, Istanbul, Turkey. 3. Istanbul Bagcilar Training and Research Hospital, Istanbul, Turkey. 4. Department of Medical Pharmacology, Marmara University School of Medicine, Istanbul, Turkey. 5. Department of Cardiology, Demiroglu Bilim University Faculty of Medicine, Istanbul, Turkey. 6. Department of Molecular Biology, Marmara University Faculty of Arts and Science, Istanbul, Turkey. belginsusleyici@gmail.com.
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.
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.
Authors: G J Freeman; A J Long; Y Iwai; K Bourque; T Chernova; H Nishimura; L J Fitz; N Malenkovich; T Okazaki; M C Byrne; H F Horton; L Fouser; L Carter; V Ling; M R Bowman; B M Carreno; M Collins; C R Wood; T Honjo Journal: J Exp Med Date: 2000-10-02 Impact factor: 14.307