Background: As being the third‑most common cancer type in males and the second‑most common cancer type in females worldwide, the incidence of colorectal carcinoma is increasing and associated with poor prognosis. Programmed cell death protein 1 (PD-1) gene encodes an inhibitory cell surface receptor that is thought to be implicated in influencing the cancer cells' evasion of the host immune system. The current work was conducted to evaluate the association of PD-1 single nucleotide polymorphisms, PD-1.3G/A (rs11568821) and PD-1.5 C/T (rs2227981) haplotypes with both the susceptibility and the onset of colorectal cancer in the Egyptian population.
Methods and Results: The PD-1.3 G/A and, PD-1.5 C/T polymorphisms were investigated in 100 colorectal cancer patients and 100 healthy controls by allelic discrimination technique through TaqMan real-time polymerase chain reaction. The lowest overall risk of colorectal cancer was associated with the haplotype G/T while the A/T haplotype showed the highest risk among the four being insignificant. However, the A/T haplotype was significantly associated with an increased risk of the early onset disease by 4.4 times as compared to the reference haplotype G/C. Moreover, the PD1.5C/T SNP was in a significant linkage disequilibrium with PD1.3G/A SNP (D = 0.0255, D'= 0.151, r= 0.1298 and p= 0.0094)
Conclusion: Among the Egyptian population, the G/T haplotype was considered protective acquiring the least risk for colorectal cancer, while the mutant A/T haplotype was not only associated with a higher risk of the disease but also with a significantly higher risk to exhibit early-onset colorectal cancer.