PD-1 gene promoter polymorphisms correlate with a poor prognosis in non-small cell lung cancer

An imbalance to the regulation of the immune system changes the tumor-specific T-cell immunity in the cancer microenvironment and adjusts the tumor progression and metastasis. Inhibiting the interactions of the immune function mediates the antitumor activity in preclinical models. The programmed death 1 (PD-1) gene -606 G/A polymorphism, which may modify promoter activity and is Asian-specific, was investigated by TaqMan quantitative polymerase chain reaction assay in surgically treated non-small cell lung cancer (NSCLC) cases. In the present study, 583 surgically removed NSCLC cases were included for single-nucleotide polymorphism (SNP) analyses. The PD-1 SNP statuses at the promoter region (rs36084323) were 146 AA (25.0%), 293 GA (50.3%) and 144 GG (24.7%). The ratio was extremely similar to the healthy control in a previous study: 24.9% AA, 47.8% GA and 27.3% GG. The ratio of the GG phenotype was not significantly different for gender (25.1% males and 23.9% female), age (25.2% <= 65 years and 24.4% >65 years), smoking status (26.1% smoker and 21.8% non-smoker) and pathological subtypes [25.4% adenocarcinoma (adeno) and 24.2% squamous cell carcinoma (SCC)]. The GG ratio of PD-1 was not significantly different between pathological stage II-IV (25.5%) and stage I cases (24.1%; P=0.6245). The survival time of the patients with the -606 GG phenotype of PD-1 was significantly lower (n=147, 50 succumbed) compared to the patients with -606 GA or -606 AA (n=435, 109 succumbed) (P=0.0183). The GG phenotype patients had a significantly worse prognosis in the SCC population (P=0.009), however, this was not different to the adeno population (P=0.2594). Thus, PD-1 may promote tumor prognosis and provide a candidate for the blockade of its function as a strategy to antagonize the progression process in NSCLC, particularly lung SCC.