title: PD-1gene promoter polymorphisms correlate with a poor prognosis in non-small cell lung cancer.
abstract: 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. ThePD-1SNP 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 ofPD-1was 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 ofPD-1was 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-1may 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.
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Hidefumi
authors.initials: H
authors.lastname: Sasaki
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Tatemaysu
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Katsuhiro
authors.initials: K
authors.lastname: Okuda
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Moriyama
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Motoki
authors.initials: M
authors.lastname: Yano
authors.affiliation: Department of Oncology, Immunology and Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Fujii
keywords: immunotherapy; lung cancer; prognosis; programmed death 1; squamous cell carcinomas