title: Polymorphisms of co-inhibitory molecules (CTLA-4/PD-1/PD-L1) and the risk of non-small cell lung cancer in a Chinese population.
abstract: Lung cancer is a leading cause of cancer-related death in China, with non-small cell lung cancer (NSCLC) comprises the most common form. Co-inhibitory molecules, such as cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed death 1 (PD-1) and its ligand PD-L1, play a key roles in the physiopathological process of tumorigenesis. To investigate whether genetic variations of co-inhibitory molecules are associated with the risk of NSCLC, we analyzed polymorphisms of CTLA-4 (-318, +49), PD-1 (PD-1.1, PD-1.3, PD-1.5, PD-1.9) and PD-L1 (+8293) in a cohort of 528 NSCLC subjects and 600 healthy controls. By restriction fragment length polymorphism (RFLP) method, we found that the distributions of the CTLA-4 and PD-1 gene polymorphisms were similar between NSCLC patients and healthy controls. However, for the PD-L1 8923 A/C polymorphism, frequencies of the AC genotype and C-allele were significantly higher in NSCLC patients than in healthy controls (odds ratio [OR] =1.55; 95% confidence interval [CI] 1.13-2.13; P=0.006; OR=1.52; 95% CI 1.14-2.04; P=0.004, respectively). Stratification analysis revealed that prevalence of the 8923C allele was significantly increased in NSCLC patients who smoke compared to those non-smoking patients (OR=1.51; 95% CI 1.00-2.28; P<0.05). Moreover, NSCLC patients carrying the C-allele had higher risk of regional lymph node metastasis than those carrying the A-allele (OR=5.65; 95% CI 2.45~13.03; P<0.001). These data suggest that PD-L1+8293A>C polymorphism may play a role in the development and progression of NSCLC.
authors.affiliation: School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences Jinan 250117, Shandong, China ; Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Xiuchun
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Oncology, Weifang Hospital of Traditional Chinese Medicine Weifang 261000, Shandong, China.
authors.forename: Jingyan
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Wanhu
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Liangjun
authors.initials: L
authors.lastname: Guo
authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Bao
authors.initials: B
authors.lastname: Song
authors.affiliation: School of Medicine and Life Sciences, University of Jinan, Shandong Academy of Medical Sciences Jinan 250117, Shandong, China ; Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Sensen
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences 440 Jiyan Road, Jinan 250117, Shandong, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Jie
keywords: CTLA-4; PD-1; non-small cell lung cancer; polymorphisms