Abstract
ObjectivesLung cancer in never-smokers is a distinct disease associated with a different genomic landscape, pathogenesis, risk factors, and immune checkpoint inhibitor responses compared to those observed in smokers. This study aimed to identify novel single nucleotide polymorphisms (SNPs) of programmed death-1 (encoded by PDCD1) and its ligands, programmed death ligand 1 (CD274) and 2 (PDCD1LG2), associated with lung cancer risk in never-smoking women.Materials and MethodsDuring September 2002 and July 2012, we enrolled never-smoking female patients with lung adenocarcinoma (LUAD) (n=1153) and healthy women (n=1022) from six tertiary hospitals in Taiwan. SNP data were obtained and analyzed from the genome-wide association study dataset and through an imputation method. The expression quantitative trait loci (eQTL) analysis was performed in both tumor and non-tumor tissues for the correlation between genetic expression and identified SNPs.ResultsA total of 12 PDCD1LG2 SNPs related to LUAD risk were identified in never-smoking women, including rs2381282, rs4742103, rs4237162, rs4742104, rs12237624, rs78096119, rs6476988, rs7857315, rs10975178, rs7854413, rs56001683, and rs7858319. Among them, six tagged PDCD1LG2 SNPs rs2381282, rs4742103, rs4237162, rs4742104, rs78096119, and rs56001683 were significantly associated with LUAD risk. Specifically, two PDCD1LG2 SNPs, rs12237624 and rs78096119, were associated with previous pulmonary tuberculosis infection in relation to LUAD susceptibility. Through an eQTL assay, we found that rs2381282 (p < 0.001), rs12237624 (p = 0.019), and rs78096119 (p = 0.019) were associated with the expression levels of programed death ligand 2.ConclusionsNovel SNPs of programed death ligand 2 associated with lung adenocarcinoma risk were identified. Among them, two SNPs were associated with pulmonary tuberculosis infection in relation to lung adenocarcinoma susceptibility. These SNPs may help to stratify high-risk populations of never-smokers during lung cancer screening.
Highlights
Lung cancer is a growing global health concern [1], and cigarette smoking is a well-known risk factor for lung carcinogenesis [2]
A significant association with lung adenocarcinoma (LUAD) risk was observed for low education levels (p < 0.001), any first-degree family member with a history of lung cancer (p < 0.001), previous pulmonary TB infection (p < 0.001), cooking time in years (p = 0.037), cooking fume exposure (p < 0.001), and exposure to environmental tobacco smoking (ETS) from relatives or workplace (p < 0.001) (Table 1)
PDCD1LG2 single nucleotide polymorphism (SNP) Are Associated With LUAD Risk
Summary
Lung cancer is a growing global health concern [1], and cigarette smoking is a well-known risk factor for lung carcinogenesis [2]. Approximately 25% of lung cancer cases are not attributable to tobacco smoking, and over 50% of female patients have been reported as never-smokers [3, 4]. In Taiwan, more than 90% of female lung cancer patients are never-smokers [6, 7]. Lung cancer in never smokers is considered a distinct disease entity with a proteogenomic landscape and oncogenic mechanisms different from those in smokers [8]. Identifying genetic and environmental factors associated with lung cancer risk in neversmokers is urgently needed, especially in Asia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
