AGER rs2070600 polymorphism elevates neutrophil-lymphocyte ratio and mortality in metastatic lung adenocarcinoma
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Kakuhiro Yamaguchi1, Hiroshi Iwamoto1, Shinjiro Sakamoto1, Yasushi Horimasu1, Takeshi Masuda1, Shintaro Miyamoto1, Taku Nakashima1, Shinichiro Ohshimo2, Kazunori Fujitaka1, Hironobu Hamada3 and Noboru Hattori1
1Department of Molecular and Internal Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
2Department of Emergency and Critical Care Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan
3Department of Physical Analysis and Therapeutic Sciences, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan
Hiroshi Iwamoto, email: firstname.lastname@example.org
Keywords: AGER polymorphism, neutrophil-lymphocyte ratio, lung cancer, metastatic adenocarcinoma, disease susceptibility
Received: April 25, 2017 Accepted: September 21, 2017 Published: October 10, 2017
Background: The receptor for advanced glycation end-product (RAGE) is a multi-ligand receptor involved in inflammation. In the gene encoding RAGE (AGER), there are three well-known polymorphisms; rs2070600, rs1800624, and rs1800625, which potentially increase the risk of lung cancer. Remarkably, AGER rs2070600 polymorphism, which increases ligand-binding affinity, is a potential prognostic factor in non-small cell lung cancer, but the underlying mechanism is unclear. The neutrophil-lymphocyte ratio (NLR) reflects tumor-associated systemic inflammatory conditions; high ratios are associated with poor prognosis in multiple cancers. Additionally, some humoral factors via RAGE-signaling are associated with elevated NLR in cancer patients.
Objectives: Associations of AGER polymorphisms with disease susceptibility, prognosis, and NLR were investigated in Japanese patients with lung adenocarcinoma.
Methods: We included 189 patients with lung adenocarcinoma, 96 of which had distant metastases, and 303 healthy controls. The correlation between AGER polymorphisms (rs2070600, rs1800624, rs1800625) and disease susceptibility and factors elevating the mortality and NLR in patients with metastases were evaluated.
Results: Only the minor allele of rs2070600 was associated with a higher NLR (β = 0.209, p = 0.043) and a poor prognosis (Hazard ratio = 2.06, 95% Confidence interval = 1.09–3.77, p = 0.028) in patients with metastatic disease, independently of background characteristics, including EGFR mutation status. All three polymorphisms were not associated with the risk of lung adenocarcinoma.
Conclusions: The AGER rs2070600 polymorphism was independently associated with systemic inflammation and poor prognosis in patients with metastatic lung adenocarcinoma.
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