Journal
JOURNAL OF THORACIC ONCOLOGY
Volume 9, Issue 11, Pages 1709-1713Publisher
ELSEVIER SCIENCE INC
DOI: 10.1097/JTO.0000000000000309
Keywords
Lung adenocarcinoma; EPAS1; HIF-2; SNP
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Funding
- Grants-in-Aid for Scientific Research [221S0001] Funding Source: KAKEN
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Introduction: Hypoxia-inducible factor-2 (also called endothelial periodic acid-Schiff domain protein 1 [EPAS1]) seems to play an important role in some carcinogenesis, though there is no information on the relationship between single nucleotide polymorphism of EPAS1 and lung cancer development. The aim of this study was to explore a possible association of the EPAS1 gene rs4953354 polymorphism with susceptibility to lung cancer. Methods: A case-control study of 346 patients with non-small-cell lung carcinoma (adenocarcinoma = 249, squamous cell carcinoma = 97) and 247 healthy control subjects was carried out. A/G polymorphism within an intron 2 of the EPAS1 (rs4953354) was determined by direct sequencing. Results: A frequency of lung adenocarcinoma patients with a minor allele G (A/G or G/G genotype) at the rs4953354 was much higher than that of controls (odds ratio, 1.800; 95% confidence interval, 1.161-2.791; p = 0.008). This association was more evident when analyzed using female never-smokers (odds ratio, 3.31; 95% confidence interval, 1.21-9.01; p = 0.017). Mutations in epidermal growth factor receptor tended to be frequent in patients with G allele at the rs4953354, compared with those with other genotypes. Conclusion: The EPAS1 rs4953354 may be a potentially susceptible marker for development of lung adenocarcinoma, especially in female never-smokers.
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