Association between genetic polymorphisms involved in the hypoxia‐inducible factor pathway and lung cancer risk: a case–control study in Japan

• Published in: Asia-Pacific journal of clinical oncology Vol. 13; no. 3; pp. 234 - 242
• Main Authors: Yamamoto, Yuzo, Kiyohara, Chikako, Ogata‐Suetsugu, Saiko, Hamada, Naoki, Nakanishi, Yoichi
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.06.2017
• Subjects: Aged; Cigarette smoking; Female; Health risk assessment; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Hypoxia-inducible factor 1a; hypoxia‐inducible factor; interaction; Japan; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Middle Aged; Occupational hazards; Polymerase chain reaction; polymorphism; Polymorphism, Genetic - genetics; Smoking; Tumor cells; Vascular endothelial growth factor; lung cancer; interaction; hypoxia-inducible factor; polymorphism; smoking
• ISSN: 1743-7555; 1743-7563
• DOI: 10.1111/ajco.12640

Aim Hypoxia‐inducible factor (HIF) contributes to the adaptation of tumor cells to hypoxic conditions, so genetic polymorphisms involved in this pathway may affect cellular response to hypoxia and be associated with cancer risk. Thus, we examined the association between the lung cancer risk and genetic polymorphisms involved in the HIF pathway. Methods This case–control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of HIF1A rs11549467, HIF1A rs11549465, HIF1A rs2057482, HIF2A rs13419896 and vascular endothelial growth factor A (VEGFA) rs833061 on the risk of lung cancer using TaqMan real‐time PCR assay. Logistic regression was used to estimate the odds ratio (OR) and its 95% confidence interval (CI) of lung cancer risk. The multiplicative and additive interactions with cigarette smoking were also examined. Results The AA genotype of HIF2A rs13419896 (OR = 0.54, 95% CI = 0.30–0.99) and the CC genotype of VEGFA rs833061 (OR = 0.42, 95% CI = 0.24–0.75) were significantly associated with a decreased risk of lung cancer after adjustment of potential covariates. Additive interactions between these two polymorphisms and cigarette smoking were also significant. Conclusion HIF2A rs13419896 and VEGFA rs833061 were significantly related to lung cancer risk, with possible interaction between polymorphisms and cigarette smoking. Further studies are needed to confirm these results.