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Oncol Lett. 2017 May;13(5):3873-3881. doi: 10.3892/ol.2017.5867. Epub 2017 Mar 17.

Biological interaction of cigarette smoking on the association between genetic polymorphisms involved in inflammation and the risk of lung cancer: A case-control study in Japan.

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Research Institute for Diseases of The Chest, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan.


Chronic inflammation serves an important role in lung carcinogenesis, thus genetic polymorphisms involved in this pathway may affect the risk of lung cancer. The present case-control study focused on the association between lung cancer risk and genetic polymorphisms involved in inflammatory pathways. The study comprised 462 lung cancer cases and 379 controls from Japan. The roles of interleukin 8 (IL8) rs4073, nuclear factor kappa B (NFκB) rs28362491, cytochrome b-245, alpha polypeptide (CYBA) rs4673, NAD(P) H dehydrogenase, quinone 1 (NQO1) rs1800566, nitric oxide synthase 2 and inducible (NOS2) rs2297518 polymorphisms in lung carcinogenesis were investigated. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between the genetic polymorphisms and lung cancer risk. The multiplicative and additive [relative excess risk due to interaction, attributable proportion due to interaction (AP) and synergy index (SI)] interactions with cigarette smoking were also determined. A significant association was revealed between the TT genotype of NQO1 rs1800566 and an increased risk of lung cancer (OR=1.78; 95% CI=1.14-2.79). The additive interaction evaluations between CYBA rs4673 (AP=0.50, 95% CI=0.15-0.85; SI=2.66, 95% CI=1.01-6.99) and smoking were also statistically significant. NQO1 rs1800566 was significantly associated with lung cancer risk and smoking may influence the association between CYBA rs4673 and the risk of lung cancer. Additional studies with larger control and case populations are warranted in order to confirm the CYBA rs4673-smoking association suggested by the present study.


inflammation; interaction; lung cancer; polymorphism; smoking

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