Bhat Imtiyaz A, Naykoo Niyaz A, Qasim Iqbal, Ganie Farooq A, Yousuf Qaiser, Bhat Bashir A, Rasool Roohi, Aziz S A, Shah Zafar Amin
Department of Immunology & Molecular Medicine, Sher-i-Kashmir Institute of Medical Sciences, Srinagar, India.
Department of Animal Biotechnology, Sher-i-Kashmir University of Agricultural Sciences, Srinagar, India.
Meta Gene. 2014 Jan 17;2:123-33. doi: 10.1016/j.mgene.2013.12.002. eCollection 2014 Dec.
Interleukin 1 beta (IL- 1β), a key proinflammatory cytokine encoded by the interleukin 1 beta gene, has been associated with chronic inflammation and plays an important role in lung inflammatory diseases including lung cancer. Elevated levels of Interleukin 1proteins, in particular interleukin 1 beta greatly enhance the intensity of the inflammatory response.
To study the role of interleukin 1 beta-31C > T and -511 T > C polymorphism in the pathogenesis of non small cell lung cancer (NSCLC).
One hundred and ninety non small cell lung cancer patients and 200 healthy age, sex, smoking and dwelling matched controls were used for polymorphic analysis by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by sequencing. Normal tissues of 48 histopathologically confirmed non small cell lung cancer patients were taken for mRNA expression analysis. Quantitation of interleukin 1 beta was carried out by quantitative real time PCR.
The T/T genotype of interleukin 1 beta-31 gene was significantly associated with increased risk of NSCLC [(P = 0.001, OR - 2.8 (95%CI 1.52-5.26)]. The interleukin 1 beta - 511 T > C does not show any difference between the NSCLC and control group (P = 0.3, OR - 0.72 (95%CI 0.41-1.28). Quantitative analysis of mRNA showed significant association with interleukin 1 beta T allele as compared to the interleukin 1 beta-31C allele (P = 0.006).
We conclude that lung cancer risk genotype interleukin 1 beta-31TT results in increased expression of interleukin 1 beta mRNA in lung cancer patients. Our data suggest that this genotype (IL1β -31TT) in the interleukin 1 beta regulatory region provide a microenvironment with elevated inflammatory stimuli and thus increasing the risk for lung cancer.
白细胞介素1β(IL-1β)是由白细胞介素1β基因编码的关键促炎细胞因子,与慢性炎症相关,在包括肺癌在内的肺部炎症性疾病中起重要作用。白细胞介素1蛋白水平升高,尤其是白细胞介素1β,会大大增强炎症反应的强度。
研究白细胞介素1β-31C>T和-511T>C多态性在非小细胞肺癌(NSCLC)发病机制中的作用。
选取190例非小细胞肺癌患者和200例年龄、性别、吸烟和居住情况匹配的健康对照,采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术进行多态性分析,随后进行测序。选取48例经组织病理学确诊的非小细胞肺癌患者的正常组织进行mRNA表达分析。通过定量实时PCR对白细胞介素1β进行定量分析。
白细胞介素1β-31基因的T/T基因型与NSCLC风险增加显著相关[(P = 0.001,OR - 2.8(95%CI 1.52 - 5.26)]。白细胞介素1β-511T>C在NSCLC组和对照组之间未显示出任何差异(P = 0.3,OR - 0.72(95%CI 0.41 - 1.28))。mRNA定量分析显示,与白细胞介素1β-31C等位基因相比,白细胞介素1β T等位基因存在显著相关性(P = 0.006)。
我们得出结论,肺癌风险基因型白细胞介素1β-31TT导致肺癌患者白细胞介素1β mRNA表达增加。我们的数据表明,白细胞介素1β调控区域的这种基因型(IL1β -31TT)提供了一个炎症刺激升高的微环境,从而增加了患肺癌的风险。