The effect of lysyl oxidase polymorphism on susceptibility and prognosis of nonsmall cell lung cancer
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RESEARCH ARTICLE
The effect of lysyl oxidase polymorphism on susceptibility and prognosis of nonsmall cell lung cancer Weiwei Shi & Bo Yang & Xiaoyan Li & Shengjie Sun & Lijie Wang & Shunchang Jiao
Received: 23 June 2012 / Accepted: 22 August 2012 / Published online: 5 September 2012 # International Society of Oncology and BioMarkers (ISOBM) 2012
Abstract Lysyl oxidase (LOX) is a copper-dependent amine oxidase that plays important roles in development and homeostasis of the lungs. The aim of this study was to investigate whether polymorphisms in the LOX gene were associated with susceptibility to nonsmall cell lung cancer (NSCLC). We sequenced the promoter region of LOX gene and tested the previously reported polymorphism 473 G/A in the Han Chinese population. A novel polymorphism, −22 G/C, was identified in the promoter region of LOX. However, it did not show any correlation with NSCLC. Frequencies of the 473AA genotype and 473A allele were significantly higher in the NSCLC cases than in control group (p00.004 and p00.006, respectively). Further, our results showed that survival time of NSCLC patients with 473AA genotype was significantly shorter compared to the cases carrying 473 G allele (20.0 months vs. 28.0 months, p00.011). These data indicate that LOX 473 G/A polymorphism is associated with increased risk of NSCLC and can be a prognostic predictor for this disease. Keywords Lysyl oxidase . Polymorphism . Non-small cell lung cancer
W. Shi : B. Yang : S. Sun : L. Wang : S. Jiao (*) Department of Oncology, PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853, China e-mail: [email protected] X. Li Department of Lung Cancer, Affiliated Hospital of Academy of Military Medical Sciences, PLA, 8 Dongdajie Road, Fengtai District, Beijing 100071, China
Introduction Lung cancer is the leading cause of cancer mortality worldwide; more than a million people die from this disease each year [1]. Nonsmall cell lung cancer (NSCLC) accounts for up to 80 % of all lung cancer cases. Despite the development of antitumor therapy, prognosis for patients with lung cancer remains poor, with a 5-year survival rate of less than 20 % [1]. Recent studies have provided evidence that genetic factors may influence the course of the disease and survival of patients with NSCLC [2, 3]. Lysyl oxidase (LOX) is a copper-dependent amine oxidase encoded by members of a five-gene family that includes LOX and four LOX-like proteins (LOXL1–4). LOX is synthesized as a 48-kilodalton (kDa) pre–proenzyme and then Nglycosylated and secreted from the cell as a 50-kDa proenzyme. The proenzyme is cleaved extracellularly by bone morphogenetic protein-1 (BMP-1) into the mature 32-kDa LOX protein and an 18-kDa propeptide (LOX-PP) [4]. The critical role played by LOX in the development and homeostasis of the lung is reflected in the disruption of lung structure in chick and rat models of dietary copper deficiency [5, 6]. Markedly decreased levels of LOX seen in these models were consistent with the accompanying reduction in insoluble lun
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