Genetic polymorphisms in the endothelial nitric oxide synthase gene correlate with overall survival in advanced non-small-cell lung cancer patients treated with platinum-based doublet chemotherapyReportar como inadecuado




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BMC Medical Genetics

, 11:167

First Online: 30 November 2010Received: 14 April 2010Accepted: 30 November 2010

Abstract

BackgroundNitric oxide NO is a free radical that is involved in carcinogenesis. Endothelial NO, synthesized from L-arginine by endothelial NO synthase eNOS, inhibits apoptosis and promotes angiogenesis, tumor cell proliferation and metastasis. The aim of this study was to evaluate the influence of polymorphisms in the eNOS gene on prognosis of patients with advanced stage non-small-cell lung cancer NSCLC.

MethodsUnresectable, chemotherapy naïve stage III or IV NSCLC patients who were treated with standard platinum-containing doublet regimens were analyzed. All individuals were genotyped for the single-nucleotide polymorphism G894T in exon 7 of the eNOS gene and for a variable number of tandem repeats VNTR polymorphism in intron 4 that results in a rare smaller allele a and a common larger allele b, to investigate the association between these polymorphisms and clinical outcomes. The primary endpoint was correlation with overall survival.

ResultsFrom October 2004 to December 2007, 108 patients male-female, 66-42; Stage IIIA-IIIB-IV, 6-30-72 aged 29-77 years median 63 with good performance status were consecutively enrolled in this study. Using Kaplan-Meier estimates, we showed that 5-year overall survival was significantly increased in patients carrying the VNTR a-allele compared with VNTR b-b patients P = 0.015. In multivariate Cox proportional hazard analysis, the VNTR polymorphism was an independent prognostic factor for survival.

ConclusionsThe results support the role of the VNTR polymorphism in intron 4 as a marker for survival in patients with advanced stage NSCLC who are candidates for standard chemotherapy.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-11-167 contains supplementary material, which is available to authorized users.

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Autor: Shiro Fujita - Katsuhiro Masago - Yukimasa Hatachi - Akiko Fukuhara - Akito Hata - Reiko Kaji - Young Hak Kim - Tadashi M

Fuente: https://link.springer.com/







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