SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.

<h4>Purpose</h4>Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of...

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Autores principales:	Qianxia Li, Huanlei Wu, Bei Chen, Guangyuan Hu, Liu Huang, Kai Qin, Yu Chen, Xianglin Yuan, Zhongxing Liao
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/276f5778c603493896b48ef50f092c21
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spelling	oai:doaj.org-article:276f5778c603493896b48ef50f092c212021-11-18T08:04:48ZSNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.1932-620310.1371/journal.pone.0051713https://doaj.org/article/276f5778c603493896b48ef50f092c212012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23284751/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Purpose</h4>Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis.<h4>Patients and methods</h4>We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis.<h4>Results</h4>The median age of the 116 men and 45 women in the study was 58 years; 62 (39%) had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%). Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024), compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001).<h4>Conclusions</h4>We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis.Qianxia LiHuanlei WuBei ChenGuangyuan HuLiu HuangKai QinYu ChenXianglin YuanZhongxing LiaoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 12, p e51713 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Qianxia Li Huanlei Wu Bei Chen Guangyuan Hu Liu Huang Kai Qin Yu Chen Xianglin Yuan Zhongxing Liao SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
description	<h4>Purpose</h4>Brain metastasis (BM) from non-small cell lung cancer (NSCLC) is relatively common, but identifying which patients will develop brain metastasis has been problematic. We hypothesized that genotype variants in the TGF-β signaling pathway could be a predictive biomarker of brain metastasis.<h4>Patients and methods</h4>We genotyped 33 SNPs from 13 genes in the TGF-β signaling pathway and evaluated their associations with brain metastasis risk by using DNA from blood samples from 161 patients with NSCLC. Kaplan-Meier analysis was used to assess brain metastasis risk; Cox hazard analyses were used to evaluate the effects of various patient and disease characteristics on the risk of brain metastasis.<h4>Results</h4>The median age of the 116 men and 45 women in the study was 58 years; 62 (39%) had stage IIIB or IV disease. Within 24 months after initial diagnosis of lung cancer, brain metastasis was found in 60 patients (37%). Of these 60 patients, 16 had presented with BM at diagnosis. Multivariate analysis showed the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with a significantly higher risk of brain metastasis at 24 months follow-up (hazard ratio [HR] 2.540, 95% confidence interval [CI] 1.204-5.359, P = 0.014; and HR 1.885, 95% CI 1.086-3.273, P = 0.024), compared with the GA or CT/CC genotypes, respectively. When we analyzed combined subgroups, these rates showed higher for those having both the GG genotype of SMAD6: rs12913975 and the TT genotype of INHBC: rs4760259 (HR 2.353, 95% CI 1.390-3.985, P = 0.001).<h4>Conclusions</h4>We found the GG genotype of SMAD6: rs12913975 and TT genotype of INHBC: rs4760259 to be associated with risk of brain metastasis in patients with NSCLC. This finding, if confirmed, can help to identify patients at high risk of brain metastasis.
format	article
author	Qianxia Li Huanlei Wu Bei Chen Guangyuan Hu Liu Huang Kai Qin Yu Chen Xianglin Yuan Zhongxing Liao
author_facet	Qianxia Li Huanlei Wu Bei Chen Guangyuan Hu Liu Huang Kai Qin Yu Chen Xianglin Yuan Zhongxing Liao
author_sort	Qianxia Li
title	SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
title_short	SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
title_full	SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
title_fullStr	SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
title_full_unstemmed	SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
title_sort	snps in the tgf-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/276f5778c603493896b48ef50f092c21
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SNPs in the TGF-β signaling pathway are associated with increased risk of brain metastasis in patients with non-small-cell lung cancer.

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