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A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker

Pregnane X receptor (PXR) is an important member of the nuclear receptor superfamily that copes with various endobiotic and xenobiotic stimuli, such as carcinogens by regulating an array of environmental response genes. Low PXR expression has been shown to promote tumor initiation and metastasis. Th...

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Autores principales: Zhang, Lisha, Qiu, Fuman, Lu, Xiaoxiao, Li, Yinyan, Fang, Wenxiang, Zhang, Lan, Zhou, Yifeng, Yang, Lei, Lu, Jiachun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2014
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227172/
https://www.ncbi.nlm.nih.gov/pubmed/25268617
http://dx.doi.org/10.3390/ijms151017457
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author Zhang, Lisha
Qiu, Fuman
Lu, Xiaoxiao
Li, Yinyan
Fang, Wenxiang
Zhang, Lan
Zhou, Yifeng
Yang, Lei
Lu, Jiachun
author_facet Zhang, Lisha
Qiu, Fuman
Lu, Xiaoxiao
Li, Yinyan
Fang, Wenxiang
Zhang, Lan
Zhou, Yifeng
Yang, Lei
Lu, Jiachun
author_sort Zhang, Lisha
collection PubMed
description Pregnane X receptor (PXR) is an important member of the nuclear receptor superfamily that copes with various endobiotic and xenobiotic stimuli, such as carcinogens by regulating an array of environmental response genes. Low PXR expression has been shown to promote tumor initiation and metastasis. The aim of the current study was to investigate whether the single nucleotide polymorphisms (SNPs) of PXR could alter lung cancer susceptibility in Chinese by affecting the function or expression of PXR. We genotyped three putatively functional SNPs of PXR (i.e., rs3814055C>T, rs3732360C>T, and rs3814058C>T) and analyzed their associations with lung cancer risk in a two-stage case-control study with a total of 1559 lung cancer cases and 1679 controls in the southern and eastern Chinese population. We found that in comparison to the rs3814058CC common genotype, the rs3814058T variants (TC/TT) which is located in the 3'-untranslated region (3'-UTR) of PXR conferred a consistently increased risk of lung cancer in both the southern Chinese (odd ratios (OR) = 1.24, 95% confidence interval (CI) = 1.03−1.49) and the eastern Chinese (OR = 1.33, 95% CI = 1.02−1.75). The variants also significantly interacted with smoking on increasing cancer risk (p = 0.023). Moreover, lung cancer tissues with the rs3814058T variants showed significantly lower PXR expression than those with rs3814058CC genotype in the smokers (p = 0.041). These results suggested that the rs3814058C>T polymorphism of PXR interacts with smoking on increasing lung cancer risk in Chinese smokers, which might be a functional genetic biomarker for lung cancer.
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spelling pubmed-42271722014-11-12 A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker Zhang, Lisha Qiu, Fuman Lu, Xiaoxiao Li, Yinyan Fang, Wenxiang Zhang, Lan Zhou, Yifeng Yang, Lei Lu, Jiachun Int J Mol Sci Article Pregnane X receptor (PXR) is an important member of the nuclear receptor superfamily that copes with various endobiotic and xenobiotic stimuli, such as carcinogens by regulating an array of environmental response genes. Low PXR expression has been shown to promote tumor initiation and metastasis. The aim of the current study was to investigate whether the single nucleotide polymorphisms (SNPs) of PXR could alter lung cancer susceptibility in Chinese by affecting the function or expression of PXR. We genotyped three putatively functional SNPs of PXR (i.e., rs3814055C>T, rs3732360C>T, and rs3814058C>T) and analyzed their associations with lung cancer risk in a two-stage case-control study with a total of 1559 lung cancer cases and 1679 controls in the southern and eastern Chinese population. We found that in comparison to the rs3814058CC common genotype, the rs3814058T variants (TC/TT) which is located in the 3'-untranslated region (3'-UTR) of PXR conferred a consistently increased risk of lung cancer in both the southern Chinese (odd ratios (OR) = 1.24, 95% confidence interval (CI) = 1.03−1.49) and the eastern Chinese (OR = 1.33, 95% CI = 1.02−1.75). The variants also significantly interacted with smoking on increasing cancer risk (p = 0.023). Moreover, lung cancer tissues with the rs3814058T variants showed significantly lower PXR expression than those with rs3814058CC genotype in the smokers (p = 0.041). These results suggested that the rs3814058C>T polymorphism of PXR interacts with smoking on increasing lung cancer risk in Chinese smokers, which might be a functional genetic biomarker for lung cancer. MDPI 2014-09-29 /pmc/articles/PMC4227172/ /pubmed/25268617 http://dx.doi.org/10.3390/ijms151017457 Text en © 2014 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Lisha
Qiu, Fuman
Lu, Xiaoxiao
Li, Yinyan
Fang, Wenxiang
Zhang, Lan
Zhou, Yifeng
Yang, Lei
Lu, Jiachun
A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker
title A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker
title_full A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker
title_fullStr A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker
title_full_unstemmed A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker
title_short A Functional Polymorphism in the 3'-UTR of PXR Interacts with Smoking to Increase Lung Cancer Risk in Southern and Eastern Chinese Smoker
title_sort functional polymorphism in the 3'-utr of pxr interacts with smoking to increase lung cancer risk in southern and eastern chinese smoker
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4227172/
https://www.ncbi.nlm.nih.gov/pubmed/25268617
http://dx.doi.org/10.3390/ijms151017457
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