Cargando…

The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies

BACKGROUND: The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by the way of an ATP-dependent cellular efflux mechanism. Three polymorphisms of MDR1, 3435C > T located...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Ling-Hui, Song, Yan-Bin, Zheng, Wen-Ling, Jiang, Ling, Ma, Wen-Li
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669001/
https://www.ncbi.nlm.nih.gov/pubmed/23687985
http://dx.doi.org/10.1186/1475-2867-13-46
_version_ 1782271680943489024
author Wang, Ling-Hui
Song, Yan-Bin
Zheng, Wen-Ling
Jiang, Ling
Ma, Wen-Li
author_facet Wang, Ling-Hui
Song, Yan-Bin
Zheng, Wen-Ling
Jiang, Ling
Ma, Wen-Li
author_sort Wang, Ling-Hui
collection PubMed
description BACKGROUND: The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by the way of an ATP-dependent cellular efflux mechanism. Three polymorphisms of MDR1, 3435C > T located in exon 26, 1236C > T in exon 12 and 2677G > T/A in exon 21 were the most extensively studied and were identified functionally important and ethnically diverse mapping to the gene region. Considering the potential influence of altering MDR1 activity, it is plausible that MDR1 polymorphisms might play a role in the development of cancer. Although the effects of MDR1 polymorphisms on susceptibility to human cancer have been investigated in many studies, the results still remain conflicting. METHODS: To resolve these conflicts, we performed a quantitative synthesis of the association between these three polymorphisms and cancer risk, including 52 studies (15789 cases and 20274 controls) for 3435C > T polymorphism, 10 studies (2101 cases and 2842 controls) for 1236C > T polymorphism and 18 studies (3585 cases and 4351 controls) for 2677G > T/A polymorphism. RESULTS: The stratified analyses for 3435C > T polymorphism, individuals with T-allele in 3435C > T had significantly higher ALL risks (TT versus CC: OR =1.286, 95% CI =1.123-1.474); significantly elevated risks were observed among Caucasian populations (TT versus CC: OR =1.276, 95% CI =1.112-1.464). When restricting the analysis to the source of controls, we found that HB (hospital-based) genetic models had higher risks (TT versus CC: OR =1.307, 95% CI =1.046-1.632), as well as in PB (population-based) genetic models (TT versus CC: OR =1.294, 95% CI =1.079-1.55). The T/A-allele frequency of 2677G > T/A polymorphism was associated with higher risk of cancer (TT + TA + AA vs. GG: OR =1.348, 95% CI =1.031-1.762), significantly elevated risks were observed among Asian populations (TT + TA + AA vs. GG: OR =1.642, 95% CI =1.340-2.012), and elevated risks could be associated with PB models (TT + TA + AA vs. GG: OR =1.641, 95% CI =1.018-2.646). CONCLUSIONS: Our meta-analysis suggested that 3435C > T polymorphism and 2677G > T/A polymorphism were associated with cancer risk when all studies were pooled together, while 1236C > T polymorphism not.
format Online
Article
Text
id pubmed-3669001
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-36690012013-06-01 The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies Wang, Ling-Hui Song, Yan-Bin Zheng, Wen-Ling Jiang, Ling Ma, Wen-Li Cancer Cell Int Primary Research BACKGROUND: The multidrug resistance (MDR) 1 gene encodes a 170-kDa membrane transporter called P-glycoprotein, which plays an important role in protecting cells against lipophilic xenobiotics by the way of an ATP-dependent cellular efflux mechanism. Three polymorphisms of MDR1, 3435C > T located in exon 26, 1236C > T in exon 12 and 2677G > T/A in exon 21 were the most extensively studied and were identified functionally important and ethnically diverse mapping to the gene region. Considering the potential influence of altering MDR1 activity, it is plausible that MDR1 polymorphisms might play a role in the development of cancer. Although the effects of MDR1 polymorphisms on susceptibility to human cancer have been investigated in many studies, the results still remain conflicting. METHODS: To resolve these conflicts, we performed a quantitative synthesis of the association between these three polymorphisms and cancer risk, including 52 studies (15789 cases and 20274 controls) for 3435C > T polymorphism, 10 studies (2101 cases and 2842 controls) for 1236C > T polymorphism and 18 studies (3585 cases and 4351 controls) for 2677G > T/A polymorphism. RESULTS: The stratified analyses for 3435C > T polymorphism, individuals with T-allele in 3435C > T had significantly higher ALL risks (TT versus CC: OR =1.286, 95% CI =1.123-1.474); significantly elevated risks were observed among Caucasian populations (TT versus CC: OR =1.276, 95% CI =1.112-1.464). When restricting the analysis to the source of controls, we found that HB (hospital-based) genetic models had higher risks (TT versus CC: OR =1.307, 95% CI =1.046-1.632), as well as in PB (population-based) genetic models (TT versus CC: OR =1.294, 95% CI =1.079-1.55). The T/A-allele frequency of 2677G > T/A polymorphism was associated with higher risk of cancer (TT + TA + AA vs. GG: OR =1.348, 95% CI =1.031-1.762), significantly elevated risks were observed among Asian populations (TT + TA + AA vs. GG: OR =1.642, 95% CI =1.340-2.012), and elevated risks could be associated with PB models (TT + TA + AA vs. GG: OR =1.641, 95% CI =1.018-2.646). CONCLUSIONS: Our meta-analysis suggested that 3435C > T polymorphism and 2677G > T/A polymorphism were associated with cancer risk when all studies were pooled together, while 1236C > T polymorphism not. BioMed Central 2013-05-20 /pmc/articles/PMC3669001/ /pubmed/23687985 http://dx.doi.org/10.1186/1475-2867-13-46 Text en Copyright © 2013 Wang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Primary Research
Wang, Ling-Hui
Song, Yan-Bin
Zheng, Wen-Ling
Jiang, Ling
Ma, Wen-Li
The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies
title The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies
title_full The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies
title_fullStr The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies
title_full_unstemmed The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies
title_short The association between polymorphisms in the MDR1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies
title_sort association between polymorphisms in the mdr1 gene and risk of cancer: a systematic review and pooled analysis of 52 case–control studies
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669001/
https://www.ncbi.nlm.nih.gov/pubmed/23687985
http://dx.doi.org/10.1186/1475-2867-13-46
work_keys_str_mv AT wanglinghui theassociationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT songyanbin theassociationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT zhengwenling theassociationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT jiangling theassociationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT mawenli theassociationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT wanglinghui associationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT songyanbin associationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT zhengwenling associationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT jiangling associationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies
AT mawenli associationbetweenpolymorphismsinthemdr1geneandriskofcancerasystematicreviewandpooledanalysisof52casecontrolstudies