A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer

ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 ge...

Full description

Bibliographic Details
Main Authors:	Campa, Daniele, Sainz, Juan, Pardini, Barbara, Vodickova, Ludmila, Naccarati, Alessio, Rudolph, Anja, Novotny, Jan, Försti, Asta, Buch, Stephan, von Schönfels, Witigo, Schafmayer, Clemens, Völzke, Henry, Hoffmeister, Michael, Frank, Bernd, Barale, Roberto, Hemminki, Kari, Hampe, Jochen, Chang-Claude, Jenny, Brenner, Hermann, Vodicka, Pavel, Canzian, Federico
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292569/

id	pubmed-3292569
recordtype	oai_dc
spelling	pubmed-32925692012-03-06 A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer Campa, Daniele Sainz, Juan Pardini, Barbara Vodickova, Ludmila Naccarati, Alessio Rudolph, Anja Novotny, Jan Försti, Asta Buch, Stephan von Schönfels, Witigo Schafmayer, Clemens Völzke, Henry Hoffmeister, Michael Frank, Bernd Barale, Roberto Hemminki, Kari Hampe, Jochen Chang-Claude, Jenny Brenner, Hermann Vodicka, Pavel Canzian, Federico Research Article ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (Ptrend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (Ptrend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC. Public Library of Science 2012-03-02 /pmc/articles/PMC3292569/ /pubmed/22396794 http://dx.doi.org/10.1371/journal.pone.0032784 Text en Campa et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Campa, Daniele Sainz, Juan Pardini, Barbara Vodickova, Ludmila Naccarati, Alessio Rudolph, Anja Novotny, Jan Försti, Asta Buch, Stephan von Schönfels, Witigo Schafmayer, Clemens Völzke, Henry Hoffmeister, Michael Frank, Bernd Barale, Roberto Hemminki, Kari Hampe, Jochen Chang-Claude, Jenny Brenner, Hermann Vodicka, Pavel Canzian, Federico
spellingShingle	Campa, Daniele Sainz, Juan Pardini, Barbara Vodickova, Ludmila Naccarati, Alessio Rudolph, Anja Novotny, Jan Försti, Asta Buch, Stephan von Schönfels, Witigo Schafmayer, Clemens Völzke, Henry Hoffmeister, Michael Frank, Bernd Barale, Roberto Hemminki, Kari Hampe, Jochen Chang-Claude, Jenny Brenner, Hermann Vodicka, Pavel Canzian, Federico A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
author_facet	Campa, Daniele Sainz, Juan Pardini, Barbara Vodickova, Ludmila Naccarati, Alessio Rudolph, Anja Novotny, Jan Försti, Asta Buch, Stephan von Schönfels, Witigo Schafmayer, Clemens Völzke, Henry Hoffmeister, Michael Frank, Bernd Barale, Roberto Hemminki, Kari Hampe, Jochen Chang-Claude, Jenny Brenner, Hermann Vodicka, Pavel Canzian, Federico
author_sort	Campa, Daniele
title	A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
title_short	A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
title_full	A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
title_fullStr	A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
title_full_unstemmed	A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer
title_sort	comprehensive investigation on common polymorphisms in the mdr1/abcb1 transporter gene and susceptibility to colorectal cancer
description	ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of several carcinogens from the gut. Several polymorphic variants within the ABCB1 gene have been reported as modulators of ABCB1-mediated transport. We investigated the impact of ABCB1 genetic variants on colorectal cancer (CRC) risk. A hybrid tagging/functional approach was performed to select 28 single nucleotide polymorphisms (SNPs) that were genotyped in 1,321 Czech subjects, 699 CRC cases and 622 controls. In addition, six potentially functional SNPs were genotyped in 3,662 German subjects, 1,809 cases and 1,853 controls from the DACHS study. We found that three functional SNPs (rs1202168, rs1045642 and rs868755) were associated with CRC risk in the German population. Carriers of the rs1202168_T and rs868755_T alleles had an increased risk for CRC (Ptrend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (Ptrend = 0.022). We sought to replicate the most significant results in an independent case-control study of 3,803 subjects, 2,169 cases and 1,634 controls carried out in the North of Germany. None of the SNPs tested were significantly associated with CRC risk in the replication study. In conclusion, in this study of about 8,800 individuals we show that ABCB1 gene polymorphisms play at best a minor role in the susceptibility to CRC.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3292569/
_version_	1611510155427446784

A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer

Similar Items