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

0379739 - ÚEM 2013 RIV US eng J - Journal Article
Campa, D. - Sainz, J. - Pardini, Barbara - Vodičková, Ludmila - Naccarati, Alessio - Rudolph, A. - Novotný, J. - Försti, A. - Buch, S. - von Schönfels, W. - Schafmayer, C. - Völzke, H. - Hoffmeister, M. - Frank, B. - Barale, R. - Hemminki, K. - Hampe, J. - Chang-Claude, J. - Brenner, H. - Vodička, Pavel - Canzian, F.
A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer.
PLoS ONE. Roč. 7, č. 3 (2012), e32784. ISSN 1932-6203. E-ISSN 1932-6203
R&D Projects: GA ČR GA310/07/1430; GA ČR GAP304/10/1286
Institutional research plan: CEZ:AV0Z50390703
Keywords : single-nucleotide polymorphisms * resistance 1 mdr1 * p-glycoprotein
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.730, year: 2012

ATP Binding Cassette B1 (ABCB1) is a transporter with a broad substrate specificity involved in the elimination of carcinogens from the gut. 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 1,321Czech 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 a minor role in the susceptibility to CRC.
Permanent Link: http://hdl.handle.net/11104/0210624