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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 LU ; Buch, Stephan and von Schoenfels, Witigo, et al. (2012) In PLoS ONE 7(3).
Abstract
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... (More)
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 (P-trend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (P-trend = 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. (Less)
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PLoS ONE
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7
issue
3
publisher
Public Library of Science
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  • wos:000303006500034
  • scopus:84857718978
ISSN
1932-6203
DOI
10.1371/journal.pone.0032784
language
English
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yes
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551b4594-e109-49a1-b602-10114c345ec2 (old id 2571182)
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2012-06-01 08:54:14
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@article{551b4594-e109-49a1-b602-10114c345ec2,
  abstract     = {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 (P-trend = 0.016 and 0.029, respectively), while individuals bearing the rs1045642_C allele showed a decreased risk of CRC (P-trend = 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.},
  author       = {Campa, Daniele and Sainz, Juan and Pardini, Barbara and Vodickova, Ludmila and Naccarati, Alessio and Rudolph, Anja and Novotny, Jan and Försti, Asta and Buch, Stephan and von Schoenfels, Witigo and Schafmayer, Clemens and Voelzke, Henry and Hoffmeister, Michael and Frank, Bernd and Barale, Roberto and Hemminki, Kari and Hampe, Jochen and Chang-Claude, Jenny and Brenner, Hermann and Vodicka, Pavel and Canzian, Federico},
  issn         = {1932-6203},
  language     = {eng},
  number       = {3},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {A Comprehensive Investigation on Common Polymorphisms in the MDR1/ABCB1 Transporter Gene and Susceptibility to Colorectal Cancer},
  url          = {http://dx.doi.org/10.1371/journal.pone.0032784},
  volume       = {7},
  year         = {2012},
}