title: A comprehensive investigation on common polymorphisms in the MDR1/ABCB1 transporter gene and susceptibility to colorectal cancer.
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.
authors.affiliation: Genomic Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg, Germany.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.forename: Juan
authors.initials: J
authors.lastname: Sainz
authors.forename: Barbara
authors.initials: B
authors.lastname: Pardini
authors.forename: Ludmila
authors.initials: L
authors.lastname: Vodickova
authors.forename: Alessio
authors.initials: A
authors.lastname: Naccarati
authors.forename: Anja
authors.initials: A
authors.lastname: Rudolph
authors.forename: Jan
authors.initials: J
authors.lastname: Novotny
authors.forename: Asta
authors.initials: A
authors.lastname: Försti
authors.forename: Stephan
authors.initials: S
authors.lastname: Buch
authors.forename: Witigo
authors.initials: W
authors.lastname: von Schönfels
authors.forename: Clemens
authors.initials: C
authors.lastname: Schafmayer
authors.forename: Henry
authors.initials: H
authors.lastname: Völzke
authors.forename: Michael
authors.initials: M
authors.lastname: Hoffmeister
authors.forename: Bernd
authors.initials: B
authors.lastname: Frank
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.forename: Kari
authors.initials: K
authors.lastname: Hemminki
authors.forename: Jochen
authors.initials: J
authors.lastname: Hampe
authors.forename: Jenny
authors.initials: J
authors.lastname: Chang-Claude
authors.forename: Hermann
authors.initials: H
authors.lastname: Brenner
authors.forename: Pavel
authors.initials: P
authors.lastname: Vodicka
authors.forename: Federico
authors.initials: F
authors.lastname: Canzian
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics*; D018153:Czech Republic; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D012306:Risk
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1