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...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/443aefca63314deba20672112c67cdda |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:443aefca63314deba20672112c67cdda |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:443aefca63314deba20672112c67cdda2021-11-18T07:26:13ZA comprehensive investigation on common polymorphisms in the MDR1/ABCB1 transporter gene and susceptibility to colorectal cancer.1932-620310.1371/journal.pone.0032784https://doaj.org/article/443aefca63314deba20672112c67cdda2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22396794/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203ATP 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.Daniele CampaJuan SainzBarbara PardiniLudmila VodickovaAlessio NaccaratiAnja RudolphJan NovotnyAsta FörstiStephan BuchWitigo von SchönfelsClemens SchafmayerHenry VölzkeMichael HoffmeisterBernd FrankRoberto BaraleKari HemminkiJochen HampeJenny Chang-ClaudeHermann BrennerPavel VodickaFederico CanzianPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e32784 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Daniele Campa Juan Sainz Barbara Pardini Ludmila Vodickova Alessio Naccarati Anja Rudolph Jan Novotny Asta Försti Stephan Buch Witigo von Schönfels Clemens Schafmayer Henry Völzke Michael Hoffmeister Bernd Frank Roberto Barale Kari Hemminki Jochen Hampe Jenny Chang-Claude Hermann Brenner Pavel Vodicka Federico Canzian A 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 (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. |
| format |
article |
| author |
Daniele Campa Juan Sainz Barbara Pardini Ludmila Vodickova Alessio Naccarati Anja Rudolph Jan Novotny Asta Försti Stephan Buch Witigo von Schönfels Clemens Schafmayer Henry Völzke Michael Hoffmeister Bernd Frank Roberto Barale Kari Hemminki Jochen Hampe Jenny Chang-Claude Hermann Brenner Pavel Vodicka Federico Canzian |
| author_facet |
Daniele Campa Juan Sainz Barbara Pardini Ludmila Vodickova Alessio Naccarati Anja Rudolph Jan Novotny Asta Försti Stephan Buch Witigo von Schönfels Clemens Schafmayer Henry Völzke Michael Hoffmeister Bernd Frank Roberto Barale Kari Hemminki Jochen Hampe Jenny Chang-Claude Hermann Brenner Pavel Vodicka Federico Canzian |
| author_sort |
Daniele Campa |
| 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. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/443aefca63314deba20672112c67cdda |
| work_keys_str_mv |
AT danielecampa acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT juansainz acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT barbarapardini acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT ludmilavodickova acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT alessionaccarati acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT anjarudolph acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT jannovotny acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT astaforsti acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT stephanbuch acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT witigovonschonfels acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT clemensschafmayer acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT henryvolzke acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT michaelhoffmeister acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT berndfrank acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT robertobarale acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT karihemminki acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT jochenhampe acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT jennychangclaude acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT hermannbrenner acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT pavelvodicka acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT federicocanzian acomprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT danielecampa comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT juansainz comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT barbarapardini comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT ludmilavodickova comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT alessionaccarati comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT anjarudolph comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT jannovotny comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT astaforsti comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT stephanbuch comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT witigovonschonfels comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT clemensschafmayer comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT henryvolzke comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT michaelhoffmeister comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT berndfrank comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT robertobarale comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT karihemminki comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT jochenhampe comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT jennychangclaude comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT hermannbrenner comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT pavelvodicka comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer AT federicocanzian comprehensiveinvestigationoncommonpolymorphismsinthemdr1abcb1transportergeneandsusceptibilitytocolorectalcancer |
| _version_ |
1718423469657423872 |