Allelic Variation at the 8q23.3 Colorectal Cancer Risk Locus Functions as a Cis-Acting Regulator of EIF3H

被引：69

作者：

Pittman, Alan M. ^{[1
]}

Naranjo, Silvia ^{[2
]}

Jalava, Sanni E. ^{[3
,4
]}

Twiss, Philip ^{[1
]}

Ma, Yussanne ^{[1
]}

Olver, Bianca ^{[1
]}

Lloyd, Amy ^{[1
]}

Vijayakrishnan, Jayaram ^{[1
]}

Qureshi, Mobshra ^{[1
]}

Broderick, Peter ^{[1
]}

van Wezel, Tom ^{[5
]}

Morreau, Hans ^{[5
]}

Tuupanen, Sari ^{[6
]}

Aaltonen, Lauri A. ^{[6
]}

Eva Alonso, M. ^{[7
]}

Manzanares, Miguel ^{[7
]}

Gavilan, Angela ^{[8
]}

Visakorpi, Tapio ^{[3
,4
]}

Luis Gomez-Skarmeta, Jose ^{[2
]}

Houlston, Richard S. ^{[1
]}

机构：

[1] Inst Canc Res, Sect Canc Genet, Sutton, Surrey, England

[2] CSIC UPO, Ctr Andaluz Biol Desarrollo, Seville, Spain

[3] Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland

[4] Tampere Univ Hosp, Tampere, Finland

[5] Leiden Univ, Dept Pathol, Med Ctr, Leiden, Netherlands

[6] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[7] Ctr Nacl Invest Cardiovasc, Madrid, Spain

[8] Univ Pablo Olavide CSIC, Ctr Nacl Invest Biomed Red Enfermedades Raras CIB, Seville, Spain

来源：

PLOS GENETICS | 2010年 / 6卷 / 09期

基金：

芬兰科学院;

关键词：

GENOME-WIDE ASSOCIATION; GENE-EXPRESSION PROFILES; SUSCEPTIBILITY LOCI; PROSTATE-CANCER; CHROMOSOME; 8Q24; RS6983267; VARIANT; SCAN; PREDISPOSITION; TRANSGENESIS;

D O I：

10.1371/journal.pgen.1001126

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Common genetic variation at human 8q23.3 is significantly associated with colorectal cancer (CRC) risk. To elucidate the basis of this association we compared the frequency of common variants at 8q23.3 in 1,964 CRC cases and 2,081 healthy controls. Reporter gene studies showed that the single nucleotide polymorphism rs16888589 acts as an allele-specific transcriptional repressor. Chromosome conformation capture (3C) analysis demonstrated that the genomic region harboring rs16888589 interacts with the promoter of gene for eukaryotic translation initiation factor 3, subunit H (EIF3H). We show that increased expression of EIF3H gene increases CRC growth and invasiveness thereby providing a biological mechanism for the 8q23.3 association. These data provide evidence for a functional basis for the non-coding risk variant rs16888589 at 8q23.3 and provides novel insight into the etiological basis of CRC.

引用

页数：9

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