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

Overview

Journal PLoS Genet

Specialty Genetics

Date 2010 Sep 24

PMID 20862326

Citations 49

Authors

Alan M Pittman

Silvia Naranjo

Sanni E Jalava

Philip Twiss

Yussanne Ma

Bianca Olver

Amy Lloyd

Jayaram Vijayakrishnan

Mobshra Qureshi

Peter Broderick

Tom van Wezel

Hans Morreau

Sari Tuupanen

Lauri A Aaltonen

M Eva Alonso

Miguel Manzanares

Angela Gavilan

Tapio Visakorpi

Jose Luis Gomez-Skarmeta

Richard S Houlston

Affiliations

Soon will be listed here.

Abstract

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.

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