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

作者：Pittman Alan M^*; Naranjo Silvia; Jalava Sanni E; Twiss Philip; Ma Yussanne; Olver Bianca; Lloyd Amy; Vijayakrishnan Jayaram; Qureshi Mobshra; Broderick Peter; van Wezel Tom; Morreau Hans; Tuupanen Sari; Aaltonen Lauri A; Eva Alonso M; Manzanares Miguel; Gavilan Angela; Visakorpi Tapio; Luis Gomez Skarmeta Jose; Houlston Richard S

来源：PLoS Genetics, 2010, 6(9): e1001126.

DOI：10.1371/journal.pgen.1001126

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.

• 出版日期2010-9
• 单位河北医科大学