title: A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer.
abstract: The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34-0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64-0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43-0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.
authors.affiliation: Laboratory of Molecular and Translational Medicine, West China Institute of Women and Children's Health, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Lin-Bo
authors.initials: LB
authors.lastname: Gao
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Li
authors.forename: Xin-Min
authors.initials: XM
authors.lastname: Pan
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Li
authors.forename: Wei-Bo
authors.initials: WB
authors.lastname: Liang
authors.forename: Peng
authors.initials: P
authors.lastname: Bai
authors.forename: Yin-Hua
authors.initials: YH
authors.lastname: Zhu
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
mesh_terms: D015179:Colorectal Neoplasms / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs