A genetic variant in the promoter region of miR-34b/c is associated with a reduced risk of colorectal cancer

The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs -mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-...

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Published inBiological chemistry Vol. 394; no. 3; pp. 415 - 420
Main Authors Gao, Lin-Bo, Li, Li-Juan, Pan, Xin-Min, Li, Zhao-Hui, Liang, Wei-Bo, Bai, Peng, Zhu, Yin-Hua, Zhang, Lin
Format Journal Article
LanguageEnglish
Published Germany De Gruyter 01.03.2013
Subjects
colorectal cancer
Colorectal Neoplasms - genetics
Colorectal Neoplasms - physiopathology
Female
Genetic Predisposition to Disease
Genetic Variation
Humans
Male
MicroRNAs - genetics
miR-34b/c
polymorphism
Polymorphism, Single Nucleotide
Promoter Regions, Genetic - genetics
TP53
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Summary:The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs -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 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 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.
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ISSN:1431-6730
1437-4315
DOI:10.1515/hsz-2012-0297