title: Functional Genetic Variations at the microRNA Binding-Site in the CD44 Gene Are Associated with Risk of Colorectal Cancer in Chinese Populations.
abstract: CD44 as one of the most putative stem cell markers plays a key role in many cellular processes, including cancer cell growth and migration. Functional single nucleotide polymorphisms (SNPs) of CD44 may modulate its gene functions and thus cancer risk. In the current study, we investigated if polymorphisms in the 3'-untranslated region (UTR) of CD44 are associated with increased susceptibility to colorectal cancer (CRC) by conducting a case-control study of 946 CRC patients and 989 cancer-free controls. Three polymorphisms (rs13347C/T, rs10836347C/T, rs11821102G/A) in the 3'-UTR of CD44 were genotyped. We found that the variant genotypes (CT and TT) of rs13347 (adjusted odds ratio (OR)=1.79, 95% confidence interval (CI)=1.50-2.17) increased an individual's susceptibility to CRC, compared with rs13347CC homozygous genotypes. We also found that CRC patients with the CT/TT genotype had a 1.6-fold increased risk for developing advanced (stage III + IV) CRC. Furthermore, functional assays showed that the C to T base change at rs13347C/T disrupts the binding site for the microRNA hsa-mir-509-3p, thereby increasing CD44 transcriptional activity and expression level. These findings suggest that the rs13347C/T in microRNA binding site may be potential biomarkers for genetic susceptibility to CRC.
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Haining Branch of Zhejiang Provincial People's Hospital, Jiaxing, Zhejiang Province, People's Republic of China.
authors.forename: Hong-Guo
authors.initials: HG
authors.lastname: Yang
authors.affiliation: Department of Colo-Rectal Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Bo-An
authors.initials: BA
authors.lastname: Zheng
authors.affiliation: Department of Colo-Rectal Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Hong-Feng
authors.initials: HF
authors.lastname: Cao
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Hu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang Province, People's Republic of China.
authors.forename: Wei-Ding
authors.initials: WD
authors.lastname: Wu
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D015179:Colorectal Neoplasms / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide
chemical_list: D018960:Hyaluronan Receptors; C571982:MIRN509 microRNA, human; D035683:MicroRNAs