title: Polymorphisms of the pri-miR-34b/c promoter and TP53 codon 72 are associated with risk of colorectal cancer.
abstract: The microRNA (miR)-34 family is a direct transcriptional target of tumor-suppressor TP53 and loss of miR-34 function may impair TP53-mediated cell cycle arrest and apoptosis. In the present study, we investigated whether the single nucleotide polymorphisms (SNPs) rs4938723 (T>C) in the promoter region of miR-34b/c and Arg72Pro (G>C) in codon 72 of TP53 are independently or complementarily associated with the risks and clinical outcomes of colorectal cancer (CRC) and whether the combined effect of these SNPs and metabolic risk factors are related to CRC. We evaluated the SNPs in 545 CRC patients and 428 healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequence analysis. We found that the GC and GC/CC genotypes of TP53 Arg72Pro were associated with decreased risk of CRC (adjusted OR = 0.727 for GC; OR = 0.735 for GC/CC). The combined genotypes of TT-GC and CC-GG were significantly associated with reduced CRC risk (adjusted OR = 0.628 for TT-GC; OR = 0.381 for CC-GG, respectively). The SNP rs4938723 and diabetes mellitus (DM) together were associated with an increased CRC risk, but the SNP TP53 Arg72Pro CC with DM showed a protective effect against CRC. These findings indicate that rs4938723 in the promoter region of pri-miR-34b/c and the SNP in TP53 codon 72 were related to decreased risk of CRC in the population studied and those metabolic diseases and genetic variants influence each other with regard to CRC susceptibility.
authors: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Jisu
authors: J
authors: Oh
authors: Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Jong Woo
authors: JW
authors: Kim
authors: Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Bo Eun
authors: BE
authors: Lee
authors: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Moon Ju
authors: MJ
authors: Jang
authors: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: So Young
authors: SY
authors: Chong
authors: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Pil Won
authors: PW
authors: Park
authors: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Seong Gyu
authors: SG
authors: Hwang
authors: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Doyeun
authors: D
authors: Oh
authors: Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
authors: Nam Keun
authors: NK
authors: Kim
mesh_terms: D017209:Apoptosis / Q000235:genetics; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D056910:Republic of Korea; D012189:Retrospective Studies; D012306:Risk; D017422:Sequence Analysis, DNA; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53