title: 3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.
abstract: MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and XPO5 rs11077 AA genotype (CT/AA) carriers experienced reduced CRC susceptibility (both colon and rectal). Subgroup analysis demonstrated that the combined RAN rs14035 CT + TT genotype was associated with rectal cancer, but not colon cancer. In addition, the DICER1 rs3742330 AG genotype was associated with a significantly increased risk of colon cancer. Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer. In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate. Furthermore, patients diagnosed with hypertension or DM who carried the DROSHA rs10719 CC genotype showed increased CRC risk, while the XPO5 rs11077 AC+CC genotype led to increased CRC risk in patients with hypertension only. Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.
authors.forename: Jung Jae
authors.initials: JJ
authors.lastname: Ko
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Jung Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Jeon
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea.
authors.forename: Jung Ki
authors.initials: JK
authors.lastname: Yoo
authors.affiliation: Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Jisu
authors.initials: J
authors.lastname: Oh
authors.affiliation: Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea; Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Doyeun
authors.initials: D
authors.lastname: Oh
authors.affiliation: Department of Surgery, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Jong Woo
authors.initials: JW
authors.lastname: Kim
authors.affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.
authors.forename: Nam Keun
authors.initials: NK
authors.lastname: Kim
mesh_terms: D020413:3' Untranslated Regions; D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D015179:Colorectal Neoplasms / Q000235:genetics*; D053487:DEAD-box RNA Helicases / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006710:Homocysteine / Q000378:metabolism; D006801:Humans; D028884:Karyopherins / Q000235:genetics*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012334:RNA, Neoplasm / Q000378:metabolism*; D056910:Republic of Korea / Q000453:epidemiology; D043244:Ribonuclease III / Q000235:genetics*; D012306:Risk; D047368:Tumor Burden; D020931:ran GTP-Binding Protein / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D028884:Karyopherins; D035683:MicroRNAs; C120587:RAN protein, human; D012334:RNA, Neoplasm; C446511:XPO5 protein, human; D006710:Homocysteine; D005492:Folic Acid; C408087:DICER1 protein, human; C517918:DROSHA protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D020931:ran GTP-Binding Protein