title: Associations between NBS1 Polymorphisms and Colorectal Cancer in Chinese Population.
abstract: As the central protein of the double strand breaks (DSB)-induced DNA repair pathway, NBS1 participates in detecting the DSBs and plays an essential role in maintaining genomic stability. Single nucleotide polymorphisms (SNPs) in NBS1 gene were commonly tested that associated with the susceptibility to multiple cancers, but the results remained controversial. Thus, we conducted two independent hospital-based case-control studies comprising 1,072 colorectal cancer patients and 1,263 controls to evaluate the association between four NBS1 SNPs and colorectal cancer risk. The result showed that rs2735383C/G polymorphism in the 3'-untranslated region (UTR) of NBS1 was significantly associated with risk of colorectal cancer using logistic regression (P<10(-4)). Furthermore, we observed that rs2735383CC genotype was associated with substantially increased risk of colorectal cancer (odds ratio=1.55, 95% confidence interval=1.27-1.94), compared with the rs2735383GC+GG genotypes. Further functional experiments demonstrated that the rs2735383C allele in the NBS1 disrupted the binding affinity of has-miR-509-5p to the NBS1 3'-UTR in colorectal cancer cells, affecting the NBS1 transcriptional activity and expression level. In conclusion, current evidence suggests that the rs2735383C/G polymorphism might contribute to the risk for colorectal cancer.
authors.affiliation: Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Jing-Tao
authors.initials: JT
authors.lastname: Li
authors.affiliation: Department of general surgery, First Affiliated Hospital of Gannan Medical College, Ganzhou, China.
authors.forename: Bao-Yuan
authors.initials: BY
authors.lastname: Zhong
authors.affiliation: Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Hui-Hui
authors.initials: HH
authors.lastname: Xu
authors.affiliation: Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Sheng-Yan
authors.initials: SY
authors.lastname: Qiao
authors.affiliation: Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Wang
authors.affiliation: Institute of Clinical Medicine, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, The People's Hospital of Yichun City, Yichun, China.
authors.forename: Hui-Zhen
authors.initials: HZ
authors.lastname: Fan
authors.affiliation: Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, China.
authors.forename: Hong-Chuan
authors.initials: HC
authors.lastname: Zhao
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012307:Risk Factors; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D012333:RNA, Messenger; D008156:Luciferases