title: Functional NBS1 polymorphism is associated with occurrence and advanced disease status of nasopharyngeal carcinoma.
abstract: As a component of the MRN (MRE11/RAD50/NBS1) complex, NBS1 plays an important role in cellular response to DNA damage and the maintenance of chromosomal integrity. The NBS1 E185Q polymorphism (8360G>C, rs1805794) has been frequently studied in some cancers with discordant results, but its association with nasopharyngeal carcinoma (NPC) in Chinese population has not been investigated. Moreover, there is no report about the association between NBS1 3'UTR variant rs2735383 and the risk of NPC. A multiple center case-control analysis was performed to assess the association between NBS1 polymorphisms and NPC risk in Eastern and Southern Chinese population. The genotypes and haplotypes were determined in 1052 cases and 1168 controls and the associations with risk of NPC were estimated by logistic regression. Cell migration assays were performed in 24-well transwell chambers to detect the effects of NBS1 E185Q SNP on cell migration. We observed significant difference in genotype frequencies at the rs1805794 C/G site between cases and controls (P(trend) < 0.0001). The C allele increases the risk for invasive disease or metastatic disease, compared with G allele. More over, CNE-2 cells (NPC cell line) transfected with pcDNA-NBS1-185Q (8360CC) had significantly higher migration levels than those transfected with pcDNA-NBS1-185E (8360GG) (P = 0.024). These findings suggest that E185Q polymorphism in NBS1 may be a genetic modifier for the occurrence and aggression of NPC.
authors.affiliation: Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Chun
authors.initials: C
authors.lastname: Zhang
authors.forename: Lan
authors.initials: L
authors.lastname: Jiang
authors.forename: Yonghe
authors.initials: Y
authors.lastname: You
authors.forename: Yuehui
authors.initials: Y
authors.lastname: Liu
authors.forename: Jiachun
authors.initials: J
authors.lastname: Lu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics*; D002460:Cell Line; D017931:DNA Primers; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D020413:3' Untranslated Regions; D018797:Cell Cycle Proteins; D017931:DNA Primers; C112156:NBN protein, human; D009687:Nuclear Proteins