title: Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation.
abstract: The purpose of the present study was to analyze genetic variations in the NBS1 gene and to evaluate the contribution of heterozygous NBS1 mutation to the risk of breast cancer among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation. We screened 235 non-BRCA1/2 Korean patients with high-risk breast cancer for NBS1 mutations. The entire NBS1 gene was sequenced using fluorescent conformation-sensitive capillary electrophoresis. In silico analysis of the NBS1 variants was performed using PolyPhen-2 and SIFT. The frequency of variants predicted to be deleterious by in silico analysis was compared between breast cancer patients and controls. Twenty-eight sequence variants in the NBS1 gene were identified: 9 exonic variants, including 5 missense mutations (p.R169C, p.I171V, p.E185Q, p.E564K, and p.F603L) and 4 silent mutations, and 19 variants within introns. Among the five missense variants, p.I171V (c.511A > G) was the only variant predicted to be deleterious by in silico analysis. Heterozygosity for p.I171V was found in 4/235 patients with breast cancer and 3/281 individuals in the control group. The frequency of p.I171V was not significantly different between the patient and control groups (1.7 vs. 1.06%, p = 0.7). Heterozygosity of p.I171V in the NBS1 gene was found in a small proportion of Korean patients with high-risk breast cancer. The contribution of the p.I171V variant to the development of breast cancer among Korean patients was not significant.
authors.affiliation: Department of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong, South Korea.
authors.forename: Haeyoung
authors.initials: H
authors.lastname: Kim
authors.forename: Dae-Yeon
authors.initials: DY
authors.lastname: Cho
authors.forename: Doo Ho
authors.initials: DH
authors.lastname: Choi
authors.forename: Gee Hue
authors.initials: GH
authors.lastname: Jung
authors.forename: Inkyung
authors.initials: I
authors.lastname: Shin
authors.forename: Won
authors.initials: W
authors.lastname: Park
authors.forename: Seung Jae
authors.initials: SJ
authors.lastname: Huh
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.forename: Sue K
authors.initials: SK
authors.lastname: Park
authors.forename: Jong Won
authors.initials: JW
authors.lastname: Lee
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.forename: Won Ho
authors.initials: WH
authors.lastname: Gil
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D019313:BRCA1 Protein / Q000235:genetics; D024682:BRCA2 Protein / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics*; D018567:Breast Neoplasms, Male / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins