1. Heterozygous germline mutations in NBS1 among Korean patients with high-risk breast cancer negative for BRCA1/2 mutation
- Author
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Seung Jae Huh, Seok Won Kim, Dae Yeon Cho, Won Park, Jong Won Lee, Gee Hue Jung, Doo Ho Choi, Seok Jin Nam, Sung Won Kim, Won Ho Gil, Inkyung Shin, Haeyoung Kim, Jeong Eon Lee, and Sue K. Park
- Subjects
Adult ,Male ,Silent mutation ,Heterozygote ,Cancer Research ,In silico ,Mutation, Missense ,Breast Neoplasms ,Cell Cycle Proteins ,Biology ,medicine.disease_cause ,Breast Neoplasms, Male ,Loss of heterozygosity ,Germline mutation ,Breast cancer ,Asian People ,Gene Frequency ,Genetic variation ,Genetics ,medicine ,Humans ,Missense mutation ,Genetic Predisposition to Disease ,Germ-Line Mutation ,Genetics (clinical) ,BRCA2 Protein ,Mutation ,BRCA1 Protein ,Nuclear Proteins ,medicine.disease ,Oncology ,Case-Control Studies ,Female - 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.
- Published
- 2015