title: RAD50 and NBS1 are not likely to be susceptibility genes in Chinese non-BRCA1/2 hereditary breast cancer.
abstract: Deleterious mutations in several genes that are involved in repair of damage to DNA have been associated with an increased risk of breast cancer. Recent studies have shown sequence variants in two such genes, RAD50 and NBS1, which can be predisposed to breast cancer. The aim of this study is to elucidate the contribution of RAD50 and NBS1 germline mutations to the etiology of non-BRCA1/2 hereditary breast cancer in China. We conducted a mutational analysis of RAD50 and NBS1 in genomic DNA from 384 Chinese women with early-onset breast cancer and/or affected relatives. All the coding exons and adjacent intronic splice junction rejoins of RAD50 and NBS1 were screened using PCR-DHPLC and DNA sequencing analysis. Among all cases, no obviously deleterious mutations were observed in RAD50; one synonymous change c.102G>A at codon 34 and one single nucleotide polymorphism IVS9 + 19C>T were identified in NBS1. Furthermore, there was no remarkable difference in the allele frequency of NBS1 c.553G>C (E185Q) between cases (172/384) and controls (182/420). Our results exclude the possible role of RAD50 and NBS1 in familial breast cancer predisposition in Chinese women, and there is no evidence for the recommendation of RAD50 and NBS1 for genetic testing in China.
authors.affiliation: Breast Cancer Institute, Cancer Hospital/Cancer Institute, Shanghai Medical College, Institutes of Biomedical Science, Fudan University, 270 Dong'an Road, Shanghai 200032, People's Republic of China.
authors.forename: Min
authors.initials: M
authors.lastname: He
authors.forename: Gen-Hong
authors.initials: GH
authors.lastname: Di
authors.forename: A-Yong
authors.initials: AY
authors.lastname: Cao
authors.forename: Zhen
authors.initials: Z
authors.lastname: Hu
authors.forename: Wei
authors.initials: W
authors.lastname: Jin
authors.forename: Zhen-Zhou
authors.initials: ZZ
authors.lastname: Shen
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Shao
mesh_terms: D017766:Acid Anhydride Hydrolases; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D002681:China; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation; D006801:Humans; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; D045643:DNA Repair Enzymes