title: Germline mutations 657del5 of the NBS1 gene contribute significantly to the incidence of breast cancer in Central Poland.
abstract: Recent studies have demonstrated that heterozygous carriers of the NBS1 657del5 mutation have an increased risk for familial and bilateral breast cancer, but similar studies in consecutive breast cancer patients were inconclusive. Here, in a study of 562 nonselected breast cancer patients from Central Poland, we found 11 (1.96%) 657del5 mutation carriers vs. 3.47 expected (OR 3.21, 95%CI: 1.36-7.61, p = 0.0107) and only 9 (1.6%) carriers of the 5382insC mutation of the BRCA1 gene, most frequently found among breast cancer patients in Poland. No carriers of R215W, another pathogenic mutation of the NBS1 gene, were found in the present study. All carriers of the 657del5 mutation had sporadic breast tumors while 5 of 9 5382insC carriers had a family history of breast/ovarian cancer or bilateral breast carcinoma. In the pooled group of patients from the present and our previous study, carried out also in patients from Central Poland, we obtained the following risk estimates (OR) for 657del5 carriers, as related to the age at breast cancer diagnosis: < 40 years: 8.36; (95%CI: 2.57-27.27) p = 0.0003; < 50 years: 4.27 (95%CI: 1.67-10.89) p = 0.003; > or = 50 years: 2.40 (95%CI: 0.91-6.35) p = 0.1250; all ages: 3.13 (95% CI: 1.40-7.00) p = 0.0066. These findings demonstrate conclusively that NBS1 657del5 mutation carriers have a significantly, though moderately increased, age-related risk of breast cancer, and imply that in populations with a high 657del5 carrier frequency this mutation may contribute substantially to the overall incidence of breast cancer, particularly in younger age groups.
authors.affiliation: Department of Immunology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland. jsteffen@coi.waw.pl
authors.forename: Jan
authors.initials: J
authors.lastname: Steffen
authors.forename: Dorota
authors.initials: D
authors.lastname: Nowakowska
authors.forename: Anna
authors.initials: A
authors.lastname: Niwińska
authors.forename: Dorota
authors.initials: D
authors.lastname: Czapczak
authors.forename: Anna
authors.initials: A
authors.lastname: Kluska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Piatkowska
authors.forename: Alicja
authors.initials: A
authors.lastname: Wiśniewska
authors.forename: Zygmut
authors.initials: Z
authors.lastname: Paszko
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006579:Heterozygote; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D011044:Poland / Q000453:epidemiology; D012307:Risk Factors
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins