title: Role of the Nijmegen breakage syndrome 1 gene in familial and sporadic prostate cancer.
abstract: The Nijmegen breakage syndrome 1 (NBS1) gene, which participates in DNA double strand break repair, has been postulated to be a susceptibility factor for a number of cancers, including prostate cancer. Numerous mutations have been identified in NBS1, including the founder mutation 657del5. In this study, a number of analyses were done to determine whether mutations in NBS1 are associated with an increased risk for prostate cancer. The frequency of the 657del5 mutation in both familial prostate cancer cases (1,819 affected men among 909 families) and sporadic prostate cancer cases (1,218 affected men) collected from five centers participating in the International Consortium for Prostate Cancer Genetics were compared with that found in 697 normal controls. Seven individuals were identified to carry the mutation among the 3,037 cases screened: four in the familial group (three from one family and one from another) and three in the sporadic cases. The carrier frequency was 0.22% (2 of 909) for the probands and 0.25% (3 of 1,218) for the sporadic cases of prostate cancer. The 657del5 mutation was not detected in either the 293 unaffected members of the prostate cancer families or in the 697 control samples tested. The entire NBS1 gene was also sequenced in 20 of the youngest affected individuals from the Finnish group of familial cases to identify the presence of possible mutations in this high-risk group. One rare (D95N) and one common (E185Q) missense alteration was identified. More detailed analyses of the E185Q polymorphism, along with a third rare variant (R215W), failed to show an association with prostate cancer. Because the 657del5 mutation was absent from the control population, we are unable to determine if this alteration predisposes to prostate cancer. However, our data does suggest that mutations within NBS1, and in particular, 657del5, do not significantly contribute to the overall prostate cancer burden within our patient samples.
authors.affiliation: Mayo Clinic Rochester, 200 First Street Southwest, 920 Hilton Building, Rochester, MN 55905, USA.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Hebbring
authors.forename: Henna
authors.initials: H
authors.lastname: Fredriksson
authors.forename: Kirsten A
authors.initials: KA
authors.lastname: White
authors.forename: Christiane
authors.initials: C
authors.lastname: Maier
authors.forename: Charles
authors.initials: C
authors.lastname: Ewing
authors.forename: Shannon K
authors.initials: SK
authors.lastname: McDonnell
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Jacobsen
authors.forename: James
authors.initials: J
authors.lastname: Cerhan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: Tarja
authors.initials: T
authors.lastname: Ikonen
authors.forename: Ville
authors.initials: V
authors.lastname: Autio
authors.forename: Teuvo L J
authors.initials: TL
authors.lastname: Tammela
authors.forename: Kathleen
authors.initials: K
authors.lastname: Herkommer
authors.forename: Thomas
authors.initials: T
authors.lastname: Paiss
authors.forename: Walther
authors.initials: W
authors.lastname: Vogel
authors.forename: Marta
authors.initials: M
authors.lastname: Gielzak
authors.forename: Jurga
authors.initials: J
authors.lastname: Sauvageot
authors.forename: Johanna
authors.initials: J
authors.lastname: Schleutker
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Cooney
authors.forename: William
authors.initials: W
authors.lastname: Isaacs
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049932:Nijmegen Breakage Syndrome / Q000453:epidemiology / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D018797:Cell Cycle Proteins; C112156:NBN protein, human; D009687:Nuclear Proteins