title: Molecular epidemiology of breast cancers in northern and southern Japan: the frequency, clustering, and patterns of p53 gene mutations differ among these two low-risk populations.
abstract: Comparison of acquired mutations in the p53 tumor suppressor gene can illuminate factors contributing to carcinogenesis among cancer cohorts. Japan has an ethnically homogeneous population with a low incidence of breast cancer. Previously we reported an unusual frequency, allelic status, and clustering of mutations in breast cancers from the northern part of the main Japanese island. To extend these findings, exons 2-11 and adjacent intronic sequences were analysed in tumors of women from northern (Hokkaido) and southern (Tokushima) Japan. The frequency of breast cancers with p53 gene mutations in the Hokkaido group is the highest reported (81%) while that in Tokushima (28%) is similar to most other populations. Thirteen of the 19 mutations (68.4%) in the Hokkaido cohort were heterozygous, an unusually high frequency for p53 mutations in any tumor type. There were three missense mutations at codon 175, a known hotspot for alterations in the p53 gene, and three missense mutations at codon 179, a rare site for p53 changes. In addition, the patterns of p53 gene mutation differed between the two Japanese cohorts (P=0.04). The multiple differences in acquired p53 mutations suggest unsuspected biological differences among breast cancers in northern and southern Japan. In addition, the high frequency of p53 mutations in breast cancers from Hokkaido predicted a poorer prognosis for this population which was confirmed on examination of mortality data.
authors.affiliation: Department of Oncology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
authors.forename: H
authors.initials: H
authors.lastname: Blaszyk
authors.forename: A
authors.initials: A
authors.lastname: Hartmann
authors.forename: Y
authors.initials: Y
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Saitoh
authors.forename: J M
authors.initials: JM
authors.lastname: Cunningham
authors.forename: R M
authors.initials: RM
authors.lastname: McGovern
authors.forename: J J
authors.initials: JJ
authors.lastname: Schroeder
authors.forename: D J
authors.initials: DJ
authors.lastname: Schaid
authors.forename: K
authors.initials: K
authors.lastname: Ii
authors.forename: Y
authors.initials: Y
authors.lastname: Monden
authors.forename: T
authors.initials: T
authors.lastname: Morimoto
authors.forename: K
authors.initials: K
authors.lastname: Komaki
authors.forename: M
authors.initials: M
authors.lastname: Sasa
authors.forename: K
authors.initials: K
authors.lastname: Hirata
authors.forename: M
authors.initials: M
authors.lastname: Okazaki
authors.forename: J S
authors.initials: JS
authors.lastname: Kovach
authors.forename: S S
authors.initials: SS
authors.lastname: Sommer
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D016158:Genes, p53 / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology / Q000208:ethnology; D008875:Middle Aged; D017354:Point Mutation / Q000235:genetics*; D013029:Space-Time Clustering; D019371:Topography, Medical