HIGH-FREQUENCY OF P53 GENE-MUTATIONS IN PRIMARY BREAST CANCERS IN JAPANESE WOMEN, A LOW-INCIDENCE POPULATION

The pattern of acquired mutations in the p53 tumour-suppressor gene is potentially useful for determining factors contributing to carcinogen esis in diverse populations differing in incidence and/or mortality fr om the disease. We previously reported differences in mutational patte rns of the p53 gene in primary breast cancers from Midwest US Caucasia n, African-American and Austrian women. Herein, we report 16 mutations in 27 primary breast cancers from Japanese women From Hirosaki, a pop ulation with a low incidence of breast cancer. The frequency of 59.3% of p53 mutations is the highest reported in breast cancers from a part icular ethnic group thus far. A relatively high number of mutations (7 /16) were heterozygous in at least some tumour cell clusters. Intergro up comparisons of the mutational pattern between this population and s everal other US, European and Japanese populations do not show any sta tistically significant differences. There were recurrent mutations at two sites, codon 273 (R-->H; three mutations), a common hotspot of mut ations in breast and other cancers, and codon 183 (S-->Stop; two mutat ions), a very rare location for p53 mutations. These mutations were sh own to be independent and presumably not in the germ line. The highest frequency of p53 mutations raises the possibility that p53 mutagenesi s is a predominant factor for breast cancer development in this low-ri sk Japanese group, whereas in other cohorts different mechanisms are l ikely to account for the higher proportion of breast cancer. Further s tudies are needed to confirm the present observations.