NOVEL PATTERN OF P53 MUTATION IN BREAST CANCERS FROM AUSTRIAN WOMEN

Since mutagens produce an extraordinary diversity of mutational patter ns, differential mutational exposures among populations are expected t o produce different patterns of mutation. Classical epidemiological me thods have been successful in implicating specific mutagens in cancers such as those of lung and skin in which one mutagen predominates. In breast cancer, however, no mutagens have been implicated in an unequiv ocal manner. In an attempt to facilitate epidemiological studies, we h ave been studying the pattern of p53 gene mutations in breast cancers from multiple populations with high and low breast cancer incidences. We previously reported that breast cancers from Midwest United States, predominantly rural Caucasian women, have a different pattern of p53 gene mutation from populations of Western European women. Herein, we a nalyze patterns of p53 mutations from Graz, Austria, another populatio n with a high incidence of breast cancer. Among the 60 Austrian breast cancers analyzed, 14 (23 %) have a p53 gene mutation in exons 5-9 or in adjacent splice junctions. Analysis of the patterns of mutation sho ws differences between the ''Western European'' profile and the Austri an and Midwest United States groups (P = 0.027 and 0.024, respectively ). The Austrian pattern is characterized by a high frequency of A:T--> T:A transversions (P = 0.006). The presence of distinct patterns of mu tation among the limited number of analyzed populations of Western Eur opean origin supports the idea that differential mutagenic exposure an d/or genetic differences contribute to breast cancer mutagenesis among geographically distinct Caucasians of Western European origin.