Low Frequency of p53 Gene Mutations in Breast Cancers of Japanese-American Women

Differences in frequencies and patterns of somatic p53 gene mutations among racially and geographically diverse populations presumably reflect exposure to different mutagens or different responses to certain mutagens. On emigration to the United States, Japanese women experience, over several generations, a four- to fivefold increase in the incidence of breast cancer. To determine whether this increased incidence is associated with a change in the frequency and/or type of p53 mutation in their tumors, we examined paraffin-embedded samples of primary breast cancers from Japanese-American women in Los Angeles County, CA. Mutations in exons 5-9 and adjacent intronic regions of the p53 gene were identified and confirmed by direct sequencing. Seven mutations, including 5 missense, were detected in 44 primary breast carcinomas, a frequency of 16%. There were six transitions and one transversion. As expected, overexpression of p53 protein, detected by immunohistochemistry, occurred in tumors with missense mutations; tumors with nonsense or splice junction mutations had no detectable p53 protein. The frequency of p53 gene mutations showed no increase over that previously found in breast cancers of native Japanese women. The increased incidence of breast cancer in Japanese-American women is likely to be multifactorial in nature and warrants further studies.