Abnormal FHIT transcripts in human breast carcinomas: A clinicopathological and epidemiological analysis of 61 Japanese cases

Deletions in the short arm of chromosome 3 have been found in various human cancers, including breast cancer. Recently, the FHIT (fragile histidine triad) gene was identified at 3p14.2 as a candidate tumor suppressor gene. We examined the abnormal transcripts of the FHIT gene in 61 Japanese primary breast cancer specimens and found that 23 (38%) of them exhibited abnormalities, about half of which were categorized into two types of aberrant transcripts. Sequence analysis of these aberrant transcripts revealed the absence of exons 5-7 (type I) and exons 5-8 (type II). Clinicopathological and epidemiological analysis of patients showed that the abnormal FHIT transcripts were not associated with age, tumor-node-metastasis classification, tumor size, estrogen receptor and progesterone receptor status, local metastasis, family history of breast cancer, or lifestyle factors of patients, including cigarette smoking and alcohol consumption. On the other hand, we found that the abnormal transcripts of type I and type II were associated with the incidence of bilateral breast cancer and that decreased frequency of childbirth was also associated with FHIT abnormalities.