[Loss of exons of FHIT gene and FHIT protein expression in Yunnan tin miners with lung cancer].

BACKGROUND & OBJECTIVE: Yunnan tin miners have an extremely high incidence of lung cancer. Abnormality of the fragile histidine triad (FHIT) gene has been proved to closely relate to lung cancer development. This study was to explore the loss of exons 3, 4, 5 and 8 of FHIT gene and FHIT protein expression in Yunnan Tin miners with lung cancer. METHODS: The exons 3, 4, 5, and 8 of FHIT gene in lung cancer cell line YTMCC of a Yunnan Tin miner, and 30 specimens of lung cancer from Yunnan Tin miners in Gejiu district and 22 specimens of lung cancer from non-miners in other regions were detected by polymerase chain reaction (PCR). The expression of FHIT protein in 90 specimens of human lung cancer and 43 specimens of lung cancer developed by the intratracheal instillation of Yunnan Tin mineral dust in F344 rats was detected by immunohistochemistry. RESULTS: Losses of exon 3 and exon 8 were detected in YTMCC cells. Lung cancer samples from Yunnan Tin miners and non-miners exhibited heterozygous loss of FHIT gene among exons 3, 4, 5 and 8. The percentages of FHIT gene deletion and loss of FHIT protein expression in Yunnan Tin miners with lung cancer were 68.2% and 70.6%, respectively. The percentages of FHIT gene heterozygous loss was significantly higher in lung cancer tissue than in normal lung tissue (P < 0.01). Loss of FHIT protein expression was detected in the early stage of F344 rat lung canceration after treatment of Yunnan tin Mineral dust:the percentage was 100% in 8 specimens of squamous dysplasia, carcinoma in situ, and early stage of squamous cell carcinoma. CONCLUSIONS: Deletion and abnormal expression of FHIT gene are common in Yunnan tin miners and non-miners with lung cancer. The high rate of loss of FHIT expression in precancerous lesions and lung cancer at early stage indicates that FHIT could be an early screening target of lung cancer.