| Summary: | 碩士 === 高雄醫學大學 === 醫學研究所 === 91 === Abstract
The prevalence of betel quid chewing habit has been increasing in Taiwan area, and there were reports concerning about the relationships between betel quid and cancers, either in animal model or human, stated that betel quid was a potent carcinogens. It can lead to tongue cancer, oral cancer, esophageal cancer and even hepatoma, lung cancer & gastric cancer. Betel chewing enjoys island-wide popularity among the inhabitants of Taiwan; the number of current and ex-user was estimated at a 2.0 million people. However, there is no conclusion about the carcinogenesis of esophageal cancer, how the betel quid influence the carcinogenesis and what the role P16 and Rb tumor suppressor gene & telomerase are.
P16 gene and RB gene are tumor suppressor genes and studied in many cancers. The cyclin-dependent kinase inhibitor p16 gene, mapped on chromosome 9p21, is presumed to be the tumor-suppressor gene and that helps to stop transition from the late G1 to the S phase of the cell cycle. Rb gene is mapped on chromosome 13q14. Transition from the preproliferative G1 to the proliferative S phase of the cell cycle is regulated by phosphorylation of the retinoblastoma (Rb) protein.
Recently, telomeric length of chromosome ends has been implicated in the control of cellular immortality and aging. Telomeric DNA may be maintained by a specific enzyme: telomerase, which synthesize telomeric DNA repeats onto chromosome ends, thus stabilize the telomeric length. In human, somatic cells do not express telomerase activity. Therefore, most normal somatic cells have a strictly limited life span and undergo cell death on account of telomere shortening after a defined number of cell division. However, the telomerase activity has recently been found to present in over 80% of human tumors and immortalized cell lines. This indicates that activation of the enzyme telomerase is likely to be an important factor involved in tumorigenesis and cell immortalization.
In the first part of studies, we checked up p16 and Rb gene mutation in human esophageal cancer, and the role of betel nut and smoking and alcohol. 33 patients with esophageal cancer (31 men and 2 women, average age: 57y/o) were enrolled in this study. Collect tissue samples either from operation material or endoscopic tissue biopsy, including tumor and normal parts. Immersed tissue into liquid nitrogen immediately and than stored in -80C. After isolation DNA from cancer tissue, We use polymerase chain reaction (PCR) method to check up P16 DNA methylation, and PCR and SSCP method to check up RB DNA mutation. In the second port of this studies, we collected 24 esophageal cancer patients (men： 21, female：3; mean age 58.6 y/o ) that is pathologically proved as esophageal squamous cell carcinoma by endoscopic examination or operation. We analyzed the telomerase activity and telomerase-associated RNA (hTR and hTERT) of cancer and surround normal tissue. We also collect 7 Barrett’s esophagus patients and analyzed the telomerase activity and its associated RNA (hTR and hTERT).
Our result showed that no significant p16 DNAmethylation nor RB gene mutation found. In the second port of studies, the positive rate of telomerase-associated RNA (hTERT) was 83.3% (20/24) in esophageal cancer part and 16.7% (4/24) in surrounding normal tissue. If compared with those who had smoking, alcohol drinking and betel quid chewing or not, there was no significant difference between substances use and positive rate of hTERT in esophageal cancer. Among those 7 patients who got Barrett’s esophagus, the positive rate of telomerase-associated RNA (hTERT) of the disease part and surrounding normal part was 85.7% and 100 % respective. ( p= 0.6547)
So we couldn’t found mutation pattern of P16 and RB gene. And we also couldn’t explain the role of betel nut chewing playing in esophageal cancer and p16 or RB gene mutation, and protein expression of P16 and RB, and the relationship with betel nut chewing, smoking and alcohol drinking. We also concluded that the telomerase- associated RNA (hTERT) may play an important role in the carcinogenesis of esophagus cancer.
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