CYP2D6 and NAT2 Polymorphism in HBV Associated in Hepatocellular Carcinoma Patients in Korea

PURPOSE: CYP2D6 and N-acetyltransferase (NAT2) are polymorphic enzymes which are expressed in the hepatocyte in a genotype-determined manner. They are known to be involved in the inactivation and activation of various mutagens and carcinogens, respectively. The activities of the two enzyme systems are associated with the genetic susceptibility of many human cancers. METHODS: This study was performed to determine the genotype frequencies of the two enzyme systems in primary hepatocellular carcinoma patients and healthy controls. One hundred healthy controls and 55 liver cancer patients were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: In the healthy controls, the CYP2D6 wild type allele frequency was 0.985 and the CYP2D6*4 frequency was 0.015. No CYP2D6 poor-metabolizer was detected. No significant differences were found in the hepatocellular carcinoma patients group. Among the controls, the frequencies of F, S1, S2 and S3 alleles of the NAT2 system were 0.725, 0.01, 0.14 and 0.125, respectively. The genotype frequencies were found to be 0.91 for the rapid acetylator and 0.09 for the slow acetylator. No significant differences were found in the hepatocellular carcinoma group. CONCLUSION: The distribution of CYP2D6 and NAT2 polymorphism is very unique in the Korean population, as characterized by the extremely low frequency of CYP2D6 poor-metabolizer and NAT2 slow acetylator. CYP2D6 and NAT2 polymorphisms did not seem to play an important role in the hepatic carcinogenesis in the Korean population.

The influence of gastrectomy on the change of bone metabolism and bone density

OBJECTIVES: Abnormalities of bone metabolism could be followed in gastrectomized patients as a late complication. Nowadays, many biochemical and radiologic measurements are applied to detect these abnormalities. The aim of our study is to determine the valuable parameter as an appropriate screening test during long-term follow-up periods and define the usefulness of new biochemical markers for bone metabolism by comparing with traditional markers. METHODS: Fifteen patients who had undergone partial gastrectomy were chosen randomly and fifteen healthy controls were compared. Then, several biochemical and radiologic tests were measured. We excluded subjects who proved to have other causes of bone metabolism abnormalities. Ten patients and 10 controls were finally selected. RESULTS: Comparing the data with those of a corresponding control group, the lumbar bone density measured by quantitative computed tomography (QCT) was statistically significantly lower in the patient group (p +ADw- 0.01). The urinary deoxypyridinoline, a biochemical marker for bone resorption, was statistically higher in the patient group (p +ADw- 0.025). Osteocalcin, Procollagen I C-terminal peptide (PICP) and Type I collagen C-terminal telopeptide (ICTP) were slightly but not significantly higher in the patient group. The serum parathyroid hormone (PTH) and 25-hydroxy vitamin D levels were similar in both groups. CONCLUSION: We could suggest that urinary deoxypyridinoline and QCT are appropriate parameters as screening tests for the detection of bone metabolism abnormalities in gastrectomized patients during long-term follow-up. Urinary deoxypyridinoline may be a simple and rapid test which could replace cumbersome 24-hour urinary hydroxyproline.

Remnant Gastric Cancer

Remnant gastric cancer is defined broadly as cancer that develops in the remnant stomach after the resection of nonmalignant or malignant lesions. Generally speaking, remnant gastric cancer is defined as its interval between previous gastrectomy and the detection of remnant gastric cancer must be over 10 years in the previous malignant or nonmalignant lesions. From Aug. 1988 to Dec. 1995, fifteen patients who were operated as remnant gastric cancer (broad definition) in Hanyang Universty Hospital was reviewed as follows. Sex distribution was 12 cases in male and 3 cases in female. Peak incidence of age was 5th and 6th decades.The T.N.M. staging was at first operation: benign disease in 6 cases, stage I in 4 cases, stage IIIa in 1 case, stage IIIb in 2 cases and unknown stage in 2 cases, and at 2nd operation; stage I in 3 cases,stage II in 1 case, stage IIIa in 2 cases, stage IIIb in 5 cases, stage IV in 4 cases. The interval between first and second operation was as follows : less than 5 years in 4 cases, 5 to 10 years in 2 cases, 10 to 15 years in 3 cases, and over 20 years in 6 cases. The procedure at first operation was Billroth II procedure, and the procedure at 2nd operation was as follows: total gastrectomy with Roux-en-Y esophagojejunostomy in 12 cases,total gastrectomy with loop esophagojejunostomy in 2 cases,dismentling partial gastrectomy with Roux-en-Y gastrojejunostomy in 1 case. In our opinion,early diagnosis of remnant carcinoma following gastric surgery by the endoscopic follow up and aggresive surgery are important to improve disease free interval and patient survival.