[Effects of genetic polymorphisms of ethanol-metabolizing enzymes on alcohol drinking behaviors].

BACKGROUND/AIMS: Genetic variations of ethanol-metabolizing enzymes can affect alcohol drinking behavior. The aims of this study were to investigate and compare the distributions of these genetic polymorphisms between a healthy control group and a heavy drinker group which included an alcoholic liver cirrhosis group. METHODS: Genotypes of ADH2, ALDH2, CYP2E1, and catalase were identified by polymerase chain reaction and restriction fragment length polymorphism. Genomic DNA was extracted from peripheral leukocytes in 42 healthy controls, 12 heavy drinkers, and 30 alcoholic liver cirrhosis patients. RESULTS: 1) The genotype frequencies of ALDH2 (1*1), ADH2 (1*1), CYP2E1 (c1c1), and catalase1 (TT) were 69%, 55%, 38%, and 12%, respectively in healthy Korean males. 2) There was a significant difference in the distribution of the genetic polymorphism of ALDH2 between the control group and heavy drinker group (12 heavy drinkers and 30 alcoholic liver cirrhosis patients). The genotype frequency of ALDH2 mutant, ALDH2 (1*2) and ALDH2 (2*2) in the heavy drinker group (12%) was significantly lower than that in the control group (30%). 3) We didn't find anyone with ALDH2 homozygote mutant (DD) in the heavy drinker group. 4) There was no significant difference in the distribution of genetic polymorphisms in ADH2, CYP2E1 and catalase1 between the two groups. CONCLUSIONS: These results suggest that the absence of ALDH2 mutant genotype is strongly related to heavy drinking behavior. We can not prove, however, any evidence that the polymorphisms of other ethanol-metabolizing enzymes are associated with the determination of alcohol-drinking behavior.

Concurrent FP (5-fluorouracil, cisplatin) Chemoradiotherapy for Patients with Esophageal Cancer.

PURPOSE: The outcomes of a surgical approach for patients with an esophageal carcinoma remain unsatisfactory despite its high complication rates. We conducted a phase II trial, using combined FP (5-fluorouracil and cisplatin) chemotherapy and concurrent radiotherapy, as a definitive therapy for patients with esophageal cancer. MATERIALS AND METHODS: Patients with histologically proven esophageal cancer were enrolled onto this study. The treatment consisted of four courses of chemotherapy and six and a half weeks of radiotherapy. The patients received chemotherapy in weeks 1, 5, 12 and 16 (5-fluorouracil 1, 000 mg/m2 on days 1 to 4 and cisplatin 75 mg/m2 on day 1). Radiotherapy was administered at a dose of 59.4 Gy, in five 1.8 Gy fractions a week. RESULTS: A total of 22 eligible patients entered the study. Of the 19 evaluable patients, a complete response occurred in 7 (37%), and a partial response in 8 (42%). After a median follow-up of 35 months, the overall survival rate was 32% at three years and the median survival was 11 months. Fourteen (64%) received planned dose of radio-therapy and 13 (59%) received more than three courses of chemotherapy. However, there was no difference in three-year survival rates between the patients that received less than three courses of chemotherapy and those that received three or more courses (31% vs. 32%). The major treatment related toxicity was mucositis, which developed in every patient, with grades III or IV in thirteen (59%) patients. During the treatment, the patients lost, on average, 3.8% of their body weight. The mean hospital stay was 23 days, with a total duration of treatment of 74 days. CONCLUSION: S: Concurrent FP chemoradiotherapy was effective as a definitive therapy for patients with esophageal cancer. The major toxicity was mucositis. Although the treatment was relatively feasible, a randomized trial of reduced courses of chemotherapy is warranted.