BACKGROUND: Aberrant methylation of some cancer-related genes has been reported to correlate with sensitivity to chemotherapeutic agents. The present study was designed to determine whether DNA methylation in six cancer-related genes affects recurrence of gastric cancer in patients who received 5-fluorouracil-based adjuvant chemotherapy. METHODS: The methylation status of six genes, MGMT, CHFR, hMLH1, p16INK4a, E-cadherin, and Runx3, was analyzed in 56 surgically resected gastric cancer tissue specimens by methylation-specific polymerase chain reaction. Of the 56 patients who underwent surgical resection, 38 received 5-fluorouracil (5-FU)-based adjuvant chemotherapy postoperatively (adjuvant group), whereas the other 18 (32%) did not (surgery group). RESULTS: There were no significant differences between the two groups with respect to sex, cancer differentiation, depth of tumor invasion, lymph node metastasis, lymphatic invasion, vascular invasion and tumor stage. Among the genes, methylation of p16INK4a showed a significant correlation with longer survival in the 38 patients of the adjuvant group, but not in the 18 patients of the surgery group. A multivariate analysis identified p16INK4a methylation to be an independent factor predicting a longer recurrence-free period under 5-FU-based adjuvant chemotherapy. CONCLUSIONS: The present study demonstrated for the first time that gastric cancer patients with p16INK4a methylation specifically benefit from 5-FU-based adjuvant chemotherapy.
BACKGROUND: Aberrant methylation of some cancer-related genes has been reported to correlate with sensitivity to chemotherapeutic agents. The present study was designed to determine whether DNA methylation in six cancer-related genes affects recurrence of gastric cancer in patients who received 5-fluorouracil-based adjuvant chemotherapy. METHODS: The methylation status of six genes, MGMT, CHFR, hMLH1, p16INK4a, E-cadherin, and Runx3, was analyzed in 56 surgically resected gastric cancer tissue specimens by methylation-specific polymerase chain reaction. Of the 56 patients who underwent surgical resection, 38 received 5-fluorouracil (5-FU)-based adjuvant chemotherapy postoperatively (adjuvant group), whereas the other 18 (32%) did not (surgery group). RESULTS: There were no significant differences between the two groups with respect to sex, cancer differentiation, depth of tumor invasion, lymph node metastasis, lymphatic invasion, vascular invasion and tumor stage. Among the genes, methylation of p16INK4a showed a significant correlation with longer survival in the 38 patients of the adjuvant group, but not in the 18 patients of the surgery group. A multivariate analysis identified p16INK4a methylation to be an independent factor predicting a longer recurrence-free period under 5-FU-based adjuvant chemotherapy. CONCLUSIONS: The present study demonstrated for the first time that gastric cancerpatients with p16INK4a methylation specifically benefit from 5-FU-based adjuvant chemotherapy.
Authors: Manel Esteller; Gianluca Gaidano; Steven N Goodman; Vittorina Zagonel; Daniela Capello; Barbara Botto; Davide Rossi; Annunziata Gloghini; Umberto Vitolo; Antonino Carbone; Stephen B Baylin; James G Herman Journal: J Natl Cancer Inst Date: 2002-01-02 Impact factor: 13.506
Authors: M Weller; J Rieger; C Grimmel; E G Van Meir; N De Tribolet; S Krajewski; J C Reed; A von Deimling; J Dichgans Journal: Int J Cancer Date: 1998-12-18 Impact factor: 7.396