ABSTRACT
Objective To explore the function of ERCC2/XPD polymorphisms in the repair of DNA damage induced by UVC. Methods Plas?mids stably expressing ERCC2/XPD rs13181 AA(Lys751)and ERCC2/XPD rs13181 CC(Gln751)were transfected into Chinese hamster ovary cells,and the stable ERCC2 transfected cell lines were obtained. MTT assay was used to compare the inhibitory rates of the transfected cells treated with UVC at different irradiation intensity. The DNA damage repair ability of the transfected cells treated with UVC for 1,3,6 and 24 h was detected by modified comet assay. Results Compared with UV5ERCC2(CC),UV5ERCC2(CC) was more sensitive to UVC with decreased cell viability. DNA damage level of UV5ERCC2(CC) cells was more serious than UV5ERCC2(CC). Conclusion DNA repair capacity of ERCC2/XPD rs13181A allelic is lower than its wild?type,suggesting that ERCC2/XPDpolymorphisms play a critical role in UVC?induced DNA damage repair.
ABSTRACT
PURPOSE: The expressions of low levels of ERCC1 (excision repair crosscomplementation group 1) and ERCC2/XPD (excision repair cross- complementation group 2) have been studied in order to find a potential marker for predicting the prognosis or treatment response in cancer patients. However, polymorphisms in these genes have been rarely evaluated in terms of predicting the survival of cancer patients. MATERIALS AND METHODS: We investigated whether these polymorphisms had an effect on the response to chemotherapy and on the survival in 109 patients, with non-small-cell lung cancer, treated with cisplatin plus gemcitabine, paclitaxel or docetaxel. The polymorphisms of ERCC1 Asn118Asn (C->T), ERCC2 Lys751Gln and Asp312Asn were evaluated using a SNaPshot kit. RESULTS: The treatment responses showed no statistically significant differences according to the polymorphisms of ERCC1 Asn118Asn, ERCC2 Lys751Gln or Asp312Asn. The median survival time was 376 days (95% CI, 291~488). The overall survival rate showed no significant difference according to age, sex, chemotherapy regimen, clinical stage or sequential radiation therapy. The polymorphisms of ERCC2 Lys751Gln and Asp312Asn did not affect the survival of the patients (p=0.4711 and 0.4542, respectively). The polymorphism of ERCC1 Asn118Asn, chemotherapy response, performance status and body weight loss had effect on the overall survival of the patients (p=0.0001, 0.0001, 0.0176 and 0.0082 respectively). As for survival rate, according to the polymorphism in ERCC1 Asn118Asn, the median survival time in those patients showing the wild genotype (C/C) was 480 days (95% CI, 333~544), which was statistically significant compared with the 281 days for the patients with the variant genotype (T/T, C/T) (hazard ratio 3.497) (95% CI, 214~376). CONCLUSION: It is suggested that the presence of the wild genotype in ERCC1 Asn118Asn, in non-small-cell lung cancer patients treated with cisplatin based chemotherapy, was a surrogate marker for predicting a better survival.