Association between Mad1 G558A and ERCC1 C8092A polymorphisms and response to induction chemotherapy in advanced ovarian carcinoma

• Published in: Journal of clinical oncology Vol. 27; no. 15_suppl; p. 5568
• Main Authors: Figueroa, P., Castro Hernández, C., Santibáñez Andrade, M., Díaz Romero, M., Morales Vázquez, F., Gallardo Rincón, D., Herrera Montalvo, L. A.
• Format: Journal Article
• Language: English
• Published: 20.05.2009
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/jco.2009.27.15_suppl.5568

Abstract only 5568 Background: Platinum and taxane remain active drugs in the treatment of ovarian cancer.The polymorphism C8092A of ERCC1 is involved in NER pathway of platinum induced damage DNA and Mad1 G558A with modulation of the chromosomal segregation. As primary aim we evaluated the influence of these polymorphisms in the chemotherapy response. Methods: ERCC1 C8092A and Mad1 G558A polymorphism allelic and genotypic frequency was determined on DNA isolated from blood tumor samples by PCR and specific digestion in 56 patients with cancer of advanced ovary who received induction chemotherapy with 3 courses of paclitaxel 175 mg/m 2 and AUC6 carboplatin every 3 weeks. Informed consent was obtained for all subjects and the study was approved by the hospital ethic committee. Results: Between January 2008 to June 2008, 56 women were evaluated, with age media was 53 years, majority characteristics were stages III (66.9%) 37 and IV (33.1%) 19 patients, histology serous papillary (94.6%) high-grade differenced (73.2%). Mad1 genotype were 7 G/G (12.5%), 30 were G/A (53.6%), 19 were A/A( 33.9%), and ERCC1 genotype were 20 C/C (35.7%), 30 were C/A (53.6%) and 6 were A/A (10.7%). All biochemical response by Rustin criteria was noted in 89.28%. Allele A for Mad1 is more frequently observed in patients with ovarian carcinoma versus in mexican healthy women (61% vs. 49%) and suggests the possibility that the polymorphism of Mad1 is a marker of risk for ovary cancer (RR = 1, 15, p < 0, 05). According our aim we observed a higher response in allele G (91.89%) than allele A (87.75%) of Mad1 (p < 0.10).Interestingly allele A of ERRC1 was not associated greater response (88.88% vs. 92%, p > 0.10). Additionally we evaluated the predictive value of Ca 125 return to normal range after 3 chemotherapy courses, showed in 22 patients (39.28%) in univariate analysis we noted that allele G of Mad1 has been linked to improved response (p = 0.041). Conclusions: This is the first study in ovary cancer that evaluates predictive value of two SNP, one of them involved in the spindle checkpoint and the other in DNA repair mechanism (NER), suggesting to Mad1 G558A likely risk polymorphism for ovary cancer and response to chemotherapy based on taxanes, which may be a predictive biomarker. No significant financial relationships to disclose.