OBJECTIVES: The aim of the study was to assess whether the genetic polymorphisms were associated with the tumor response in patients treated with platinum-based neoadjuvant chemotherapy (NAC) for bulky cervical cancer. METHODS: We retrospectively reviewed the clinical data and recruited paraffin-embedded, formalin-fixed tissues of 36 patients with bulky cervical carcinoma. All patients underwent two or three cycles of platinum-based NAC followed by radical hysterectomy. We determined the genotypes of each single nucleotide polymorphism (SNP) of ERCC1, ERCC2, GGH, GSTP1, MTHFR, SLC19A1 and XRCC1 using single base primer extension assay. RESULTS: The response to platinum-based NAC was higher in patients with SNP of XRCC1 R399Q (P=0.015), and there was a significant increased chance of treatment response in women with the G/G genotype (OR 38.0; 95% CI 1.66-870.45; P=0.023). The probability of response was also higher in patients with SNP of SLC19A1 6318C/T (P=0.032). There were dose-dependent influence of the number of alleles on the response to platinum-based chemotherapy (chi2 test for linear-by-linear association; P=0.009 for XRCC1 R399Q and P=0.017 for SLC19A1 6318C/T, respectively). Moreover, the multifactor dimensionality reduction (MDR) analysis documented that the combinations of XRCC1 R399Q and GGH-401C/T genetic polymorphisms were significantly associated with response to chemotherapy (P<0.0001). CONCLUSIONS: Genetic polymorphism of XRCC1 R399Q is associated with response to platinum-based NAC in bulky cervical cancer, and MDR analysis documented association between gene-gene interaction of XRCC1 R399Q and treatment response.
OBJECTIVES: The aim of the study was to assess whether the genetic polymorphisms were associated with the tumor response in patients treated with platinum-based neoadjuvant chemotherapy (NAC) for bulky cervical cancer. METHODS: We retrospectively reviewed the clinical data and recruited paraffin-embedded, formalin-fixed tissues of 36 patients with bulky cervical carcinoma. All patients underwent two or three cycles of platinum-based NAC followed by radical hysterectomy. We determined the genotypes of each single nucleotide polymorphism (SNP) of ERCC1, ERCC2, GGH, GSTP1, MTHFR, SLC19A1 and XRCC1 using single base primer extension assay. RESULTS: The response to platinum-based NAC was higher in patients with SNP of XRCC1R399Q (P=0.015), and there was a significant increased chance of treatment response in women with the G/G genotype (OR 38.0; 95% CI 1.66-870.45; P=0.023). The probability of response was also higher in patients with SNP of SLC19A16318C/T (P=0.032). There were dose-dependent influence of the number of alleles on the response to platinum-based chemotherapy (chi2 test for linear-by-linear association; P=0.009 for XRCC1R399Q and P=0.017 for SLC19A16318C/T, respectively). Moreover, the multifactor dimensionality reduction (MDR) analysis documented that the combinations of XRCC1R399Q and GGH-401C/T genetic polymorphisms were significantly associated with response to chemotherapy (P<0.0001). CONCLUSIONS: Genetic polymorphism of XRCC1R399Q is associated with response to platinum-based NAC in bulky cervical cancer, and MDR analysis documented association between gene-gene interaction of XRCC1R399Q and treatment response.
Authors: Sook Wah Yee; Li Gong; Ilaria Badagnani; Kathleen M Giacomini; Teri E Klein; Russ B Altman Journal: Pharmacogenet Genomics Date: 2010-11 Impact factor: 2.089
Authors: R Stephanie Huang; Shiwei Duan; Emily O Kistner; Christine M Hartford; M Eileen Dolan Journal: Mol Cancer Ther Date: 2008-09-02 Impact factor: 6.261
Authors: William D Figg; Cindy H Chau; Ravi A Madan; James L Gulley; Rui Gao; Tristan M Sissung; Shawn Spencer; Melony Beatson; Jeanny Aragon-Ching; Seth M Steinberg; William L Dahut Journal: Clin Genitourin Cancer Date: 2013-05-17 Impact factor: 2.872