Single Nucleotide Polymorphism (SNP) in RASSF1 and Clinical Outcomes of Breast Cancer Patients Treated with Neoadjuvant Docetaxel/Doxorubicin Chemotherapy.

Abstract

Abstract PurposeThe tumor suppressor gene RASSF1 (Ras association domain family member 1) regulates cell cycle, progression, apoptosis, and microtubule stability, and is inactivated by promoter hypermethylation in breast cancer. We analyzed the SNPs in RASSF1 and their predictive and prognostic value in stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapyMethodsA total of 139 stage II or III breast cancer patients who received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. The patients received three cycles of neoadjuvant chemotherapy followed by curative surgery, and received additional three cycles of docetaxel/doxorubicin chemotherapy as an adjuvant. Germline DNA from peripheral blood mononuclear cells was extracted. The genotypes were performed using Illumina GoldenGate® Assay. We analyzed 3 SNPs in RASSF1 genes: rs3213621 T>C in 3'UTR, rs2073499 G>A in intron, and rs2073498 C>A in exon 3 Ala133Ser.ResultsThe overall radiologic response rate (RR) for neoadjuvant chemotherapy was 79.8% and 10 patients (7.2%) achieved a pathologic complete remission (pCR). None of the SNPs were correlated with radiologic RR or pCR rate. SNP in intron of RASSF1 (rs2073499) was associated with relapse free survival (RFS). RFS was longer in GA/AA genotype than GG genotype (Hazard ratio [HR]=0.374, p=0.034) After adjusting age and hormone status, prognostic value of RASSF1 SNP remained significant (HR=0.393, p=0.050). Other two SNPs were not significantly associated with RFS.ConclusionsThe GA/AA genotype in SNP of RASSF1 (rs2073499) is associated with significantly longer RFS than the GG genotype. Further research is warranted to identify the biologic characteristics of RASSF1. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6061.