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XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine polymorphisms are associated with response to platinum-based neoadjuvant chemotherapy in cervical cancer

Cited 31 time in Web of Science Cited 30 time in Scopus
Authors
Kim, Kidong; Kang, Soon-Beom; Chung, Hyun Hoon; Kim, Jae Weon; Park, Noh-Hyun; Song, Yong-Sang
Issue Date
2008-10-15
Publisher
Elsevier
Citation
Gynecol Oncol. 2008;111(3):509-515
Keywords
AdultAgedAntineoplastic Combined Chemotherapy Protocols/*therapeutic useCarboplatin/administration & dosageChemotherapy, AdjuvantCisplatin/administration & dosageDNA-Binding Proteins/*geneticsEpirubicin/administration & dosageFemaleFluorouracil/administration & dosageGlutathione S-Transferase pi/geneticsHumansInterferon-gamma/administration & dosageMethylenetetrahydrofolate Dehydrogenase (NADP)/geneticsMiddle AgedNeoadjuvant TherapyPaclitaxel/administration & dosagePolymorphism, Single NucleotideRetrospective StudiesUterine Cervical Neoplasms/*drug therapy/*genetics/metabolismgamma-Glutamyl Hydrolase/*genetics
Abstract
OBJECTIVE: The objective of this study was to evaluate the association of single nucleotide polymorphisms (SNPs) of genes which are involved in DNA synthesis and repair with the response to platinum-based neoadjuvant chemotherapy (NAC) and disease-free survival (DFS) in patients with cervical cancer who were treated with NAC followed by radical hysterectomy. METHODS: A retrospective review was performed on 66 patients with cervical cancer who were treated with NAC followed by radical hysterectomy in our institute between January 1999 and February 2007. DNA was extracted from the paraffin-embedded, formalin-fixed tissue blocks of hysterectomy specimens. The genotypes of SNPs (MTHFR 677Cytosine/Thymine, XRCC1 Arginine194Tryptophan, GGH-401Cytosine/Thymine, and GSTP1 Isoleucine105Valine) were determined using a single base primer extension assay. The association of SNP genotypes with the response to NAC, which was measured by physical and colposcopic examinations, was evaluated. In addition, DFS based on SNP genotypes was examined. RESULTS: The genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P=0.023 for XRCC1 Arginine194Tryptophan; P=0.046 for GGH-401Cytosine/Thymine). However, the genotypes of MTHFR 677Cytosine/Thymine and GSTP1 Isoleucine105Valine were not associated with the response to NAC. In subgroup analysis with 39 patients who were treated with regimens containing 5-fluorouracil (5-FU), the genotypes of GGH-401Cytosine/Thymine were significantly associated with the response to NAC (P=0.039). In multifactor dimensionality reduction (MDR) analysis, the combination of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine genotypes was associated with the response to NAC (P<0.001). However, no SNP genotypes were associated with DFS, but the cisplatin dose intensity of NAC was associated with DFS. CONCLUSIONS: The genotypes of XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine were associated with the response to NAC in patients with cervical cancer. However, no SNP genotypes were associated with DFS.
ISSN
1095-6859 (Electronic)
Language
English
URI
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=18851872

http://www.sciencedirect.com/science?_ob=MImg&_imagekey=B6WG6-4TNG597-2-5&_cdi=6814&_user=168665&_orig=search&_coverDate=12%2F31%2F2008&_sk=998889996&view=c&wchp=dGLbVzz-zSkzV&md5=a4fd3df95d5d3f7e3f1bd40512d1ec84&ie=/sdarticle.pdf

http://hdl.handle.net/10371/68054
DOI
https://doi.org/10.1016/j.ygyno.2008.08.034
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College of Medicine/School of Medicine (의과대학/대학원)Obstetrics & Gynecology (산부인과전공)Journal Papers (저널논문_산부인과학전공)
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