XRCC1 Arginine194Tryptophan and GGH-401Cytosine/Thymine polymorphisms are associated with response to platinum-based neoadjuvant chemotherapy in cervical cancer.
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.
Department of Obstetrics and Gynecology, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea.
Kidong
K
Kim
Soon-Beom
SB
Kang
Hyun Hoon
HH
Chung
Jae Weon
JW
Kim
Noh-Hyun
NH
Park
Yong-Sang
YS
Song
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D004268:DNA-Binding Proteins / Q000235:genetics*; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D051549:Glutathione S-Transferase pi / Q000235:genetics; D006801:Humans; D007371:Interferon-gamma / Q000008:administration & dosage; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D000076105:X-ray Repair Cross Complementing Protein 1; D011623:gamma-Glutamyl Hydrolase / Q000235:genetics*
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D015251:Epirubicin; D007371:Interferon-gamma; D016190:Carboplatin; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D011623:gamma-Glutamyl Hydrolase; D017239:Paclitaxel; D002945:Cisplatin; D005472:Fluorouracil