PMID- 21751198
OWN - NLM
STAT- MEDLINE
DCOM- 20120327
LR  - 20151119
IS  - 1097-0142 (Electronic)
IS  - 0008-543X (Linking)
VI  - 118
IP  - 3
DP  - 2012 Feb 1
TI  - Xeroderma pigmentosum complementation group C single-nucleotide polymorphisms in 
      the nucleotide excision repair pathway correlate with prolonged progression-free 
      survival in advanced ovarian cancer.
PG  - 689-97
LID - 10.1002/cncr.26329 [doi]
AB  - BACKGROUND: The nucleotide excision repair (NER) pathway is the principal DNA 
      repair pathway for removing bulky platinum DNA adducts. Suboptimal DNA repair may 
      lead to improved response to platinum agents. The objective of this study was to 
      determine whether single-nucleotide polymorphisms (SNPs) in NER pathway genes 
      could be markers of platinum response in ovarian cancer. METHODS: The authors 
      identified patients with advanced-stage, papillary serous ovarian cancer who 
      underwent primary cytoreductive surgery followed by platinum-based chemotherapy. 
      DNA was isolated from peripheral blood specimens. Twenty-two SNPs within NER 
      genes (xeroderma pigmentosum [XP] complementation group A [XPA], XPB/excision 
      repair cross-complementing rodent repair deficiency, complementation group 3 
      [ERCC3], XPC, XPD/ERCC2, XPF/ERCC4, XPG/ERCC5, Cockayne syndrome group B protein 
      [CSB]/ERCC8, ERCC1) were genotyped using polymerase chain reaction analysis. 
      RESULTS: In total, 139 patients with stage III and IV papillary serous ovarian 
      cancer were genotyped. The XPC (reference SNP 3731108 [rs3731108]) 
      adenosine-guanine (AG)/AA genotype versus the GG genotype was associated with 
      prolonged a progression-free survival (PFS) of 21.3 months versus 13.4 months 
      (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.42-0.95; P = .03). The 
      XPC (rs1124303) guanosine-thymidine (GT)/GG genotype versus the TT genotype was 
      associated with a prolonged PFS of 22.8 months versus 14.9 months (HR, 0.47; 95% 
      CI, 0.24-0.94; P = .03). The XPC poly(AT) (PAT) (-/+)/(-/-) genotype versus the 
      (+/+) genotype was associated with a prolonged PFS of 17 months versus 11.6 
      months (HR, 0.56; 95% CI, 0.36-0.89; P = .01). The XPF/ERCC4 (rs12926685) 
      cytidine-thymidine (CT)/CC genotype versus the TT genotype was associated with a 
      prolonged PFS of 16.7 months versus 12.4 months (HR, 0.63; 95% CI, 0.41-0.95; P = 
      .03). On multivariate analysis adjusting for breast cancer (BRCA) gene and 
      cytoreductive surgery status, the XPC SNPs remained significantly associated with 
      prolonged PFS. CONCLUSIONS: The current results indicated that XPC is a key 
      component of the NER pathway that participates in DNA damage repair. SNPs in the 
      XPC gene may represent novel markers of ovarian cancer response to platinum-based 
      chemotherapy.
CI  - Copyright (c) 2011 American Cancer Society.
FAU - Fleming, Nicole D
AU  - Fleming ND
AD  - Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, 
      Cedars-Sinai Women's Cancer Research Institute, Los Angeles, California 90048, 
      USA.
FAU - Agadjanian, Hasmik
AU  - Agadjanian H
FAU - Nassanian, Hoorig
AU  - Nassanian H
FAU - Miller, Carl W
AU  - Miller CW
FAU - Orsulic, Sandra
AU  - Orsulic S
FAU - Karlan, Beth Y
AU  - Karlan BY
FAU - Walsh, Christine S
AU  - Walsh CS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110712
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 156533-34-5 (XPC protein, human)
SB  - IM
EIN - Cancer. 2012 Nov 1;118(21):5450
MH  - Adenocarcinoma, Papillary/*genetics/mortality/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Cystadenocarcinoma, Serous/*genetics/mortality/pathology
MH  - DNA Repair/*genetics
MH  - DNA, Neoplasm/genetics
MH  - DNA-Binding Proteins/*genetics
MH  - Female
MH  - Humans
MH  - Middle Aged
MH  - Ovarian Neoplasms/*genetics/mortality/pathology
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide/*genetics
MH  - Prognosis
MH  - Survival Rate
EDAT- 2011/07/14 06:00
MHDA- 2012/03/28 06:00
CRDT- 2011/07/14 06:00
PHST- 2011/03/29 00:00 [received]
PHST- 2011/05/10 00:00 [revised]
PHST- 2011/05/11 00:00 [accepted]
PHST- 2011/07/14 06:00 [entrez]
PHST- 2011/07/14 06:00 [pubmed]
PHST- 2012/03/28 06:00 [medline]
AID - 10.1002/cncr.26329 [doi]
PST - ppublish
SO  - Cancer. 2012 Feb 1;118(3):689-97. doi: 10.1002/cncr.26329. Epub 2011 Jul 12.