title: Genetic polymorphisms as predictive and prognostic biomarkers in gynecological cancers: a systematic review.
abstract: OBJECTIVE
  Numerous studies have explored the potential role of genetic polymorphisms as predictive or prognostic biomarkers in gynecologic malignancies. A systematic review for all eligible polymorphisms has not yet been reported. The aim of this study was to summarize the current status of the field and provide direction for future research.
  
  
  METHODS
  We searched literature databases (MEDLINE, EMBASE, Cochrane) from 2006 to April 2011 to identify studies evaluating the association between gene polymorphisms and clinical outcome in ovarian, endometrial, cervical, or vulvar cancer. The main outcome measures were overall survival (OS) and progression-free survival (PFS). Studies reporting relationships between polymorphisms and toxicity were also included.
  
  
  RESULTS
  Sixty two studies met the inclusion criteria. The median sample size was 140. Most of the included studies (n=50, 81%) were conducted in ovarian cancer patients. Almost a third assessed potential predictive associations between gene polymorphism and outcome in ovarian cancer. The most commonly evaluated genes were ERCC1, VEGF, ABCB1 (MDR), and GSTP1. Most studies (n=44, 71%) were observational case-series. Only four studies (6%) included a validation arm and patient population ethnicity was explicitly stated only in 27% of included studies.
  
  
  CONCLUSIONS
  No consistent association between any gene polymorphism and clinical outcome in gynecological cancers has been found across studies. There is incomplete adherence to the REMARK guidelines and inadequate methodology reporting in most studies. Moving forward, analysis of large trial-based clinical samples; adherence to the highest methodological standards, and focus on validation analyses are necessary to identify clinically useful pharmacogenomic biomarkers of outcome.
authors: Division of Medical Oncology, Princess Margaret Hospital, University of Toronto, Ontario, Canada. ivan.padilla@uhn.on.ca
authors: Ivan
authors: I
authors: Diaz-Padilla
authors: Eitan
authors: E
authors: Amir
authors: Sharon
authors: S
authors: Marsh
authors: Geoffrey
authors: G
authors: Liu
authors: Helen
authors: H
authors: Mackay
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D005260:Female; D005833:Genital Neoplasms, Female / Q000235:genetics*; D006801:Humans; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011379:Prognosis
chemical_list: D014408:Biomarkers, Tumor