PURPOSE: 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. DESIGN: 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. CONCLUSION: 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.
PURPOSE: 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. DESIGN: 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 cancerpatients. 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. CONCLUSION: 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: Kristin L White; Robert A Vierkant; Zachary C Fogarty; Bridget Charbonneau; Matthew S Block; Paul D P Pharoah; Georgia Chenevix-Trench; Mary Anne Rossing; Daniel W Cramer; Celeste Leigh Pearce; Joellen M Schildkraut; Usha Menon; Susanne Kruger Kjaer; Douglas A Levine; Jacek Gronwald; Hoda Anton Culver; Alice S Whittemore; Beth Y Karlan; Diether Lambrechts; Nicolas Wentzensen; Jolanta Kupryjanczyk; Jenny Chang-Claude; Elisa V Bandera; Estrid Hogdall; Florian Heitz; Stanley B Kaye; Peter A Fasching; Ian Campbell; Marc T Goodman; Tanja Pejovic; Yukie Bean; Galina Lurie; Diana Eccles; Alexander Hein; Matthias W Beckmann; Arif B Ekici; James Paul; Robert Brown; James M Flanagan; Philipp Harter; Andreas du Bois; Ira Schwaab; Claus K Hogdall; Lene Lundvall; Sara H Olson; Irene Orlow; Lisa E Paddock; Anja Rudolph; Ursula Eilber; Agnieszka Dansonka-Mieszkowska; Iwona K Rzepecka; Izabela Ziolkowska-Seta; Louise Brinton; Hannah Yang; Montserrat Garcia-Closas; Evelyn Despierre; Sandrina Lambrechts; Ignace Vergote; Christine Walsh; Jenny Lester; Weiva Sieh; Valerie McGuire; Joseph H Rothstein; Argyrios Ziogas; Jan Lubinski; Cezary Cybulski; Janusz Menkiszak; Allan Jensen; Simon A Gayther; Susan J Ramus; Aleksandra Gentry-Maharaj; Andrew Berchuck; Anna H Wu; Malcolm C Pike; David Van Denberg; Kathryn L Terry; Allison F Vitonis; Jennifer A Doherty; Sharon E Johnatty; Anna Defazio; Honglin Song; Jonathan Tyrer; Thomas A Sellers; Catherine M Phelan; Kimberly R Kalli; Julie M Cunningham; Brooke L Fridley; Ellen L Goode Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-03-19 Impact factor: 4.254
Authors: Sharon E Johnatty; Jonathan Beesley; Bo Gao; Xiaoqing Chen; Yi Lu; Matthew H Law; Michelle J Henderson; Amanda J Russell; Ellen L Hedditch; Catherine Emmanuel; Sian Fereday; Penelope M Webb; Ellen L Goode; Robert A Vierkant; Brooke L Fridley; Julie M Cunningham; Peter A Fasching; Matthias W Beckmann; Arif B Ekici; Estrid Hogdall; Susanne K Kjaer; Allan Jensen; Claus Hogdall; Robert Brown; Jim Paul; Sandrina Lambrechts; Evelyn Despierre; Ignace Vergote; Jenny Lester; Beth Y Karlan; Florian Heitz; Andreas du Bois; Philipp Harter; Ira Schwaab; Yukie Bean; Tanja Pejovic; Douglas A Levine; Marc T Goodman; Michael E Camey; Pamela J Thompson; Galina Lurie; Joellen Shildkraut; Andrew Berchuck; Kathryn L Terry; Daniel W Cramer; Murray D Norris; Michelle Haber; Stuart MacGregor; Anna deFazio; Georgia Chenevix-Trench Journal: Gynecol Oncol Date: 2013-08-01 Impact factor: 5.482
Authors: Sharon E Johnatty; Jonathan P Tyrer; Siddhartha Kar; Jonathan Beesley; Yi Lu; Bo Gao; Peter A Fasching; Alexander Hein; Arif B Ekici; Matthias W Beckmann; Diether Lambrechts; Els Van Nieuwenhuysen; Ignace Vergote; Sandrina Lambrechts; Mary Anne Rossing; Jennifer A Doherty; Jenny Chang-Claude; Francesmary Modugno; Roberta B Ness; Kirsten B Moysich; Douglas A Levine; Lambertus A Kiemeney; Leon F A G Massuger; Jacek Gronwald; Jan Lubiński; Anna Jakubowska; Cezary Cybulski; Louise Brinton; Jolanta Lissowska; Nicolas Wentzensen; Honglin Song; Valerie Rhenius; Ian Campbell; Diana Eccles; Weiva Sieh; Alice S Whittemore; Valerie McGuire; Joseph H Rothstein; Rebecca Sutphen; Hoda Anton-Culver; Argyrios Ziogas; Simon A Gayther; Aleksandra Gentry-Maharaj; Usha Menon; Susan J Ramus; Celeste L Pearce; Malcolm C Pike; Daniel O Stram; Anna H Wu; Jolanta Kupryjanczyk; Agnieszka Dansonka-Mieszkowska; Iwona K Rzepecka; Beata Spiewankiewicz; Marc T Goodman; Lynne R Wilkens; Michael E Carney; Pamela J Thompson; Florian Heitz; Andreas du Bois; Ira Schwaab; Philipp Harter; Jacobus Pisterer; Peter Hillemanns; Beth Y Karlan; Christine Walsh; Jenny Lester; Sandra Orsulic; Stacey J Winham; Madalene Earp; Melissa C Larson; Zachary C Fogarty; Estrid Høgdall; Allan Jensen; Susanne Kruger Kjaer; Brooke L Fridley; Julie M Cunningham; Robert A Vierkant; Joellen M Schildkraut; Edwin S Iversen; Kathryn L Terry; Daniel W Cramer; Elisa V Bandera; Irene Orlow; Tanja Pejovic; Yukie Bean; Claus Høgdall; Lene Lundvall; Ian McNeish; James Paul; Karen Carty; Nadeem Siddiqui; Rosalind Glasspool; Thomas Sellers; Catherine Kennedy; Yoke-Eng Chiew; Andrew Berchuck; Stuart MacGregor; Paul D P Pharoah; Ellen L Goode; Anna deFazio; Penelope M Webb; Georgia Chenevix-Trench Journal: Clin Cancer Res Date: 2015-07-07 Impact factor: 12.531