Association between KRAS rs61764370 and triple-negative breast cancer—a false positive?: authors' reply

Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgrou...

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Hauptverfasser: Weidhaas, Joanne (VerfasserIn) , Slack, Frank (VerfasserIn) , Miller, Nicola (VerfasserIn) , Harris, Lyndsay (VerfasserIn) , Tuck, David (VerfasserIn) , Zhu, Yong (VerfasserIn) , Zelterman, Daniel (VerfasserIn) , Kerin, Michael (VerfasserIn) , Paranjape, Trupti (VerfasserIn) , Heneghan, Helen (VerfasserIn) , Lindner, Robert (VerfasserIn) , Keane, Florence (VerfasserIn) , Dorairaj, Jemima (VerfasserIn) , Geyda, Kimberly (VerfasserIn) , Pelletier, Cory (VerfasserIn) , Nallur, Sunitha (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 29 July 2011
In: The lancet. Oncology
Year: 2011, Jahrgang: 12, Heft: 8, Pages: 724
ISSN:1474-5488
DOI:10.1016/S1470-2045(11)70163-2
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/S1470-2045(11)70163-2
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1470204511701632
Volltext
Verfasserangaben:Joanne Weidhaas, Frank Slack, Nicola Miller, Lyndsay Harris, David Tuck, Yong Zhu, Daniel Zelterman, Michael Kerin, Trupti Paranjape, Helen Heneghan, Robert Lindner, Florence Keane, Jemima Dorairaj, Kimberly Geyda, Cory Pelletier, Sunitha Nallur

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520 |a Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. - Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). - We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. - rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers. 
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