No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

• Published in: Gynecologic oncology Vol. 141; no. 2; pp. 386 - 401
• Main Authors: van der Baan, Frederieke H, Johnatty, Sharon E, Antonenkova, Natalia N, Apicella, Carmel, Baglietto, Laura, Balleine, Rosemary, Barrowdale, Daniel, Benitez, Javier, Berger, Raanan, Beuselinck, Benoit, Bisogna, Maria, Bojesen, Stig E, Brunet, Joan, Brüning, Thomas, Bunker, Clareann H, Caligo, Maria A, Cybulski, Cezary, de la Hoya, Miguel, Devilee, Peter, Diez, Orland, du Bois, Andreas, Duran, Mercedes, Easton, Douglas F, Eccles, Diana, Fasching, Peter A, Fletcher, Olivia, Friebel, Tara, Gayther, Simon A, Gentry-Maharaj, Aleksandra, Gerdes, Anne-Marie, Greene, Mark H, Grip, Mervi, Gschwantler Kaulich, Daphne, Haeberle, Lothar, Haiman, Christopher A, Hansen, Thomas V.O, Harter, Philipp, Hartikainen, Jaana M, Healey, Sue, Henderson, Brian E, Imyanitov, Evgeny N, Jensen, Allan, Karlan, Beth Y, Kjaer, Susanne K, Knight, Julia A, Knol-Bout, Jacoba P, Kosma, Veli-Matti, Lambrechts, Sandrina, Larson, Melissa C, Lasa, Adriana, Le, Nhu D, Leminen, Arto, Lester, Jenny, Li, Jingmei, Lindblom, Annika, Lissowska, Jolanta, Lu, Karen H, Lundvall, Lene, Mannermaa, Arto, McNeish, Iain, Modugno, Francesmary, Muranen, Taru A, Narod, Steven A, Nevanlinna, Heli, Pedersen, Inge Sokilde, Pike, Malcolm C, Plisiecka-Halasa, Joanna, Rebbeck, Timothy R, Reed, Malcolm W.R, Rodriguez, Gustavo C, Romero, Atocha, Rossing, Mary Anne, Rothstein, Joseph H, Rudolph, Anja, Salani, Ritu, Sawyer, Elinor J, Schmidt, Marjanka K, Schneeweiss, Andreas, Schoemaker, Minouk J, Schrauder, Michael G, Shrubsole, Martha, Sieh, Weiva, Sinilnikova, Olga M, Smeets, Dominiek, Tangen, Ingvild L, Terry, Kathryn L, Terry, Mary Beth, Thompson, Pamela J, Truong, Thérèse, Tyrer, Jonathan P, Vachon, Celine M, Van 't Veer, Laura J, van Altena, Anne M, Vitonis, Allison F, von Wachenfeldt, Anna, Walsh, Christine, Weitzel, Jeffrey N, Weltens, Caroline, Wentzensen, Nicolas, Rookus, Matti A
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2016
• Subjects: Basic Medicine; Breast cancer; Breast Neoplasms - enzymology; Breast Neoplasms - genetics; Cancer and Oncology; Cancer och onkologi; Carcinoma, Ovarian Epithelial; Clinical Medicine; Clinical outcome; Female; Genetic association; Hematology, Oncology and Palliative Medicine; Humans; Klinisk medicin; KRAS variant; Medical and Health Sciences; Medical Genetics; Medicin och hälsovetenskap; Medicinsk genetik; Medicinska och farmaceutiska grundvetenskaper; Neoplasms, Glandular and Epithelial - enzymology; Neoplasms, Glandular and Epithelial - genetics; Obstetrics and Gynecology; Ovarian cancer; Ovarian Neoplasms - enzymology; Ovarian Neoplasms - genetics; Proto-Oncogene Proteins p21(ras) - genetics; Clinical outcome; Breast cancer; KRAS variant; Genetic association; Ovarian cancer
• ISSN: 0090-8258; 1095-6859; 1095-6859
• DOI: 10.1016/j.ygyno.2015.04.034

Abstract Objective 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. Methods 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). Results 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. Conclusions 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.