KRAS变异体rs61764370对卵巢癌或乳腺癌无临床应用价值。
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.
作者信息
Hollestelle Antoinette, van der Baan Frederieke H, Berchuck Andrew, Johnatty Sharon E, Aben Katja K, Agnarsson Bjarni A, Aittomäki Kristiina, Alducci Elisa, Andrulis Irene L, Anton-Culver Hoda, Antonenkova Natalia N, Antoniou Antonis C, Apicella Carmel, Arndt Volker, Arnold Norbert, Arun Banu K, Arver Brita, Ashworth Alan, Baglietto Laura, Balleine Rosemary, Bandera Elisa V, Barrowdale Daniel, Bean Yukie T, Beckmann Lars, Beckmann Matthias W, Benitez Javier, Berger Andreas, Berger Raanan, Beuselinck Benoit, Bisogna Maria, Bjorge Line, Blomqvist Carl, Bogdanova Natalia V, Bojesen Anders, Bojesen Stig E, Bolla Manjeet K, Bonanni Bernardo, Brand Judith S, Brauch Hiltrud, Brenner Hermann, Brinton Louise, Brooks-Wilson Angela, Bruinsma Fiona, Brunet Joan, Brüning Thomas, Budzilowska Agnieszka, Bunker Clareann H, Burwinkel Barbara, Butzow Ralf, Buys Saundra S, Caligo Maria A, Campbell Ian, Carter Jonathan, Chang-Claude Jenny, Chanock Stephen J, Claes Kathleen B M, Collée J Margriet, Cook Linda S, Couch Fergus J, Cox Angela, Cramer Daniel, Cross Simon S, Cunningham Julie M, Cybulski Cezary, Czene Kamila, Damiola Francesca, Dansonka-Mieszkowska Agnieszka, Darabi Hatef, de la Hoya Miguel, deFazio Anna, Dennis Joseph, Devilee Peter, Dicks Ed M, Diez Orland, Doherty Jennifer A, Domchek Susan M, Dorfling Cecilia M, Dörk Thilo, Silva Isabel Dos Santos, du Bois Andreas, Dumont Martine, Dunning Alison M, Duran Mercedes, Easton Douglas F, Eccles Diana, Edwards Robert P, Ehrencrona Hans, Ejlertsen Bent, Ekici Arif B, Ellis Steve D, Engel Christoph, Eriksson Mikael, Fasching Peter A, Feliubadalo Lidia, Figueroa Jonine, Flesch-Janys Dieter, Fletcher Olivia, Fontaine Annette, Fortuzzi Stefano, Fostira Florentia, Fridley Brooke L, Friebel Tara, Friedman Eitan, Friel Grace, Frost Debra, Garber Judy, García-Closas Montserrat, Gayther Simon A, Gentry-Maharaj Aleksandra, Gerdes Anne-Marie, Giles Graham G, Glasspool Rosalind, Glendon Gord, Godwin Andrew K, Goodman Marc T, Gore Martin, Greene Mark H, Grip Mervi, Gronwald Jacek, Gschwantler Kaulich Daphne, Guénel Pascal, Guzman Starr R, Haeberle Lothar, Haiman Christopher A, Hall Per, Halverson Sandra L, Hamann Ute, Hansen Thomas V O, Harter Philipp, Hartikainen Jaana M, Healey Sue, Hein Alexander, Heitz Florian, Henderson Brian E, Herzog Josef, T Hildebrandt Michelle A, Høgdall Claus K, Høgdall Estrid, Hogervorst Frans B L, Hopper John L, Humphreys Keith, Huzarski Tomasz, Imyanitov Evgeny N, Isaacs Claudine, Jakubowska Anna, Janavicius Ramunas, Jaworska Katarzyna, Jensen Allan, Jensen Uffe Birk, Johnson Nichola, Jukkola-Vuorinen Arja, Kabisch Maria, Karlan Beth Y, Kataja Vesa, Kauff Noah, Kelemen Linda E, Kerin Michael J, Kiemeney Lambertus A, Kjaer Susanne K, Knight Julia A, Knol-Bout Jacoba P, Konstantopoulou Irene, Kosma Veli-Matti, Krakstad Camilla, Kristensen Vessela, Kuchenbaecker Karoline B, Kupryjanczyk Jolanta, Laitman Yael, Lambrechts Diether, Lambrechts Sandrina, Larson Melissa C, Lasa Adriana, Laurent-Puig Pierre, Lazaro Conxi, Le Nhu D, Le Marchand Loic, Leminen Arto, Lester Jenny, Levine Douglas A, Li Jingmei, Liang Dong, Lindblom Annika, Lindor Noralane, Lissowska Jolanta, Long Jirong, Lu Karen H, Lubinski Jan, Lundvall Lene, Lurie Galina, Mai Phuong L, Mannermaa Arto, Margolin Sara, Mariette Frederique, Marme Frederik, Martens John W M, Massuger Leon F A G, Maugard Christine, Mazoyer Sylvie, McGuffog Lesley, McGuire Valerie, McLean Catriona, McNeish Iain, Meindl Alfons, Menegaux Florence, Menéndez Primitiva, Menkiszak Janusz, Menon Usha, Mensenkamp Arjen R, Miller Nicola, Milne Roger L, Modugno Francesmary, Montagna Marco, Moysich Kirsten B, Müller Heiko, Mulligan Anna Marie, Muranen Taru A, Narod Steven A, Nathanson Katherine L, Ness Roberta B, Neuhausen Susan L, Nevanlinna Heli, Neven Patrick, Nielsen Finn C, Nielsen Sune F, Nordestgaard Børge G, Nussbaum Robert L, Odunsi Kunle, Offit Kenneth, Olah Edith, Olopade Olufunmilayo I, Olson Janet E, Olson Sara H, Oosterwijk Jan C, Orlow Irene, Orr Nick, Orsulic Sandra, Osorio Ana, Ottini Laura, Paul James, Pearce Celeste L, Pedersen Inge Sokilde, Peissel Bernard, Pejovic Tanja, Pelttari Liisa M, Perkins Jo, Permuth-Wey Jenny, Peterlongo Paolo, Peto Julian, Phelan Catherine M, Phillips Kelly-Anne, Piedmonte Marion, Pike Malcolm C, Platte Radka, Plisiecka-Halasa Joanna, Poole Elizabeth M, Poppe Bruce, Pylkäs Katri, Radice Paolo, Ramus Susan J, Rebbeck Timothy R, Reed Malcolm W R, Rennert Gad, Risch Harvey A, Robson Mark, Rodriguez Gustavo C, Romero Atocha, Rossing Mary Anne, Rothstein Joseph H, Rudolph Anja, Runnebaum Ingo, Salani Ritu, Salvesen Helga B, Sawyer Elinor J, Schildkraut Joellen M, Schmidt Marjanka K, Schmutzler Rita K, Schneeweiss Andreas, Schoemaker Minouk J, Schrauder Michael G, Schumacher Fredrick, Schwaab Ira, Scuvera Giulietta, Sellers Thomas A, Severi Gianluca, Seynaeve Caroline M, Shah Mitul, Shrubsole Martha, Siddiqui Nadeem, Sieh Weiva, Simard Jacques, Singer Christian F, Sinilnikova Olga M, Smeets Dominiek, Sohn Christof, Soller Maria, Song Honglin, Soucy Penny, Southey Melissa C, Stegmaier Christa, Stoppa-Lyonnet Dominique, Sucheston Lara, Swerdlow Anthony, Tangen Ingvild L, Tea Muy-Kheng, Teixeira Manuel R, Terry Kathryn L, Terry Mary Beth, Thomassen Mads, Thompson Pamela J, Tihomirova Laima, Tischkowitz Marc, Toland Amanda Ewart, Tollenaar Rob A E M, Tomlinson Ian, Torres Diana, Truong Thérèse, Tsimiklis Helen, Tung Nadine, Tworoger Shelley S, Tyrer Jonathan P, Vachon Celine M, Van 't Veer Laura J, van Altena Anne M, Van Asperen C J, van den Berg David, van den Ouweland Ans M W, van Doorn Helena C, Van Nieuwenhuysen Els, van Rensburg Elizabeth J, Vergote Ignace, Verhoef Senno, Vierkant Robert A, Vijai Joseph, Vitonis Allison F, von Wachenfeldt Anna, Walsh Christine, Wang Qin, Wang-Gohrke Shan, Wappenschmidt Barbara, Weischer Maren, Weitzel Jeffrey N, Weltens Caroline, Wentzensen Nicolas, Whittemore Alice S, Wilkens Lynne R, Winqvist Robert, Wu Anna H, Wu Xifeng, Yang Hannah P, Zaffaroni Daniela, Pilar Zamora M, Zheng Wei, Ziogas Argyrios, Chenevix-Trench Georgia, Pharoah Paul D P, Rookus Matti A, Hooning Maartje J, Goode Ellen L
机构信息
Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
Department of Epidemiology, Netherlands Cancer Institute, Amsterdam, The Netherlands.
出版信息
Gynecol Oncol. 2016 May;141(2):386-401. doi: 10.1016/j.ygyno.2015.04.034. Epub 2015 May 2.
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.
目的
基于与卵巢癌和乳腺癌风险增加以及生存时间的关联提示，针对位于KRAS 3'UTR微小RNA结合位点的遗传性变异rs61764370的临床基因检测已商业化。然而，先前强调特定亚组的研究规模相对较小。因此，我们全面评估了与rs61764370相关的卵巢癌和乳腺癌风险以及临床结局。
方法
对卵巢癌协会联盟（15357例卵巢癌患者；30816例对照）、乳腺癌协会联盟（33530例乳腺癌患者；37640例对照）以及BRCA1和BRCA2修饰因子联盟（14765例BRCA1突变携带者和7904例BRCA2突变携带者）纳入的140012名女性进行集中基因分型和分析。
结果
我们发现该变异与卵巢癌风险（OR = 0.99，95%CI 0.94 - 1.04，p = 0.74）或乳腺癌风险（OR = 0.98，95%CI 0.94 - 1.01，p = 0.19）均无关联，并且在突变携带者中结果一致（BRCA1，卵巢癌HR = 1.09，95%CI 0.97 - 1.23，p = 0.14，乳腺癌HR = 1.04，95%CI 0.97 - 1.12，p = 0.27；BRCA2，卵巢癌HR = 0.89，95%CI 0.71 - 1.13，p = 0.34，乳腺癌HR = 1.06，95%CI 0.94 - 1.19，p = 0.35）。在与卵巢癌（HR = 0.94，95%CI 0.83 - 1.07，p = 0.38）、乳腺癌（HR = 0.96，95%CI 0.87 - 1.06，p = 0.38）以及所有其他先前报道的关联方面，也得到了阴性结果。
结论
rs61764370与卵巢癌或乳腺癌风险以及这些癌症患者的临床结局均无关联。因此，对该变异进行基因分型对于这些癌症的预测或管理没有临床实用价值。
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