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

Antoinette Hollestelle; Frederieke H van der Baan; Andrew Berchuck; Sharon E Johnatty; Katja K Aben; Bjarni A Agnarsson; Kristiina Aittomäki; Elisa Alducci; Irene L Andrulis; Hoda Anton-Culver; Natalia N Antonenkova; Antonis C Antoniou; Carmel Apicella; Volker Arndt; Norbert Arnold; Banu K Arun; Brita Arver; Alan Ashworth; Laura Baglietto; Rosemary Balleine; Elisa V Bandera; Daniel Barrowdale; Yukie T Bean; Lars Beckmann; Matthias W Beckmann; Javier Benitez; Andreas Berger; Raanan Berger; Benoit Beuselinck; Maria Bisogna; Line Bjorge; Carl Blomqvist; Natalia V Bogdanova; Anders Bojesen; Stig E Bojesen; Manjeet K Bolla; Bernardo Bonanni; Judith S Brand; Hiltrud Brauch; Hermann Brenner; Louise Brinton; Angela Brooks-Wilson; Fiona Bruinsma; Joan Brunet; Anne-Marie Gerdes; Claus K Høgdall; Estrid Høgdall; Susanne K Kjaer; Finn C Nielsen; Børge G Nordestgaard; Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2

doi:10.1016/j.ygyno.2015.04.034

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

Antoinette Hollestelle, Frederieke H van der Baan, Andrew Berchuck, Sharon E Johnatty, Katja K Aben, Bjarni A Agnarsson, Kristiina Aittomäki, Elisa Alducci, Irene L Andrulis, Hoda Anton-Culver, Natalia N Antonenkova, Antonis C Antoniou, Carmel Apicella, Volker Arndt, Norbert Arnold, Banu K Arun, Brita Arver, Alan Ashworth, Laura Baglietto, Rosemary BalleineElisa V Bandera, Daniel Barrowdale, Yukie T Bean, Lars Beckmann, Matthias W Beckmann, Javier Benitez, Andreas Berger, Raanan Berger, Benoit Beuselinck, Maria Bisogna, Line Bjorge, Carl Blomqvist, Natalia V Bogdanova, Anders Bojesen, Stig E Bojesen, Manjeet K Bolla, Bernardo Bonanni, Judith S Brand, Hiltrud Brauch, Hermann Brenner, Louise Brinton, Angela Brooks-Wilson, Fiona Bruinsma, Joan Brunet, Anne-Marie Gerdes, Claus K Høgdall, Estrid Høgdall, Susanne K Kjaer, Finn C Nielsen, Børge G Nordestgaard, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2

Department of Clinical Medicine

10 Citations (Scopus)

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.

Original language	English
Journal	Gynecologic Oncology
Volume	141
Issue number	2
Pages (from-to)	386–401
ISSN	0090-8258
DOIs	https://doi.org/10.1016/j.ygyno.2015.04.034
Publication status	Published - 1 May 2016

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10.1016/j.ygyno.2015.04.034

https://helda.helsinki.fi/bitstream/10138/223960/1/1_s2.0_S009082581500863X_main.pdf

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Hollestelle, A., van der Baan, F. H., Berchuck, A., Johnatty, S. E., Aben, K. K., Agnarsson, B. A., Aittomäki, K., Alducci, E., Andrulis, I. L., Anton-Culver, H., Antonenkova, N. N., Antoniou, A. C., Apicella, C., Arndt, V., Arnold, N., Arun, B. K., Arver, B., Ashworth, A., Baglietto, L., ... Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2 (2016). No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology, 141(2), 386–401. https://doi.org/10.1016/j.ygyno.2015.04.034

Hollestelle, A, van der Baan, FH, Berchuck, A, Johnatty, SE, Aben, KK, Agnarsson, BA, Aittomäki, K, Alducci, E, Andrulis, IL, Anton-Culver, H, Antonenkova, NN, Antoniou, AC, Apicella, C, Arndt, V, Arnold, N, Arun, BK, Arver, B, Ashworth, A, Baglietto, L, Balleine, R, Bandera, EV, Barrowdale, D, Bean, YT, Beckmann, L, Beckmann, MW, Benitez, J, Berger, A, Berger, R, Beuselinck, B, Bisogna, M, Bjorge, L, Blomqvist, C, Bogdanova, NV, Bojesen, A, Bojesen, SE, Bolla, MK, Bonanni, B, Brand, JS, Brauch, H, Brenner, H, Brinton, L, Brooks-Wilson, A, Bruinsma, F, Brunet, J, Gerdes, A-M , Høgdall, CK , Høgdall, E , Kjaer, SK , Nielsen, FC , Nordestgaard, BG & Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2 2016, 'No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer', Gynecologic Oncology, vol. 141, no. 2, pp. 386–401. https://doi.org/10.1016/j.ygyno.2015.04.034

@article{4b1a9a585685494f8e53f6b500040232,

title = "No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer",

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.",

author = "Antoinette Hollestelle and {van der Baan}, {Frederieke H} and Andrew Berchuck and Johnatty, {Sharon E} and Aben, {Katja K} and Agnarsson, {Bjarni A} and Kristiina Aittom{\"a}ki and Elisa Alducci and Andrulis, {Irene L} and Hoda Anton-Culver and Antonenkova, {Natalia N} and Antoniou, {Antonis C} and Carmel Apicella and Volker Arndt and Norbert Arnold and Arun, {Banu K} and Brita Arver and Alan Ashworth and Laura Baglietto and Rosemary Balleine and Bandera, {Elisa V} and Daniel Barrowdale and Bean, {Yukie T} and Lars Beckmann and Beckmann, {Matthias W} and Javier Benitez and Andreas Berger and Raanan Berger and Benoit Beuselinck and Maria Bisogna and Line Bjorge and Carl Blomqvist and Bogdanova, {Natalia V} and Anders Bojesen and Bojesen, {Stig E} and Bolla, {Manjeet K} and Bernardo Bonanni and Brand, {Judith S} and Hiltrud Brauch and Hermann Brenner and Louise Brinton and Angela Brooks-Wilson and Fiona Bruinsma and Joan Brunet and Anne-Marie Gerdes and H{\o}gdall, {Claus K} and Estrid H{\o}gdall and Kjaer, {Susanne K} and Nielsen, {Finn C} and Nordestgaard, {B{\o}rge G} and {Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2}",

note = "Copyright {\textcopyright} 2015. Published by Elsevier Inc.",

year = "2016",

month = may,

day = "1",

doi = "10.1016/j.ygyno.2015.04.034",

language = "English",

volume = "141",

pages = "386–401",

journal = "Gynecologic Oncology",

issn = "0090-8258",

publisher = "Academic Press",

number = "2",

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TY - JOUR

T1 - No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer

AU - Hollestelle, Antoinette

AU - van der Baan, Frederieke H

AU - Berchuck, Andrew

AU - Johnatty, Sharon E

AU - Aben, Katja K

AU - Agnarsson, Bjarni A

AU - Aittomäki, Kristiina

AU - Alducci, Elisa

AU - Andrulis, Irene L

AU - Anton-Culver, Hoda

AU - Antonenkova, Natalia N

AU - Antoniou, Antonis C

AU - Apicella, Carmel

AU - Arndt, Volker

AU - Arnold, Norbert

AU - Arun, Banu K

AU - Arver, Brita

AU - Ashworth, Alan

AU - Baglietto, Laura

AU - Balleine, Rosemary

AU - Bandera, Elisa V

AU - Barrowdale, Daniel

AU - Bean, Yukie T

AU - Beckmann, Lars

AU - Beckmann, Matthias W

AU - Benitez, Javier

AU - Berger, Andreas

AU - Berger, Raanan

AU - Beuselinck, Benoit

AU - Bisogna, Maria

AU - Bjorge, Line

AU - Blomqvist, Carl

AU - Bogdanova, Natalia V

AU - Bojesen, Anders

AU - Bojesen, Stig E

AU - Bolla, Manjeet K

AU - Bonanni, Bernardo

AU - Brand, Judith S

AU - Brauch, Hiltrud

AU - Brenner, Hermann

AU - Brinton, Louise

AU - Brooks-Wilson, Angela

AU - Bruinsma, Fiona

AU - Brunet, Joan

AU - Gerdes, Anne-Marie

AU - Høgdall, Claus K

AU - Høgdall, Estrid

AU - Kjaer, Susanne K

AU - Nielsen, Finn C

AU - Nordestgaard, Børge G

AU - Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2

PY - 2016/5/1

Y1 - 2016/5/1

N2 - 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.

AB - 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.

U2 - 10.1016/j.ygyno.2015.04.034

DO - 10.1016/j.ygyno.2015.04.034

M3 - Review

C2 - 25940428

SN - 0090-8258

VL - 141

SP - 386

EP - 401

JO - Gynecologic Oncology

JF - Gynecologic Oncology

IS - 2

ER -

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

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