The University of Southampton
University of Southampton Institutional Repository

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

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
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.
KRAS variant, breast cancer, ovarian cancer, genetic association, clinical outcome
0090-8258
Hollestelle, Antoinette
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van der Baan, Frederieke H.
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Berchuck, Andrew
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van Rensburg, Elizabeth J.
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Vergote, Ignace
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Verhoef, Senno
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Vierkant, Robert A.
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Vijai, Joseph
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von Wachenfeldt, Anna
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Wang, Qin
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Wang-Gohrke, Shan
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Wappenschmidt, Barbara
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Weischer, Maren
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Weitzel, Jeffrey N.
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Zheng, Wei
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Ziogas, Argyrios
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Hollestelle, Antoinette, van der Baan, Frederieke H. and Berchuck, Andrew et al. (2015) No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecologic Oncology. (doi:10.1016/j.ygyno.2015.04.034). (PMID:25940428)

Record type: Article

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.

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More information

Accepted/In Press date: 19 April 2015
e-pub ahead of print date: 2 May 2015
Keywords: KRAS variant, breast cancer, ovarian cancer, genetic association, clinical outcome
Organisations: Cancer Sciences

Identifiers

Local EPrints ID: 380279
URI: http://eprints.soton.ac.uk/id/eprint/380279
ISSN: 0090-8258
PURE UUID: 31564bea-8c8f-4ae4-8ea9-68956600db50
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 11 Aug 2015 14:06
Last modified: 15 Mar 2024 02:40

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Author: Antoinette Hollestelle
Author: Frederieke H. van der Baan
Author: Andrew Berchuck
Author: Sharon E. Johnatty
Author: Katja K. Aben
Author: Bjarni A. Agnarsson
Author: Kristiina Aittomäki
Author: Elisa Alducci
Author: Irene L. Andrulis
Author: Hoda Anton-Culver
Author: Natalia N. Antonenkova
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Author: Carmel Apicella
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Author: Brita Arver
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Author: Rosemary Balleine
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Author: Daniel Barrowdale
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Author: Raanan Berger
Author: Benoit Beuselinck
Author: Maria Bisogna
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