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

Weidhaas, Joanne B.; Slack, Frank J.; Miller, Nicola; Harris, Lyndsay N.; Tuck, David; Zhu, Yong; Zelterman, Daniel; Kerin, Michael J.; Paranjape, Trupti; Heneghan, Helen; Lindner, Robert; Keane, Florence K.; Dorairaj, Jemima; Geyda, Kimberly; Pelletier, Cory; Nallur, Sunitha

doi:10.1016/s1470-2045(11)70163-2

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“…However, in a subsequent study, the variant was reported to be associated with increased risk of ER/PR negative disease (80 cases, 470 controls), as well as with triple negative breast cancer diagnosed before age 52 (111 cases, 250 controls), regardless of BRCA1 mutation status [6]. The validity of these findings has been questioned given the very small sample sizes and the number of subgroups tested [16,17]. Another report found no association with sporadic or familial breast cancer risk (695 combined cases, 270 controls), but found that the variant was associated with ERBB2-positive and high grade disease, based on 153 cases who used post-menopausal hormone replacement therapy [18].…”

Section: Introductionmentioning

confidence: 99%

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

Hollestelle¹,

Baan²,

Berchuck³

et al. 2016

Gynecologic Oncology

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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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