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AURKA and Breast Cancer in BRCA1/2 Mutation Carriers

Department of Medicine, University of Iceland, Reykjavik, Iceland

To the Editors: A recent article reported, "the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer found in 3,884 breast cancer BRCA1 and BRCA2 carrier cases compared to unaffected BRCA1/2 mutation carriers" (1). This agrees with our previously published results where no association of increased breast cancer risk was found in 107 BRCA1 and BRCA2 breast cancer carrier cases compared with 653 unaffected wild-type BRCA1/2 controls (2), which Couch et al. did not cite. We also found strong association with homozygous 31I in 652 sporadic breast cancer cases compared with unaffected controls. In addition, we compared the F31I polymorphism in the 107 BRCA1/2-mutated breast cancer cases with 40 unaffected BRCA2 mutation carriers. We found that the unaffected BRCA2 mutation carriers had clearly higher 31I allele frequency of 27.5% compared with 21.0% in BRCA1/2 breast cancer cases, which indicates that the 31I isoform might be protecting against breast tumor development in BRCA2 mutation carriers. Our results, and those of Couch et al., about BRCA1/2 mutation carrier cases agree with recent studies on familial or high-risk breast cancer cases that did not find association between the F31I polymorphism and breast cancer risk. On the other hand, increased sporadic breast cancer risk is associated with the F31I polymorphism as discussed before (2). It is therefore clearly important when looking for low-penetrance cancer susceptibility genes to acknowledge the influence of major cancer genes, such as BRCA1 and BRCA2.

Couch et al. (1) state both in abstract and introduction, "amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression." No citations were given for this statement and, to our knowledge, there are no published data showing association between AURKA amplification and BRCA1 inactivation. On the other hand, we recently reported a strong association between AURKA (Aurora-A) amplification and BRCA2 mutation in breast tumors (3). In this study, we analyzed 61 breast tumor tissue sections for AURKA amplification by fluorescence in situ hybridization, where 20 had BRCA2 mutation. Other studies based on comparative genomic hybridization of BRCA1/2-mutated breast tumors agree with our results where chromosome region 20q13, the location of the AURKA gene, is more often amplified in BRCA2-mutated tumors compared with sporadic and BRCA1-mutated breast tumors (4-6).

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1. Couch FJ, Sinilnikova O, Vierkant RA, et al. AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study. Cancer Epidemiol Biomarkers Prev 2007;16:1416–21.[Abstract/Free Full Text]
2. Vidarsdottir L, Bodvarsdottir SK, Hilmarsdottir H, Tryggvadottir L, Eyfjord JE. Breast cancer risk associated with AURKA 91TA polymorphism in relation to BRCA mutations. Cancer Lett 2007;250:206–12.[Medline]
3. Bodvarsdottir SK, Hilmarsdottir H, Birgisdottir V, Steinarsdottir M, Jonasson JG, Eyfjord JE. Aurora-A amplification associated with BRCA2 mutation in breast tumours. Cancer Lett 2007;248:96–102.[Medline]
4. Tirkkonen M, Johannsson O, Agnarsson BA, et al. Distinct somatic genetic changes associated with tumor progression in carriers of BRCA1 and BRCA2 germ-line mutations. Cancer Res 1997;57:1222–7.[Abstract/Free Full Text]
5. van Beers EH, van Welsem T, Wessels LF, et al. Comparative genomic hybridization profiles in human BRCA1 and BRCA2 breast tumors highlight differential sets of genomic aberrations. Cancer Res 2005;65:822–7.[Abstract/Free Full Text]
6. Jonsson G, Naylor TL, Vallon-Christersson J, et al. Distinct genomic profiles in hereditary breast tumors identified by array-based comparative genomic hybridization. Cancer Res 2005;65:7612–21.[Abstract/Free Full Text]

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