Couch Fergus J, Sinilnikova Olga, Vierkant Robert A, Pankratz V Shane, Fredericksen Zachary S, Stoppa-Lyonnet Dominique, Coupier Isabelle, Hughes David, Hardouin Agnès, Berthet Pascaline, Peock Susan, Cook Margaret, Baynes Caroline, Hodgson Shirley, Morrison Patrick J, Porteous Mary E, Jakubowska Anna, Lubinski Jan, Gronwald Jacek, Spurdle Amanda B, Schmutzler Rita, Versmold Beatrix, Engel Christoph, Meindl Alfons, Sutter Christian, Horst Jurgen, Schaefer Dieter, Offit Kenneth, Kirchhoff Tomas, Andrulis Irene L, Ilyushik Eduard, Glendon Gordon, Devilee Peter, Vreeswijk Maaike P G, Vasen Hans F A, Borg Ake, Backenhorn Katja, Struewing Jeffery P, Greene Mark H, Neuhausen Susan L, Rebbeck Timothy R, Nathanson Katherine, Domchek Susan, Wagner Theresa, Garber Judy E, Szabo Csilla, Zikan Michal, Foretova Lenka, Olson Janet E, Sellers Thomas A, Lindor Noralane, Nevanlinna Heli, Tommiska Johanna, Aittomaki Kristiina, Hamann Ute, Rashid Muhammad U, Torres Diana, Simard Jacques, Durocher Francine, Guenard Frederic, Lynch Henry T, Isaacs Claudine, Weitzel Jeffrey, Olopade Olufunmilayo I, Narod Steven, Daly Mary B, Godwin Andrew K, Tomlinson Gail, Easton Douglas F, Chenevix-Trench Georgia, Antoniou Antonis C
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA.
Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1416-21. doi: 10.1158/1055-9965.EPI-07-0129.
The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. 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. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
极光激酶A（AURKA）致癌基因与染色体异常分离、非整倍体及癌症易感性相关。与散发性乳腺肿瘤相比，在携带BRCA1和BRCA2基因突变的患者的肿瘤中，AURKA扩增的检出频率更高，这表明AURKA的过表达与BRCA1和BRCA2的失活在肿瘤发生发展过程中相互协作。此前的研究表明，AURKA基因中的F31I多态性在纯合状态下与乳腺癌风险相关。我们通过BRCA1/2修饰因子研究联盟，评估了AURKA基因F31I多态性是否会改变携带BRCA1和BRCA2基因突变患者患乳腺癌的风险。BRCA1/2修饰因子研究联盟的成立，是为了通过增加突变携带者的数量来提供足够的统计效力，以识别作为癌症风险修饰因子的多态性，并完善携带BRCA1和BRCA2基因突变患者的乳腺癌风险评估。对总共4935名携带BRCA1基因突变者、2241名携带BRCA2基因突变者以及11名同时携带BRCA1和BRCA2基因突变者进行了F31I基因分型。总体而言，在携带BRCA1和BRCA2基因突变者中，31I等位基因的纯合性与乳腺癌风险无显著相关性[风险比（HR）为0.91；95%置信区间（95%CI）为0.77 - 1.06]。同样，在携带BRCA1基因突变者（HR为0.90；95%CI为0.75 - 1.08）或携带BRCA2基因突变者（HR为0.93；95%CI为0.67 - 1.29）中，或者在评估双侧预防性卵巢切除术或BRCA1和BRCA2基因突变者的绝经状态的修饰作用时，均未发现显著相关性。总之，AURKA基因中的F31I多态性与携带BRCA1和BRCA2基因突变者患乳腺癌风险的改变无关。
