Article

AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study.

Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA.
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.32). 08/2007; 16(7):1416-21. DOI: 10.1158/1055-9965.EPI-07-0129
Source: PubMed

ABSTRACT 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.

0 Followers
 · 
117 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The previous published data on the association between STK15 F31I and V57I polymorphisms and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and STK15 F31I (42,315 cases and 50,542 controls from 62 studies) and V57I polymorphisms (12,891 cases and 17,391 controls from 18 studies) in different inheritance models. Overall, significant association was observed between F31I and cancer risk when all the eligible studies were pooled into the meta-analysis (recessive model: OR = 1.14, 95 % CI = 1.06-1.24; AA vs. TT: OR = 1.12, 95 % CI = 1.02-1.24; A vs. T: OR = 1.05, 95 % CI = 1.01-1.09). In the further stratified and sensitivity analyses, for STK15 F31I, significantly increased breast cancer (recessive model: OR = 1.16, 95 % CI = 1.02-1.33; AA vs. TT: OR = 1.16, 95 % CI = 1.01-1.33) and ovarian cancer (dominant model: OR = 1.20, 95 % CI = 1.07-1.34; TA vs. TT: OR = 1.19, 95 % CI = 1.06-1.34; A vs. T: OR = 1.15, 95 % CI = 1.05-1.26) risk was found among Caucasians, and significantly decreased lung cancer risk was found among Caucasians (recessive model: OR = 0.65, 95 % CI = 0.49-0.87; AA vs. TT: OR = 0.65, 95 % CI = 0.49-0.88). For V57I polymorphism, significant decreased breast cancer risk was found among Caucasians (recessive model: OR = 0.76, 95 % CI = 0.61-0.95; AA vs. GG: OR = 0.75, 95 % CI = 0.60-0.94; A vs. G: OR = 0.92, 95 % CI = 0.86-0.98). In summary, this meta-analysis suggests that STK15 F31I polymorphism is associated with increased breast cancer and ovarian cancer risk among Caucasians, F31I polymorphism is associated with decreased lung cancer risk among Caucasians, and V57I polymorphism is associated with decreased breast cancer risk among Caucasians.
    Molecular Genetics and Genomics 08/2014; DOI:10.1007/s00438-014-0895-4 · 2.83 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Published data on the association between AURKA polymorphisms and breast cancer (BC) risk are inconclusive. This meta-analysis was performed to derive a more precise estimation on the relationship between AURKA polymorphisms (rs2273535 and rs1047972) and BC risk.
    Cancer Cell International 12/2014; 14(1):91. DOI:10.1186/s12935-014-0091-y · 1.99 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The rs2273535 polymorphism in the AURKA gene had proven to be associated with breast carcinoma susceptibility. Nevertheless, the results of different studies remain contradictory. A meta-analysis covering 28, 789 subjects from eleven different studies was here carried out in order to investigate the association in detail. The random effects model was used to analyze the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). A significant relationship between the rs2273535 polymorphism and breast tumors was found in an allelic genetic model (OR: 1.076, 95% CI: 1.004-1.153, p=0.040, Pheterogeneity=0.002). No significant association was detected in a homozygote model (OR: 1.186, 95% CI: 0.990-1.423, P=0.065, Pheterogeneity=0.002), a heterozygote model (OR: 1.016, 95% CI: 0.959-1.076, p=0.064, Pheterogeneity=0.000), a dominant genetic model (OR: 1.147, 95% CI: 0.992-1.325, p=0.217, Pheterogeneity=0.294) and a recessive genetic model (OR: 1.093, 95% CI: 0.878- 1.361, p=0.425, Pheterogeneity=0.707). A significant relationship between the rs2273535 polymorphism in the AURKA gene and breast tumor in Asian group was found in an allelic genetic model (OR: 1.124, 95% CI: 1.003-1.29, p=0.044, Pheterogeneity=0.034), a homozygote model (OR: 1.229, 95% CI: 1.038-1.455, p=0.016, Pheterogeneity=0.266) and a recessive genetic model (OR: 1.227, 95% CI: 1.001-1.504, p=0.049, Pheterogeneity=0.006). A significant association was thus observed between the rs2273535 polymorphism in the AURKA gene and breast cancer risk. Individuals with the rs2273535 polymorphism in the AURKA gene have a higher risk of breast cancer in Asian populations, but not in Caucasians.
    Asian Pacific journal of cancer prevention: APJCP 08/2014; 15(16):6709-14. DOI:10.7314/APJCP.2014.15.16.6709 · 1.50 Impact Factor

Full-text (2 Sources)

Download
25 Downloads
Available from
May 16, 2014