Association between genetic polymorphisms in AURKA (rs2273535 and rs1047972) and breast cancer risk: a meta-analysis involving 37,221 subjects

BackgroundPublished 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.MethodsPubMed, Web of Knowledge and Embase were searched for relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to estimate the strength of associations. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were performed for allele contrast genetic model, homozygous genetic model, heterozygote genetic model, dominant model, and recessive model, respectively.ResultsA total of 13 studies (16,349 BC patients and 20,872 case-free controls) were involved in this meta-analysis. Meta-analysis showed that there was significant association between rs2273535 and BC risk in three genetic models in the overall population (A vs. T: OR = 1.08, 95% CI = 1.01-1.15, P = 0.02; AA vs. TT: OR = 1.36, 95% CI = 1.06-1.73, P < 0.00001; AA vs. TT + TA: OR = 1.15, 95% CI = 1.01-1.31, P = 0.04). In the subgroup analysis by ethnicity, the effects remained in Asians (allele contrast genetic model: OR = 1.12, 95% CI = 1.00-1.26, P = 0.04 and homozygote comparison: OR = 1.22, 95% CI = 1.06-1.41, P = 0.007). However, no genetic models reached statistical association in Cauasians. Rs1047972 polymorphism was associated with BC risk in the overall population based on homozygote comparison (AA vs. GG: OR = 0.81, 95% CI = 0.66-0.99, P = 0.04). When stratified by ethnicity, rs1047972 polymorphism had a decreased association with BC risk in Caucasians based on allele contrast genetic model, homozygote comparison, the dominant model and the recessive model. However, there was no association in any genetic model in Asians.ConclusionsThis meta-analysis suggests that AURKA rs2273535 polymorphism has an increased risk with BC, especially in Asians. However, rs1047972 polymorphism has a decreased BC risk in Caucasians. Further large scale multicenter epidemiological studies are warranted to confirm this finding.

[1]  Hiroki Nagase,et al.  Identification of Stk6/STK15 as a candidate low-penetrance tumor-susceptibility gene in mouse and human , 2003, Nature Genetics.

[2]  Chen-Yang Shen,et al.  Breast cancer risk associated with genotypic polymorphism of the mitosis‐regulating gene Aurora‐A/STK15/BTAK , 2005, International journal of cancer.

[3]  R. Vierkant,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 , 2007, Cancer Epidemiology Biomarkers & Prevention.

[4]  Constantin Sajdik,et al.  Genetic polymorphisms in AURKA and BRCA1 are associated with breast cancer susceptibility in a Chinese Han population , 2011, The Journal of pathology.

[5]  STK15 polymorphism and breast cancer risk in a population-based study. , 2004, Carcinogenesis.

[6]  P. Bugert,et al.  Aurora kinases A and B and familial breast cancer risk. , 2007, Cancer letters.

[7]  H. Saya,et al.  Aurora-A — A guardian of poles , 2005, Nature Reviews Cancer.

[8]  W. Lingle,et al.  Aurora A, centrosome structure, and the centrosome cycle , 2009, Environmental and molecular mutagenesis.

[9]  J. Labbé,et al.  APC/Fizzy‐Related targets Aurora‐A kinase for proteolysis , 2002, EMBO reports.

[10]  G. Schwartz,et al.  Aurora Kinases: New Targets for Cancer Therapy , 2006, Clinical Cancer Research.

[11]  Cheng Wu,et al.  Two nonsynonymous polymorphisms (F31I and V57I) of the STK15 gene and breast cancer risk: A meta-analysis based on 5966 cases and 7609 controls , 2013, The Journal of international medical research.

[12]  T. Hirao,et al.  Amplification/overexpression of Aurora-A in human gastric carcinoma: potential role in differentiated type gastric carcinogenesis. , 2004, Oncology reports.

[13]  Qing Jiang,et al.  Roles of Aurora Kinases in Mitosis and Tumorigenesis , 2007, Molecular Cancer Research.

[14]  J. Eyfjord,et al.  Breast cancer risk associated with AURKA 91T -->A polymorphism in relation to BRCA mutations. , 2007, Cancer letters.

[15]  A. Ashworth,et al.  Inconsistent association between the STK15 F31I genetic polymorphism and breast cancer risk. , 2006, Journal of the National Cancer Institute.

[16]  A. Balmain,et al.  Synergistic effects of STK15 gene polymorphisms and endogenous estrogen exposure in the risk of breast cancer. , 2004, Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology.

[17]  W. Tan,et al.  Functional Phe31Ile polymorphism in Aurora A and risk of breast carcinoma. , 2004, Carcinogenesis.

[18]  J. Kaprio,et al.  Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. , 2000, The New England journal of medicine.

[19]  J. Eyfjörd,et al.  Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome , 2011, Breast Cancer Research and Treatment.

[20]  R. Eils,et al.  Polymorphisms in the BRCA1 and ABCB1 genes modulate menopausal hormone therapy associated breast cancer risk in postmenopausal women , 2010, Breast Cancer Research and Treatment.

[21]  K. Czene,et al.  Attributable risks for familial breast cancer by proband status and morphology: A nationwide epidemiologic study from Sweden , 2002, International journal of cancer.

[22]  Pang-Kuo Lo,et al.  Epigenomics and breast cancer. , 2008, Pharmacogenomics.

[23]  Domenico Coppola,et al.  Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. , 2003, Clinical cancer research : an official journal of the American Association for Cancer Research.

[24]  A. Jemal,et al.  Cancer statistics, 2013 , 2013, CA: a cancer journal for clinicians.

[25]  Zhaoyang,et al.  Effects of interleukin-10 polymorphisms (rs1800896, rs1800871, and rs1800872) on breast cancer risk: evidence from an updated meta-analysis. , 2014 .

[26]  D. Medina,et al.  Centrosome amplification and overexpression of aurora A are early events in rat mammary carcinogenesis. , 2002, Cancer research.

[27]  David J. Hunter,et al.  Polymorphisms of the AURKA (STK15/Aurora Kinase) Gene and Breast Cancer Risk (United States) , 2006, Cancer Causes & Control.

[28]  S. Sen,et al.  Aurora-A/STK15/BTAK enhances chromosomal instability in bladder cancer cells. , 2004, International journal of oncology.

[29]  A. Balmain,et al.  Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types. , 2005, Carcinogenesis.