Common genetic polymorphisms of AURKA and prostate cancer risk

Feik, Elisabeth; Baierl, Andreas; Madersbacher, Stephan; Schatzl, Georg; Maj-Hes, Agnieszka; Berges, Richard; Micksche, M.; Gsur, Andrea

doi:10.1007/s10552-008-9227-5

Cited by 10 publications

(8 citation statements)

References 23 publications

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“…Although the Phe/Phe polymorphism is common and the Phe/Ile variant is more frequently found in tumour tissues, no correlation of either variant with the course or outcome of the disease could be found. Nevertheless, the AurkA polymorphism has been observed in many tumour types, e.g., oesophageal, breast, hepatocellular, and prostate cancer [17, 35-38]. Miao et al found a 44.2% frequency of the heterozygous allele in oesophageal tumour patients, the same range as found in the present study (49%).…”

Section: Discussionsupporting

confidence: 81%

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The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

et al. 2014

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ObjectivesThe aim of this study was to evaluate the efficiency of cetuximab-based anti-EGFR treatment and Aurora kinase A / B knockdown as a function of Aurora kinase polymorphism in HNSCC cell lines.Materials and methodsFirst, protein expression of Aurora kinase A / B and EGFR and Aurora kinase A polymorphism were studied in tumour samples.The survival and proliferation of Aurora kinase A homo- (Cal27) and heterozygous (HN) HNSCC cell lines was evaluated using a colony formation assay and a flow cytometric assay. Also, aneuploidy was determined. EGFR signalling pathway were visualised by western blotting.ResultsImmunohistochemistry revealed the overexpression of Aurora kinase A / B in HNSCC. The knockdown of each kinase caused a significant decrease in clonogenic survival, independent of Aurora kinase A polymorphism. In contrast, cetuximab treatment impaired clonogenic survival only in the Aurora kinase A-homozygous cell line (Cal27).ConclusionThis study provides in vitro evidence for the predictive value of Aurora kinase A polymorphism in the efficiency of cetuximab treatment. Resistance to cetuximab treatment can be overcome by simultaneous Aurora kinase A/B knockdown.

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Section: Discussionsupporting

confidence: 81%

“…In contrast, the frequency of the Ile/Ile polymorphism found in other tissues was clearly higher at 47.0% [17]. The prognostic value of either polymorphism, however, is unclear and remains controversial [17, 35-38]. …”

Section: Discussionmentioning

confidence: 99%

The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

et al. 2014

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“…The Taqman allelic discrimination method (Applied Biosystems, Darmstadt, Germany) was used to genotype rs8173 and rs2273535 [25]. For rs8173, the assay information was kindly provided by Dr. A. Gsur [26]. Detection was performed using an ABI PRISM 7900HT Sequence Detection system with SDS2.2 software (Applied Biosystems).…”

Section: Genotypingmentioning

confidence: 99%

Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome

Shi

Bevier

Grzybowska

et al. 2011

Breast Cancer Res Treat

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The 20q13 region is frequently amplified/overexpressed in breast tumours. However, the nature of this amplification/overexpression is unknown. Here, we investigated genetic variation in five 20q13 amplicon genes (MYBL2, AURKA, ZNF217, STK4 and PTPN1) and its impact on breast cancer (BC) susceptibility and clinical outcome. As a novel finding, four polymorphisms in STK4 (rs6017452, rs7271519) and AURKA (rs2273535, rs8173) associated with steroid hormone receptor status both in a Swedish population-based cohort of 783 BC cases and in a Polish familial/early onset cohort of 506 BC cases. In the joint analysis, the minor allele carriers of rs6017452 had more often hormone receptor positive tumours (OR 0.57, 95% CI 0.40-0.81), while homozygotes for the minor allele of rs7271519, rs2273535 and rs8173 had more often hormone receptor negative tumours (2.26, 1.30-3.39; 2.39, 1.14-5.01; 2.39, 1.19-4.80, respectively) than homozygotes for the common allele. BC-specific survival analysis of AURKA suggested that the Swedish carriers of the minor allele of rs16979877, rs2273535 and rs8173 might have a worse survival compared with the major homozygotes. The survival probabilities associated with the AURKA genotypes depended on the tumour phenotype. In the Swedish case-control study, associations with BC susceptibility were observed in a dominant model for three MYBL2 promoter polymorphisms (rs619289, P = 0.02; rs826943, P = 0.03 and rs826944, P = 0.02), two AURKA promoter polymorphisms (rs6064389, P = 0.04 and rs16979877, P = 0.02) and one 3'UTR polymorphism in ZNF217 (rs1056948, P = 0.01). In conclusion, our data confirmed the impact of the previously identified susceptibility locus and provided preliminary evidence for novel susceptibility variants in BC. We provided evidence for the first time that genetic variants at 20q13 may affect hormone receptor status in breast tumours and influence tumour aggressiveness and survival of the patients. Future studies are needed to confirm the prognostic value of our findings in the clinic.

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“…This analysis showed that the I31 allele increases the risk ofmultiple cancer types and confirmed the I31 allele is a low‐penetrance cancer susceptibility allele. Nonetheless, it should be noted that some studies, including breast cancer, prostate cancer, gastric cancer and mantle cell lymphoma, have found no association with Aurora A I31 allele [24–26,29,30,32].…”

Section: Discussionmentioning

confidence: 99%

“…Several case-control studies have investigated the association between F31I polymorphism of Aurora A gene and cancer risk [21][22][23][24][25][26][27][28][29][30][31][32]. However, the results have not been consistent, although a meta-analysis of 15 case-control studies concerning Aurora A F31I polymorphism showed that carriers of the I31 allele had an increased risk of multiple cancers [20].…”

Section: Introductionmentioning

confidence: 99%

Relationship between functional polymorphism in the Aurora A gene and susceptibility of hepatocellular carcinoma

Akkız¹,

Bayram

Bekar³

et al. 2009

Journal of Viral Hepatitis

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Aurora A is considered a potential cancer susceptibility gene owing to overexpression or amplification of Aurora A gene that causes centrosome dysfunction, chromosome instability, tumourigenic transformation and checkpoint abnormalities. Functional coding region polymorphism F31I in the Aurora A gene has recently been shown to be associated with several human cancers, but its association with hepatocellular carcinoma (HCC) has yet to be investigated. Genetic polymorphism of Aurora A was investigated in 128 confirmed subjects with HCC and 128 cancer-free control subjects matched on age, gender, smoking and alcohol consumption by using a polymerase chain reaction-restriction fragment length polymorphism assay. Allele and genotype associations of Aurora A F31I polymorphism with HCC susceptibility were observed in comparisons between the patient and control samples (respectively; P = 0.005, P = 0.012). The proportion of the genotypes containing I31 allele in patients with HCC (39.8%) was significantly higher than that in patients without HCC (22.7%) (P = 0.003). The distribution F31I genotype was significantly associated with increased risk of HCC (P = 0.003, odds ratio = 2.26, 95% confidence interval = 1.31-3.90 for FI + II genotypes vs FF genotype). Our results suggest for the first time that the Aurora A F31I polymorphism may be a genetic susceptibility factor for HCC.

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Common genetic polymorphisms of AURKA and prostate cancer risk

Abstract: The two investigated SNPs in AURKA were not found to be associated with prostate cancer risk. Other common SNPs of AURKA should be investigated in further studies because of its location on a prostate cancer susceptibility locus.

Cited by 10 publications

References 23 publications

The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

The response of head and neck squamous cell carcinoma to cetuximab treatment depends on Aurora kinase A polymorphism

Single nucleotide polymorphisms in the 20q13 amplicon genes in relation to breast cancer risk and clinical outcome

Relationship between functional polymorphism in the Aurora A gene and susceptibility of hepatocellular carcinoma

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