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https://ir.csmu.edu.tw:8080/ir/handle/310902500/19407
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| Title: | Combined effect of genetic polymorphisms of AURKA and environmental factors on oral cancer development in Taiwan |
| Authors: | Chou, Chia-Hsuan
Chou, Ying-Erh
Chuang, Chun-Yi
Yang, Shun-Fa
Lin, Chiao-Wen |
| Contributors: | 中山醫學大學口腔醫學研究所 |
| Date: | 2017-02-02 |
| Issue Date: | 2018-10-17T07:47:55Z (UTC)
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| Abstract: | Background
Oral squamous cell carcinoma (OSCC) is the sixth and fourth most common cause of cancer death in men worldwide and in Taiwan, respectively. AURKA, which encodes a centrosome-related serine/threonine kinase, is frequently amplified and overexpressed in many human cancers, particularly advanced OSCC. We conducted a hospital-based case-control study to estimate AURKA single-nucleotide polymorphisms (SNPs) and environmental risk factors to determine OSCC susceptibility and clinicopathological characteristics.
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Methodology/Principal findings
We enrolled a total of 876 OSCC patients and 1200 controls. Four SNPs of AURKA, namely rs1047972, rs2273535, rs2064863, and rs6024836, were analyzed using real-time polymerase chain reaction (PCR). Among the 1420 smokers, the AURKA polymorphism carriers with the betel nut chewing habit had a higher risk of oral cancer than AURKA wild-type (WT) carriers without the betel nut chewing habit. Patients with the AURKA rs2064863 gene had a 1.365-fold higher risk of stage III or IV OSCC (95% confidence interval [CI] 1.029–1.811) than those with the rs2064863 WT gene. Furthermore, carriers of the AURKA rs1047972/rs2273535/rs2064863 C-A-T haplotype had a 1.736-fold (95% CI 1.110–2.715) higher risk of OSCC than controls (C-T-T, the most common haplotype). Among patients with the betel quid chewing habit, carriers of other haplotypes (C-T-T, C-A-G, T-A-T, T-A-G, T-T-T, and C-T-G) had a 12.857-fold (95% CI 10.731–15.404) increased risk, and carriers of the C-A-T haplotype had the highest risk (AOR: 31.120; 95% CI 13.864–69.850) of OSCC, compared with those without the betel quid chewing who harbored other haplotypes.
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Conclusions
In conclusion, betel nut chewing combined with the AURKA C-A-T haplotypes lead to a high risk of OSCC. These findings reveal a novel genetic-environmental predisposition for oral tumorigenesis.
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Introduction
More than 90% of all head and neck malignant tumors occur in oral squamous cell carcinoma (OSCC) patients [1]. OSCC is the sixth and fourth most common cause of cancer death in men worldwide and in Taiwan, respectively [2]. Patients usually seek treatment only at the advanced stage of OSCC, resulting in a relatively low 5-year survival rate [3]. Both genetic factors and carcinogen-exposure behaviors (for example: betel nut chewing, alcohol consumption, and tobacco) regulate OSCC development [4, 5]. Moreover, our previous studies have demonstrated that genetic polymorphism combined with betel nut carcinogens may increase susceptibility to OSCC [6–12]. The results illustrate the importance of single-nucleotide polymorphisms (SNPs) for predicting risk or prognosis of OSCC.
AURKA, also known as Aurora Kinase A, encodes a centrosome-related serine/threonine kinase and is frequently amplified and overexpressed in many human cancers [13–15], particularly advanced OSCC [16]. Moreover, this gene has been identified as a definite low-penetrance tumor susceptibility gene [17]. The high expression of AURKA might be induced by centrosome amplification, aberrant chromosome segregation, aneuploidy, and malignant transformation [18–20], thus mediating the molecular mechanisms underlying carcinogenesis. The genetic associations of AURKA with several conditions have been documented. Lee et al demonstrated that the AA genotype of AURKA rs2273535 T>A was associated with an increased risk of oral cancer [21]. Dai et al reported that Caucasians harboring AURKA rs1047972 T>C had a reduced breast cancer risk [22]. However, few genetic variants of AURKA have been associated with OSCC.
In this case-control study, we investigated the relationship of four AURKA polymorphisms—namely rs1047972, rs2273535, rs2064863, and rs6024836—with OSCC susceptibility in Taiwanese male patients with OSCC. |
| URI: | https://ir.csmu.edu.tw:8080/ir/handle/310902500/19407 |
| Relation: | PLoS One. 2017; 12(2): e0171583 |
| Appears in Collections: | [口腔醫學研究所] 期刊論文
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