Association between the STK15 F31I Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 43,626 Subjects

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Abstract

The association between the Serine/threonine kinase 15 (STK15) F31I polymorphism (rs2273535) and cancer susceptibility remains controversial. To further investigate this potential relationship, we conducted a comprehensive meta-analysis of 27 published studies involving a total of 19,267 multiple cancer cases and 24,359 controls. Our results indicate statistical evidence of an association between the STK15 F31I polymorphism and the increased risk of overall cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T. In a stratified analysis by cancer type, there was an increased risk of breast cancer in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA, and A vs. T, as well as esophageal cancer in two genetic models: AA vs. TA+TT and AA vs. TA. In a stratified analysis by ethnicity, there was a significant increase in cancer risk among Asians, but not Caucasians, in four genetic models: AA vs. TA+TT, AA vs. TT, AA vs. TA and A vs. T. In addition, a stratified analysis by ethnicity in the breast cancer subgroup revealed a significant increase in cancer risk among Asians in two genetic models: AA vs. TA+TT and AA vs. TT, as well as among Caucasians in one genetic model: AA vs. TA. In summary, this meta-analysis demonstrates that the STK15 F31I polymorphism may be a risk factor for cancer.

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Most cited references 38

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Tomotoshi Marumoto, Dongwei Zhang, Hideyuki Saya (2005)

The three human homologues of Aurora kinases (A, B and C) are essential for proper execution of various mitotic events and are important for maintaining genomic integrity. Aurora-A is mainly localized at spindle poles and the mitotic spindle during mitosis, where it regulates the functions of centrosomes, spindles and kinetochores required for proper mitotic progression. Recent studies have revealed that Aurora-A is frequently overexpressed in various cancer cells, indicating its involvement in tumorigenesis. What are the normal physiological roles of Aurora-A, how are these regulated and how might the enzyme function during tumorigenesis?

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Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation.

T Ouchi, Y Tominaga, Yi-Zhou Ye … (2006)

Aurora-A/STK15/BTAK, which encodes a centrosome-associated kinase, is amplified and overexpressed in multiple types of human tumors, including breast cancer. However, the causal relationship between overexpression of Aurora-A and tumorigenesis has not been fully established due to contradictory data obtained from different experimental systems. To investigate this, we generated a mouse strain that carries an MMTV-Aurora-A transgene. We showed that all the MMTV-Aurora-A mice displayed enhanced branch morphogenesis in the mammary gland and about 40% developed mammary tumors at 20 months of age. The tumor incidence was significantly increased in a p53(+/-) mutation background with about 70% MMTV-Aurora-A;p53(+/-) animals developed tumors at 18 months of age. Of note, overexpression of Aurora-A led to genetic instability, characterized by centrosome amplification, chromosome tetraploidization and premature sister chromatid segregation, at stages prior to tumor formation. Most notably, the severe chromosomal abnormality did not cause cell death owing to the activation of AKT pathway, including elevated levels of phosphorylated AKT and mammalian target of rapamycin, and nuclear accumulation of cyclin D1, which enabled continuous proliferation of the tetraploid cells. These data establish Aurora-A as an oncogene that causes malignant transformation through inducing genetic instability and activating oncogenic pathways such as AKT and its downstream signaling.

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Author and article information

Contributors

Hiromu Suzuki: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, USA )

ISSN (Electronic): 1932-6203

Publication date Collection: 2013

Publication date (Electronic): 13 December 2013

Volume: 8

Issue: 12

Electronic Location Identifier: e82790

Affiliations

[1 ]Department of Cardiothoracic Surgery, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China

[2 ]Department of Microbiology and Immunology, Medical School of Southeast University, Nanjing, China

[3 ]Department of Respiratory Disease, Affiliated People’s Hospital of Jiangsu University, Zhenjiang, China

Sapporo Medical University, Japan

Author notes

* E-mail: yin912@ 123456126.com (JY); haiyong_gu@ 123456hotmail.com (HG)

Competing Interests: The authors have declared that no competing interests exist.

Conceived and designed the experiments: HG JY. Performed the experiments: WT HQ HD. Analyzed the data: WT HQ HD BS LW HG JY. Contributed reagents/materials/analysis tools: HG JY. Wrote the manuscript: WT HQ HG JY.

Article

Publisher ID: PONE-D-13-31567

DOI: 10.1371/journal.pone.0082790

PMC ID: 3862673

PubMed ID: 24349361

SO-VID: 511eb8ed-618e-497d-b78c-84ec4b47f52e

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 31 July 2013

Date accepted : 28 October 2013

Funding

This study was supported by Jiangsu University Clinical medicine science and technology development fund (JLY20120004). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Association between the STK15 F31I Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 43,626 Subjects

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Most cited references 38

Genetic instabilities in human cancers.

Aurora-A - a guardian of poles.

Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation.

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