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Int. J. Mol. Sci. 2014, 15(12), 22902-22917; doi:10.3390/ijms151222902

Associations of NR5A2 Gene Polymorphisms with the Clinicopathological Characteristics and Survival of Gastric Cancer

1
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China
2
Department of Oncology, Nantong Tumor Hospital, Nantong 226300, China
3
Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, Nanjing 211166, China
4
Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China
5
Department of Surgery, Yixing People's Hospital, Yixing 214200, China
6
Department of General Surgery, Yixing Tumor Hospital, Yixing 214200, China
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 22 September 2014 / Revised: 15 October 2014 / Accepted: 16 November 2014 / Published: 10 December 2014
(This article belongs to the Collection Human Single Nucleotide Polymorphisms and Disease Diagnostics)
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Abstract

The orphan nuclear receptor (NR5A2), which belongs to the NR5A subfamily of nuclear receptors, is expressed in developing and adult tissues of endodermal origin, and can contribute to the development of several cancers through regulating cell proliferation. NR5A2 (rs3790843 and rs3790844) single nucleotide polymorphisms (SNPs) genotyping were examined in DNA samples, extracted from paraffin-embedded cancer tissue. Clinicopathologic and follow-up data were collected from 944 patients with gastric cancer (GC). Associations of the 2 SNPs with the progression and prognosis in gastric cancer patients were analyzed using the SPSS version 18.0. We found that NR5A2 rs3790843 polymorphism was significantly associated with the risk of GC which had regional lymph node metastasis (p = 0.044) or distant metastasis (p = 0.020). Our results also indicated that rs3790844 polymorphism was associated with the increased overall survival (OS) of GC patients in the dominant model (GG vs. GA/AA, HR (hazard ratio) = 0.823, 95% CI (confidence interval) = 0.679–0.997), suggesting a potential protective role of the variant A allele. Additionally, in the stratified analysis, both NR5A2 rs3790843 and rs3790844 polymorphism were associated with significantly lower risk of death in the groups of female, tumor size >5 cm in a dominant model. Our results represent the first demonstration that the NR5A2 rs3790844 polymorphism is associated with increased OS of GC patients in the dominant model, and similar results were found among the female group and tumor size >5 cm group for NR5A2 rs3790843 polymorphism. Further validation in other larger studies with different ethnic populations and functional evaluations are needed. View Full-Text
Keywords: NR5A2; rs3790843; rs3790844; single nucleotide polymorphism; gastric cancer NR5A2; rs3790843; rs3790844; single nucleotide polymorphism; gastric cancer
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Zhang, X.; Gu, D.; Du, M.; Wang, M.; Cao, C.; Shen, L.; Kuang, M.; Tan, Y.; Huo, X.; Gong, W.; Xu, Z.; Chen, J.; Zhang, Z.; Tang, C. Associations of NR5A2 Gene Polymorphisms with the Clinicopathological Characteristics and Survival of Gastric Cancer. Int. J. Mol. Sci. 2014, 15, 22902-22917.

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