Association between nm23 gene polymorphisms and the risk of endometriosis

Huang,Xi; Zhao,Wei; Li,Yan; Kang,Shan

doi:10.3892/br.2015.511

Association between nm23 gene polymorphisms and the risk of endometriosis

Authors:
- Xi Huang
- Wei Zhao
- Yan Li
- Shan Kang
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Affiliations: Department of Molecular Biology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China, Department of Obstetrics and Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, P.R. China
Published online on: August 27, 2015 https://doi.org/10.3892/br.2015.511
Pages: 874-878

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Abstract

The first tumor metastasis-suppressor gene, nm23, may have an important role in the pathogenesis of endometriosis (EM). The present study aimed to evaluate whether nm23 gene polymorphisms are correlated with the risk of the development of EM in North Chinese women, as a preliminary study. The case‑control study was conducted with 379 EM patients and 384 unrelated healthy controls. Genotyping of two polymorphisms within the nm23 gene promoter region (rs16949649 T/C and rs2302254 C/T) were performed using polymerase chain reaction‑restriction fragment length polymorphism. The data showed that the rs16949649 and rs2302254 polymorphisms within the nm23 gene were not associated with the risk of developing EM. There were no statistical differences in the distribution of nm23 genotypes between patients with EM and the control group (P=0.490 and P=0.440, respectively). For the rs16949649 T/C, compared with the C/T + T/T genotype, the C/C genotype did not increase the risk of EM [odds ratio (OR)=0.81; 95% confidence interval (CI), 0.57‑1.17]. For the rs2302254 C/T, compared with the C/T + C/C genotype, the T/T genotype did not increase the risk of EM (OR=1.46; 95% CI, 0.81‑2.64). In conclusion, the findings in the present pilot study suggest that nm23 polymorphisms do not contribute to EM susceptibility. However, more studies in larger populations are required to confirm these results.

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1	Ballard K, Lowton K and Wright J: What's the delay? A qualitative study of women's experiences of reaching a diagnosis of endometriosis. Fertil Steril. 86:1296–1301. 2006. View Article : Google Scholar : PubMed/NCBI
2	Greene R, Stratton P, Cleary SD, Ballweg ML and Sinaii N: Diagnostic experience among 4,334 women reporting surgically diagnosed endometriosis. Fertil Steril. 91:32–39. 2009. View Article : Google Scholar : PubMed/NCBI
3	Goldman MB and Cramer DW: The epidemiology of endometriosis. Prog Clin Biol Res. 323:15–31. 1990.PubMed/NCBI
4	Treloar SA, Do KA, O'Connor VM, O'Connor DT, Yeo MA and Martin NG: Predictors of hysterectomy: An Australian study. Am J Obstet Gynecol. 180:945–954. 1999a. View Article : Google Scholar
5	Simpson JL, Bischoff FZ, Kamat A, Buster JE and Carson SA: Genetics of endometriosis. Obstet Gynecol Clin North Am. 30:21–40. 2003. View Article : Google Scholar : PubMed/NCBI
6	Zondervan KT, Cardon LR and Kennedy SH: The genetic basis of endometriosis. Curr Opin Obstet Gynecol. 13:309–314. 2001. View Article : Google Scholar : PubMed/NCBI
7	Schneider J, Jimenez E, Rodriguez F and del Tanago JG: c-myc, c-erb-B2, nm23 and p53 expression in human endometriosis. Oncol Rep. 5:49–52. 1998.PubMed/NCBI
8	Niu HY and Wang DB: Expression and significance of KISS-1 and MMP-9 gene in endometriosis model of nude mice. J Chin Med Univ. 33:487–489. 2004.
9	Li TC and Kong LN: Expression of nm23-H1 gene in endometriosis. Chin J Pathophysiology. 23:116–119. 2007.
10	Kang S, Zhao XW, Wang N, Chen SC, Zhou RM and Li Y: Association of polymorphisms of the MMP-2 and TIMP-2 genes with the risk of endometriosis in North Chinese women. Fertil Steril. 90:2023–2029. 2008. View Article : Google Scholar : PubMed/NCBI
11	Steeg PS, Bevilacqua G, Pozzatti R, Liotta LA and Sobel ME: Altered expression of NM23, a gene associated with low tumor metastatic potential, during adenovirus 2 Ela inhibition of experimental metastasis. Cancer Res. 48:6550–6554. 1988.PubMed/NCBI
12	Steeg PS: Metastasis-suppressors alter the signal transduction of cancer cells. Nat Rev Cancer. 3:55–63. 2003. View Article : Google Scholar : PubMed/NCBI
13	Lacombe ML, Milon L, Munier A, Mehus JG and Lambeth DO: The human Nm23/nucleoside diphosphate kinases. J Bioenerg Biomembr. 32:247–258. 2000. View Article : Google Scholar : PubMed/NCBI
14	Ouatas T, Salerno M, Palmieri D and Steeg PS: Basic and translational advances in cancer metastasis: Nm23. J Bioenerg Biomembr. 35:73–79. 2003. View Article : Google Scholar : PubMed/NCBI
15	Crawford RM, Treharne KJ, Best OG, Muimo R, Riemen CE and Mehta A: A novel physical and functional association between nucleoside diphosphate kinase A and AMP-activated protein kinase alpha1 in liver and lung. Biochem J. 392:201–209. 2005. View Article : Google Scholar : PubMed/NCBI
16	Steeg PS: Tumor metastasis: Mechanistic insights and clinical challenges. Nat Med. 12:895–904. 2006. View Article : Google Scholar : PubMed/NCBI
17	Mandai M, Konishi I, Koshiyama M, Mori T, Arao S, Tashiro H, Okamura H, Nomura H, Hiai H and Fukumoto M: Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: Correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. Cancer Res. 54:1825–1830. 1994.PubMed/NCBI
18	Li MQ, Shao J, Meng YH, Mei J, Wang Y, Li H, Zhang L, Chang KK, Wang XQ, Zhu XY, et al: NME1 suppression promotes growth, adhesion and implantation of endometrial stromal cells via Akt and MAPK/Erk1/2 signal pathways in the endometriotic milieu. Hum Reprod. 28:2822–2831. 2013. View Article : Google Scholar : PubMed/NCBI
19	Qu S, Long J, Cai Q, Shu XO, Cai H, Gao YT and Zheng W: Genetic polymorphisms of metastasis-suppressor gene NME1 and breast cancer survival. Clin Cancer Res. 14:4787–4793. 2008. View Article : Google Scholar : PubMed/NCBI
20	Miller SA, Dykes DD and Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 16:12151988. View Article : Google Scholar : PubMed/NCBI
21	Spuijbroek MD, Dunselman GA, Menheere PP and Evers JL: Early endometriosis invades the extracellular matrix. Fertil Steril. 58:929–933. 1992.PubMed/NCBI
22	Zeitvogel A, Baumann R and Starzinski-Powitz A: Identification of an invasive, N-cadherin-expressing epithelial cell type in endometriosis using a new cell culture model. Am J Pathol. 159:1839–1852. 2001. View Article : Google Scholar : PubMed/NCBI
23	Chang KK, Liu LB, Jin LP, Meng YH, Shao J, Wang Y, Mei J, Li MQ and Li DJ: NME1 suppression of endometrial stromal cells promotes angiogenesis in the endometriotic milieu via stimulating the secretion of IL-8 and VEGF. Int J Clin Exp Pathol. 6:2030–2038. 2013.PubMed/NCBI
24	Ouatas T, Clare SE, Hartsough MT, De La Rosa A and Steeg PS: MMTV-associated transcription factor binding sites increase nm23-H1 metastasis-suppressor gene expression in human breast carcinoma cell lines. Clin Exp Metastasis. 19:35–42. 2002. View Article : Google Scholar : PubMed/NCBI
25	Wang PH, Yi YC, Tsai HT, Tee YT, Ko JL, Han CP, Liu YF, Lin LY and Yang SF: Significant association of genetic polymorphism of human nonmetastatic clone 23 type 1 gene with an increased risk of endometrial cancer. Gynecol Oncol. 119:70–75. 2010. View Article : Google Scholar : PubMed/NCBI
26	Feng CY, Wang PH, Tsai HT, Tee YT, Ko JL, Chen SC, Lin CY, Han CP, Yang JS, Liu YF, et al: Polymorphisms of human nonmetastatic clone 23 type 1 gene and neoplastic lesions of uterine cervix. Reprod Sci. 17:886–893. 2010. View Article : Google Scholar : PubMed/NCBI
27	Ferrara N and Davis-Smyth T: The biology of vascular endothelial growth factor. Endocr Rev. 18:4–25. 1997. View Article : Google Scholar : PubMed/NCBI
28	Ferrara N, Gerber HP and LeCouter J: The biology of VEGF and its receptors. Nat Med. 9:669–676. 2003. View Article : Google Scholar : PubMed/NCBI
29	Fang F, Gong L, Wang X and Zhang L: The association between vascular endothelial growth factor (VEGF) +405G>C genetic polymorphism and endometriosis. Exp Biol Med (Maywood). Jan 7–2015.(Epub ahead of print). View Article : Google Scholar
30	Kang S, Zhao J, Liu Q, Zhou R, Wang N and Li Y: Vascular endothelial growth factor gene polymorphisms are associated with the risk of developing adenomyosis. Environ Mol Mutagen. 50:361–366. 2009. View Article : Google Scholar : PubMed/NCBI
31	Liu Q, Li Y, Zhao J, Sun DL, Duan YN, Wang N, Zhou RM and Kang S: Association of polymorphisms −1154G/A and −2578C/A in the vascular endothelial growth factor gene with decreased risk of endometriosis in Chinese women. Hum Reprod. 24:2660–2666. 2009. View Article : Google Scholar : PubMed/NCBI