DOI QR코드

DOI QR Code

Nitric Oxide Synthase 3 Gene Variants and Colorectal Cancer: a Meta-Analysis

  • Chen, Yang (Center for Genomic and Personalized Medicine, Guangxi Medical University) ;
  • Li, Jie (Center for Genomic and Personalized Medicine, Guangxi Medical University) ;
  • Guo, Yun (Department of Anorectal Surgery, The First Affiliated Hospital of Guangxi Medical University) ;
  • Guo, Xiao-Yun (Department of Gastroenterology, The First Affiliated Hospital of Guangxi Medical University)
  • Published : 2014.04.30

Abstract

Background: Colorectal cancer (CRC) is the worldwide disease which causes enormous losses every year. Recent studies suggested that environmental and gene factors might be the etiologies in increasing the risk of morbidity. Nitric oxide synthase 3 (NOS3) gene polymorphisms are said to be associated with CRC risk but the conclusion is still controversial. Materials and Methods: Pubmed and HuGENet databases up to December 2013 were used in this meta-analysis. Three different certain genotypic models were applied, namely dominant (AA+AC versus CC), recessive (AA versus AC+CC), per-allele analysis (A vs C). In addition, information on tumor sites and pathologic stages was collected. The strength of associations was assessed through combining odds ratio (OR) and 95% confidence interval (CI). Results: Finally, five and three studies about the rs1799983 and rs2070744 were covered in the analysis with 2,745 cases and 2,478 controls. Three models were applied, but no significant association was found for NOS3 G894T/rs1799983 (dominant: OR=0.999, 95%CI=0.797-1.253, $I^2$=63.8%; recessive: OR=0.924, 95%CI=0.589-1.450, $I^2$=59.3%; allele analysis: OR=0.979, 95%CI=0.788-1.216, $I^2$=74.9%) and T-786C/rs2070744 (dominant: OR=1.138, 95%CI=0.846-1.530, $I^2$=67.9%; recessive: OR=0.956, 95%CI=0.708-1.291, $I^2$=0.0%; allele analysis: OR=1.110, 95%CI=0.865-1.425, $I^2$=69.4%). The same results were also obtained for tumor sites and pathologic stage subgroups. After further analyzing the NOS3 gene, rs1799983 as the tag- and functional SNP was presented. Conclusions: On the basis of this meta-analysis and the characteristics of the NOS3 gene, we suggested rs1799983 might be a key locus associated with CRC risk. Further prospective studies were needed to make more comprehensive explanation of the associations.

Acknowledgement

Supported by : National Natural Science Foundation of China

References

  1. Chaleshi V, Haghighi MM, Savabkar S, et al (2013). Correlation between the EGF gene intronic polymorphism, rs2298979, and colorectal cancer. Oncol Lett, 6, 1079-83.
  2. Brankovic A, Brajuskovic G, Nikolic Z, et al (2013). Endothelial nitric oxide synthase gene polymorphisms and prostate cancer risk in Serbian population. Int J Exp Pathol, 94, 355-61. https://doi.org/10.1111/iep.12045
  3. Center MM, Jemal A, Smith RA, Ward E (2009). Worldwide variations in colorectal cancer. CA Cancer J Clin, 59, 366-78. https://doi.org/10.3322/caac.20038
  4. Conde MC, Ramirez-Lorca R, Lopez-Jamar JM, et al (2006). Genetic analysis of caveolin-1 and eNOS genes in colorectal cancer. Oncol Rep, 16, 353-9.
  5. Cunningham D, Atkin W, Lenz HJ, et al (2010). Colorectal cancer. Lancet, 375, 1030-47. https://doi.org/10.1016/S0140-6736(10)60353-4
  6. Dan S, Bai L, Li-Jie W, Ting Z, Zhi-Yuan M (2013). Pharmacogenetic angiogenesis profiling for first-line chemotherapy in patients with advanced gastric cancer. Cancer Invest, 31, 390-6. https://doi.org/10.3109/07357907.2013.795580
  7. Egger M, Davey Smith G, Schneider M, Minder C (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34. https://doi.org/10.1136/bmj.315.7109.629
  8. Fatini C, Sofi F, Sticchi E, et al (2004). Influence of endothelial nitric oxide synthase gene polymorphisms (G894T, 4a4b, T-786C) and hyperhomocysteinemia on the predisposition to acute coronary syndromes. Am Heart J, 147, 516-21. https://doi.org/10.1016/j.ahj.2003.10.032
  9. Fraga LR, Paludo FJ, Bos AJ, et al (2013). More severe clinical course of cardiovascular dysfunction in intensive care unit patients with the 894TT eNOS genotype. Genet Mol Res, 12, 562-8. https://doi.org/10.4238/2013.February.27.5
  10. Funke S, Hoffmeister M, Brenner H, Chang-Claude J (2009a). Effect modification by smoking on the association between genetic polymorphisms in oxidative stress genes and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev. 18, 2336-8. https://doi.org/10.1158/1055-9965.EPI-09-0507
  11. Aguilar-Melero P, Ferrin G, Muntane J (2012). Effects of nitric oxide synthase-3 overexpression on post-translational modifications and cell survival in HepG2 cells. J Proteomics, 75, 740-55. https://doi.org/10.1016/j.jprot.2011.09.010
  12. Ames BN (1983). Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science, 221, 1256-64 https://doi.org/10.1126/science.6351251
  13. Arikan S, Cacina C, Guler E, et al (2012). The effects of NOS3 Glu298Asp variant on colorectal cancer risk and progression in Turkish population. Mol Biol Rep, 39, 3245-9. https://doi.org/10.1007/s11033-011-1092-8
  14. Moochhala S, Chhatwal VJ, Chan ST, et al (1996). Nitric oxide synthase activity and expression in human colorectal cancer. Carcinogenesis, 17, 1171-4. https://doi.org/10.1093/carcin/17.5.1171
  15. Yagihashi N, Kasajima H, Sugai S, et al (2000). Increased in situ expression of nitric oxide synthase in human colorectal cancer. Virchows Arch, 436, 109-14. https://doi.org/10.1007/PL00008208
  16. Yeh CC, Santella RM, Hsieh LL, Sung FC, Tang R (2009). An intron 4 VNTR polymorphism of the endothelial nitric oxide synthase gene is associated with early-onset colorectal cancer. Int J Cancer, 124, 1565-71. https://doi.org/10.1002/ijc.24114
  17. Zhao P, Dai M, Chen W, Li N (2010). Cancer trends in China. Jpn J Clin Oncol, 40, 281-5. https://doi.org/10.1093/jjco/hyp187
  18. Lau J, Ioannidis JP, Schmid CH (1997). Quantitative synthesis in systematic reviews. Ann Intern Med, 127, 820-6. https://doi.org/10.7326/0003-4819-127-9-199711010-00008
  19. Luo L, Li DH, Wei SG, et al (2013). Polymorphisms in the endothelial nitric oxide synthase gene associated with recurrent miscarriage. Genet Mol Res, 12, 3879-86. https://doi.org/10.4238/2013.September.23.6
  20. Oh NJ, Ryu KY, Jung CN, Yi SY, Kim SR (2013). Expression of endothelial nitric oxide synthase in the uterus of patients with leiomyoma or adenomyosis. J Obstet Gynaecol Res, 39, 536-42. https://doi.org/10.1111/j.1447-0756.2012.01980.x
  21. Pfeifer GP, Denissenko MF, Olivier M, et al (2002). Tobacco smoke carcinogens, DNA damage and p53 mutations in smoking-associated cancers. Oncogene, 21, 7435-51 https://doi.org/10.1038/sj.onc.1205803
  22. Razavi HM, Hamilton JA, Feng Q (2005). Modulation of apoptosis by nitric oxide: implications in myocardial ischemia and heart failure. Pharmacol Ther, 106, 147-62. https://doi.org/10.1016/j.pharmthera.2004.11.006
  23. Ryk C, Wiklund NP, Nyberg T, de Verdier PJ (2011). Polymorphisms in nitric-oxide synthase 3 may influence the risk of urinary-bladder cancer. Nitric Oxide, 25, 338-43. https://doi.org/10.1016/j.niox.2011.06.003
  24. Terrazzino S, La Mattina P, Masini L, et al (2012). Common variants of eNOS and XRCC1 genes may predict acute skin toxicity in breast cancer patients receiving radiotherapy after breast conserving surgery. Radiother Oncol, 103, 199-205. https://doi.org/10.1016/j.radonc.2011.12.002
  25. Verim L, Toptas B, Ozkan NE, et al (2013). Possible relation between the NOS3 gene GLU298ASP polymorphism and bladder cancer in Turkey. Asian Pac J Cancer Prev, 14, 665-8. https://doi.org/10.7314/APJCP.2013.14.2.665
  26. Yao L, Fang F, Zhong Y, Yu L (2010). The association between two polymorphisms of eNOS and breast cancer risk: a metaanalysis. Breast Cancer Res Treat, 124, 223-7. https://doi.org/10.1007/s10549-010-0800-8
  27. Ikeda S, Sasazuki S, Natsukawa S, et al (2008). Screening of 214 single nucleotide polymorphisms in 44 candidate cancer susceptibility genes: a case-control study on gastric and colorectal cancers in the Japanese population. Am J Gastroenterol, 103, 1476-87. https://doi.org/10.1111/j.1572-0241.2008.01810.x
  28. Funke S, Risch A, Nieters A, et al (2009b). Genetic polymorphisms in genes related to oxidative stress (GSTP1, GSTM1, GSTT1, CAT, MnSOD, MPO, eNOS) and survival of rectal cancer patients after radiotherapy. J Cancer Epidemiol, 2009, 302047.
  29. Hildebrandt MA, Komaki R, Liao Z, et al (2010). Genetic variants in inflammation-related genes are associated with radiation-induced toxicity following treatment for non-small cell lung cancer. PLoS One, 5, 12402. https://doi.org/10.1371/journal.pone.0012402
  30. Ho-Pun-Cheung A, Assenat E, Bascoul-Mollevi C, et al (2011). A large-scale candidate gene approach identifies SNPs in SOD2 and IL13 as predictive markers of response to preoperative chemoradiation in rectal cancer. Pharmacogenomics J, 11, 437-43. https://doi.org/10.1038/tpj.2010.62
  31. Jang MJ, Jeon YJ, Kim JW, et al (2013). Association of eNOS polymorphisms (-786T>C, 4a4b, 894G>T) with colorectal cancer susceptibility in the Korean population. Gene, 512, 275-81. https://doi.org/10.1016/j.gene.2012.10.032
  32. Jemal A, Siegel R, Xu J, Ward E (2010). Cancer statistics, 2010. CA Cancer J Clin, 60, 277-300. https://doi.org/10.3322/caac.20073
  33. Kassab A, Msolly A, Lakhdar R, Gharbi O, Miled A (2014). Polymorphisms of glutathione-S-transferases M1, T1, P1 and susceptibility to colorectal cancer in a sample of the Tunisian population. Med Oncol, 31, 760. https://doi.org/10.1007/s12032-013-0760-z
  34. Kelly RA, Balligand JL, Smith TW (1996). Nitric oxide and cardiac function. Circulation Research, 79, 363-80. https://doi.org/10.1161/01.RES.79.3.363
  35. Kim YJ, Lee SJ, Kim JG, et al (2011). No association of the eNOS gene polymorphisms with survival in patients with colorectal cancer. Med Oncol, 28, 1075-9. https://doi.org/10.1007/s12032-010-9647-4

Cited by

  1. Seniors Have a Better Learning Curve for Laparoscopic Colorectal Cancer Resection vol.15, pp.13, 2014, https://doi.org/10.7314/APJCP.2014.15.13.5395
  2. G894T and 4a/b Polymorphisms of NOS3 Gene are Not Associated with Cancer Risk: a Meta-analysis vol.16, pp.7, 2015, https://doi.org/10.7314/APJCP.2015.16.7.2929