Journal of Korean Medical Science

Korean Acad Medical Sciences (대한의학회)
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Intron 4 VNTR (4a/b) Polymorphism of the Endothelial Nitric Oxide Synthase Gene Is Associated with Breast Cancer in Mexican Women

  • Ramirez-Patino, Ramiro (Molecular Genetics Laboratory, Molecular Medicine Division, Western Biomedical Research Center (CIBO), Western National Medical Center (CMNO), Mexican Social Security Institute (IMSS)) ;
  • Figuera, Luis Eduardo (Genetics Division, CIBO, CMNO, IMSS) ;
  • Puebla-Perez, Ana Maria (Immunopharmacology Laboratory, Exact Sciences and Engineer University Center (CUCEI)) ;
  • Delgado-Saucedo, Jorge Ivan (Immunopharmacology Laboratory, Exact Sciences and Engineer University Center (CUCEI)) ;
  • Legazpi-Macias, Maria Magdalena (UMAE-CMNO Transplant Unit, Department of Integral Clinical Dentistry) ;
  • Mariaud-Schmidt, Rocio Patricia (Research Institute of Dentistry, Department of Integral Clinical Dentistry) ;
  • Ramos-Silva, Adriana (Molecular Genetics Laboratory, Molecular Medicine Division, Western Biomedical Research Center (CIBO), Western National Medical Center (CMNO), Mexican Social Security Institute (IMSS)) ;
  • Gutierrez-Hurtado, Itzae Adonai (Molecular Genetics Laboratory, Molecular Medicine Division, Western Biomedical Research Center (CIBO), Western National Medical Center (CMNO), Mexican Social Security Institute (IMSS)) ;
  • Gomez Flores-Ramos, Liliana (Molecular Genetics Laboratory, Molecular Medicine Division, Western Biomedical Research Center (CIBO), Western National Medical Center (CMNO), Mexican Social Security Institute (IMSS)) ;
  • Zuniga-Gonzalez, Guillermo Moises (Mutagenesis Laboratory, Molecular Medicine Division, CIBO, CMNO, IMSS) ;
  • Gallegos-Arreola, Martha Patricia (Molecular Genetics Laboratory, Molecular Medicine Division, Western Biomedical Research Center (CIBO), Western National Medical Center (CMNO), Mexican Social Security Institute (IMSS))
  • Received : 2013.03.29
  • Accepted : 2013.09.17
  • Published : 2013.11.01
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Abstract

The endothelial nitric oxide synthase (eNOS) gene plays an important role in several biological functions. Polymorphisms of the eNOS gene have been associated with cancer. It has been suggested that the VNTR 4 a/b polymorphism may affect the expression of eNOS and contributes to tumor promotion in the mammary gland. We examined the role of the eNOS4 a/b polymorphism by comparing the genotypes of 281 healthy Mexican women with the genotypes of 429 Mexican women with breast cancer (BC). The observed genotype frequencies for control and BC patients were 0.6% and 0.7% for a/a (polymorphic); 87% and 77% for a/a (wild type); and 12% and 22% for a/b respectively. We found that the odds ratio (OR) was 1.9, with a 95% confidence interval (95%CI) of 1.29-2.95, P = 0.001 for genotypes a/a-a/b, b/c. The association was also evident when comparing the distribution of the a/a-a/b genotypes in patients with high levels of glutamate-oxaloacetate transaminase (SGOT) (OR, 1.93; 95% CI, 1.14-3.28; P = 0.015); undergoing menopause with high levels of SGOT (OR, 2.0; 95% CI, 1.1-3.84); and with high levels of glutamic-pyruvic transaminase (SGPT) (OR, 3.5; 95% CI, 1.56-8.22). The genotypes a/a-a/b are associated with BC susceptibility in the analyzed samples from the Mexican population.

Keywords

References

  1. Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin 2012; 62: 220-41. https://doi.org/10.3322/caac.21149
  2. Miller JW, King JB, Joseph DA, Richardson LC; Centers for Disease Control and Prevention (CDC). Breast cancer screening among adult women: Behavioral Risk Factor Surveillance System, United States, 2010. MMWR Morb Mortal Wkly Rep 2012; 61: 46-50.
  3. Chávarri-Guerra Y, Villarreal-Garza C, Liedke PE, Knaul F, Mohar A, Finkelstein DM, Goss PE. Breast cancer in Mexico: a growing challenge to health and the health system. Lancet Oncol 2012; 13: e335-43. https://doi.org/10.1016/S1470-2045(12)70246-2
  4. Knaul FM, Nigenda G, Lozano R, Arreola-Ornelas H, Langer A, Frenk J. Breast cancer in Mexico: an urgent priority. Salud Publica Mex 2009; 51: s335-44. https://doi.org/10.1590/S0036-36342009000800026
  5. Ma Q, Lu AY. Pharmacogenetics, pharmacogenomics, and individualized medicine. Pharmacol Rev 2011; 63: 437-59. https://doi.org/10.1124/pr.110.003533
  6. Casas JP, Cavalleri GL, Bautista LE, Smeeth L, Humphries SE, Hingorani AD. Endothelial nitric oxide synthase gene polymorphisms and cardiovascular disease: a HuGE review. Am J Epidemiol 2006; 164: 921-35. https://doi.org/10.1093/aje/kwj302
  7. Xu W, Liu LZ, Loizidou M, Ahmed M, Charles IG. The role of nitric oxide in cancer. Cell Res 2002; 12: 311-20. https://doi.org/10.1038/sj.cr.7290133
  8. Lu J, Wei Q, Bondy ML, Yu TK, Li D, Brewster A, Shete S, Sahin A, Meric- Bernstam F, Wang LE. Promoter polymorphism (-786t>C) in the endothelial nitric oxide synthase gene is associated with risk of sporadic breast cancer in non-Hispanic white women age younger than 55 years. Cancer 2006; 107: 2245-53. https://doi.org/10.1002/cncr.22269
  9. Thameem F, Puppala S, Arar NH, Stern MP, Blangero J, Duggirala R, Abboud HE. Endothelial nitric oxide synthase (eNOS) gene polymorphisms and their association with type 2 diabetes-related traits in Mexican Americans. Diab Vasc Dis Res 2008; 5: 109-13. https://doi.org/10.3132/dvdr.2008.018
  10. Serrano NC, Díaz LA, Casas JP, Hingorani AD, Moreno de Lucca D, Páez MC. Frequency of eNOS polymorphisms in the Colombian general population. BMC Genet 2010; 11: 54.
  11. Yeh CC, Santella RM, Hsieh LL, Sung FC, Tang R. An intron 4 VNTR polymorphism of the endothelial nitric oxide synthase gene is associated with early-onset colorectal cancer. Int J Cancer 2009; 124: 1565-71. https://doi.org/10.1002/ijc.24114
  12. Yanamandra K, Boggs PB, Thurmon TF, Lewis D, Bocchini JA Jr, Dhanireddy R. Novel allele of the endothelial nitric oxide synthase gene polymorphism in Caucasian asthmatics. Biochem Biophys Res Commun 2005; 335: 545-9. https://doi.org/10.1016/j.bbrc.2005.07.108
  13. Via M, González-Pérez E, Esteban E, López-Alomar A, Vacca L, Vona G, Dugoujon JM, Harich N, Moral P. Molecular variation in endothelial nitric oxide synthase gene (eNOS) in western Mediterranean populations. Coll Antropol 2003; 27: 117-24.
  14. Silva PS, Lacchini R, Gomes Vde A, Tanus-Santos JE. Pharmacogenetic implications of the eNOS polymorphisms for cardiovascular action drugs. Arq Bras Cardiol 2011; 96: e27-34. https://doi.org/10.1590/S0066-782X2011000200017
  15. Li A, Song B, Zheng H, Zhang X, He Y, Xu Y. Association between the variable number of tandem repeat polymorphisms of endothelial nitric oxide synthase and ischemic cerebrovascular diseases in Henan Han ethnicity. Life Sci J 2007; 4: 26-9.
  16. Patkar S, Charita BH, Ramesh C, Padma T. High risk of essential hypertension in males with intron 4 VNTR polymorphism of eNOS gene. Indian J Hum Genet 2009; 15: 49-53. https://doi.org/10.4103/0971-6866.55215
  17. Celik U, Yildizdaş D, Alhan E, Celik T, Attila G, Sertdemir Y, Tepe T. Genetic dilemma: eNOS gene intron 4a/b VNTR polymorphism in sepsis and its clinical features in Turkish children. Turk J Pediatr 2008; 50: 114-9.
  18. Gan YY, Chen CF. The 27-bp VNTR polymorphism in intron 4 of the human eNOS gene in healthy Singaporean Chinese, Indians, and Malays. Biochem Genet 2012; 50: 52-62. https://doi.org/10.1007/s10528-011-9458-0
  19. Rusai K, Vannay A, Szebeni B, Borgulya G, Fekete A, Vásárhelyi B, Tulassay T, Szabó AJ. Endothelial nitric oxide synthase gene T-786C and 27- bp repeat gene polymorphisms in retinopathy of prematurity. Mol Vis 2008; 14: 286-90.
  20. Deng F, Hu Q, Tang B, He F, Guo S, Chen J, Li F, Wu X, Zhang J, Zhang H, et al. Endothelial nitric oxide synthase gene intron 4, 27 bp repeat polymorphism and essential hypertension in the Kazakh Chinese population. Acta Biochim Biophys Sin (Shanghai) 2007; 39: 311-6. https://doi.org/10.1111/j.1745-7270.2007.00285.x
  21. Moreno H Jr. Genetic polymorphisms and haplotypes of eNOS in breast cancer. Breast Cancer Res Treat 2008; 109: 181-2. https://doi.org/10.1007/s10549-007-9630-8
  22. Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215. https://doi.org/10.1093/nar/16.3.1215
  23. Yoon Y, Song J, Hong SH, Kim JQ. Plasma nitric oxide concentrations and nitric oxide synthase gene polymorphisms in coronary artery disease. Clin Chem 2000; 46: 1626-30.
  24. Sanguinetti CJ, Dias Neto E, Simpson AJ. Rapid silver staining and recovery of PCR products separated on polyacrylamide gels. Biotechniques 1994; 17: 914-21.
  25. Naieni KH, Ardalan A, Mahmoodi M, Motevalian A, Yahyapoor Y, Yazdizadeh B. Risk factors of breast cancer in north of Iran: a case-control in Mazandaran Province. Asian Pac J Cancer Prev 2007; 8: 395-8.
  26. Macciò A, Madeddu C. Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications. ScientificWorldJournal 2011; 11:2020-36. https://doi.org/10.1100/2011/806787
  27. IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Combined estrogen-progestogen contraceptives and combined estrogen- progestogen menopausal therapy. IARC Monogr Eval Carcinog Risks Hum 2007; 91: 1-528.
  28. Lazcano-Ponce EC, Tovar-Guzmán V, Alonso-de Ruiz P, Romieu I, López- Carrillo L. Breast cancer: a historical account, present and future. Salud Publica Mex 1996; 38: 139-52.
  29. Anothaisintawee T, Wiratkapun C, Lerdsitthichai P, Kasamesup V, Wongwaisayawan S, Srinakarin J, Hirunpat S, Woodtichartpreecha P, Boonlikit S, Teerawattananon Y, et al. Risk factors of breast cancer: a systematic review and meta-analysis. Asia Pac J Public Health 2013; 25: 368-87. https://doi.org/10.1177/1010539513488795
  30. Yu ZG, Jia CX, Liu LY, Geng CZ, Tang JH, Zhang J, Zhang Q, Li YY, Ma ZB. The prevalence and correlates of breast cancer among women in Eastern China. PLoS One 2012; 7: e37784. https://doi.org/10.1371/journal.pone.0037784
  31. Jiang AR, Gao CM, Ding JH, Li SP, Liu YT, Cao HX, Wu JZ, Tang JH, Qian Y, Tajima K. Abortions and breast cancer risk in premenopausal and postmenopausal women in Jiangsu Province of China. Asian Pac J Cancer Prev 2012; 13: 33-5. https://doi.org/10.7314/APJCP.2012.13.1.033
  32. Cines DB, Pollak ES, Buck CA, Loscalzo J, Zimmerman GA, McEver RP, Pober JS, Wick TM, Konkle BA, Schwartz BS, et al. Endothelial cells in physiology and in the pathophysiology of vascular disorders. Blood 1998; 91: 3527-61.
  33. Tecder Ünal M, Karabulut HG, Gümüş-Akay G, Dölen Y, Elhan A, Tükün A, Ünal AE. Endothelial nitric oxide synthase gene polymorphism in gas tric cancer. Turk J Gastroenterol 2010; 21: 338-44. https://doi.org/10.4318/tjg.2010.0118
  34. Thornburg JM, Nelson KK, Clem BF, Lane AN, Arumugam S, Simmons A, Eaton JW, Telang S, Chesney J. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res 2008; 10: R84. https://doi.org/10.1186/bcr2154
  35. Amin KA, Mohamed BM, El-Wakil MA, Ibrahem SO. Impact of breast cancer and combination chemotherapy on oxidative stress, hepatic and cardiac markers. J Breast Cancer 2012; 15: 306-12. https://doi.org/10.4048/jbc.2012.15.3.306

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