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Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2007

01-12-2007 | Epidemiology

Genetic polymorphisms of NOS3 are associated with the risk of invasive breast cancer with lymph node involvement

Authors: Kyoung-Mu Lee, Ji-Yeob Choi, Jong Eun Lee, Dong-Young Noh, Sei-Hyun Ahn, Wonshik Han, Keun-Young Yoo, Richard B. Hayes, Daehee Kang

Published in: Breast Cancer Research and Treatment | Issue 3/2007

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Abstract

Endothelial nitric oxide synthase (NOS3) produces nitric oxide which is a mediator of cytotoxic effects potentially associated with breast cancer. We evaluated the role of genetic polymorphisms of NOS3 in breast cancer etiology, in a case–control study conducted in Korea. We recruited 1,385 eligible patients with histologicaly confirmed incident breast cancer cases and 968 hospital-based controls. Two potentially functional NOS3 polymorphisms in the promoter region (−786T > C) and exon 7 (894G > T, Glu298Asp) were genotyped and individual haplotypes were estimated. Odds ratios (ORs) and 95% confidential intervals (95% CIs) were calculated by unconditional logistic regression, adjusting for age, body mass index, education, family history of breast cancer in first and second degree relatives, age at first full-term pregnancy and parity. There was no overall association between the −786T > C or 894G > T genotype and breast cancer risk. However, the −786C allele was marginally associated with decreased risk for invasive breast cancer with lymph node involvement (OR = 0.76, 95% CI = 0.56–1.04). And, compared to TG-TG carriers, all other haplotype pairs were significantly associated with invasive breast cancer with lymph node involvement (OR = 0.77, 95% CI = 0.59–0.99). Our results suggest that genetic polymorphisms in NOS3 modify individual susceptibility to invasive breast cancer with lymph node involvement in Korean women.
Literature
1.
Loibl S, Buck A, Strank C, von Minckwitz G, Roller M, Sinn HP, Schini-Kerth V, Solbach C, Strebhardt K, Kaufmann M (2005) The role of early expression of inducible nitric oxide synthase in human breast cancer. Eur J Cancer 41(2):265–271PubMedCrossRef
2.
Thomsen LL, Miles DW (1998) Role of nitric oxide in tumour progression: lessons from human tumours. Cancer Metast Rev 17(1):107–118 CrossRef
3.
Lala PK, Orucevic A (1998) Role of nitric oxide in tumor progression: lessons from experimental tumors. Cancer Metast Rev 81:889–896
4.
Forstermann U, Boissel JP, Kleinert H (1998) Expressional control of the ‘constitutive’ isoforms of nitric oxide synthase (NOS I and NOS III). FASEB J 12(10):773–790 PubMed
5.
Hingorani AD (2003) Endothelial nitric oxide synthase polymorphisms and hypertension. Curr Hypertens Rep 5(1):19–25PubMedCrossRef
6.
Rao S, Austin H, Davidoff MN, Zafari AM (2005) Endothelial nitric oxide synthase intron 4 polymorphism is a marker for coronary artery disease in African–American and Caucasian men. Ethn Dis 15(2):191–197PubMed
7.
Yoshimura T, Yoshimura M, Tabata A, Shimasaki Y, Nakayama M, Miyamoto Y, Saito Y, Nakao K, Yasue H, Okamura H (2000) Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with severe preeclampsia. J Soc Gynecol Investig 7(4):238–241PubMedCrossRef
8.
Ntais C, Polycarpou A (2005) Association of the endothelial nitric oxide synthase (NOS3) Glu298Asp gene polymorphism with the risk of Alzheimer’s disease––a meta-analysis. J Neurol 252(10):1276–1278PubMedCrossRef
9.
Ghilardi G, Biondi ML, Cecchini F, DeMonti M, Guagnellini E, Scorza R (2003) Vascular invasion in human breast cancer is correlated to T786C polymorphism of NOS3 gene. Nitric Oxide 9(2):118–122PubMedCrossRef
10.
Hefler LA, Ludwig E, Lampe D, Zeillinger R, Leodolter S, Gitsch G, Koelbl H, Tempfer CB (2002) Polymorphisms of the endothelial nitric oxide synthase gene in ovarian cancer. Gynecol Oncol 86(2):134–137PubMedCrossRef
11.
Medeiros R, Morais A, Vasconcelos A, Costa S, Pinto D, Oliveira J, Lopes C (2002) Endothelial nitric oxide synthase gene polymorphisms and genetic susceptibility to prostate cancer. Eur J Cancer Prev 11(4):343–350PubMedCrossRef
12.
Hefler LA, Grimm C, Lantzsch T, Lampe D, Koelbl H, Lebrecht A, Heinze G, Tempfer C, Reinthaller A, Zeillinger R (2006) Polymorphisms of the endothelial nitric oxide synthase gene in breast cancer. Breast Cancer Res Treat 98(2):151–155PubMedCrossRef
13.
Lu J, Wei Q, Bondy ML, Yu TK, Li D, Brewster A, Shete S, Sahin A, Meric-Bernstam F, Wang LE (2006) 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 107(9):2245–2253PubMedCrossRef
14.
Royo JL, Moreno-Nogueira JA, Galan JJ, Gonzalez-Martin A, Ruiz A, Gonzalez-Mancha R, Real LM (2006) Lack of association between NOS3 Glu298Asp and breast cancer risk: a case–control study. Breast Cancer Res Treat 100(3):331–333PubMedCrossRef
15.
Choi JY, Lee KM, Noh DY, Ahn SH, Lee JE, Han W, Jang IJ, Shin SG, Yoo KY, Hayes RB, Kang D (2006) Genetic polymorphisms of eNOS, hormone receptor status, and survival of breast cancer. Breast Cancer Res Treat 100(2):213–218PubMedCrossRef
16.
Stephens M, Donnelly P (2003) A comparison of Bayesian methods for haplotype reconstruction from population genotype data. Am J Hum Genet 73:1162–1169PubMedCrossRef
17.
Page GP, Amos CI (1999) Comparison of linkage-disequilibrium methods for localization of genes influencing quantitative traits in humans. Am J Hum Genet 64(4):1194–1205PubMedCrossRef
18.
Martin JH, Begum S, Alalami O, Harrison A, Scott KW (2000) Endothelial nitric oxide synthase: correlation with histologic grade, lymph node status and estrogen receptor expression in human breast cancer. Tumour Biol 21(2):90–97PubMedCrossRef
19.
Loibl S, Strank C, von Minckwitz G, Sinn HP, Buck A, Solbach C, Strebhardt K, Kaufmann M (2005) Immunohistochemical evaluation of endothelial nitric oxide synthase expression in primary breast cancer. Breast 14:230–235PubMedCrossRef
20.
Tanus-Santos JE, Desai M, Deak LR, Pezzullo JC, Abernethy DR, Flockhart DA, Freedman JE (2002) Effects of endothelial nitric oxide synthase gene polymorphisms on platelet function, nitric oxide release, and interactions with estradiol. Pharmacogenetics 12(5): 407–413PubMedCrossRef
21.
Thomsen LL, Miles DW, Happerfield L, Bobrow LG, Knowles RG, Moncada S (1995) Nitric oxide synthase activity in human breast cancer. Br J Cancer 72(1):41–44PubMed
22.
Jadeski LC, Hum KO, Chakraborty C, Lala PK (2000) Nitric oxide promotes murine mammary tumour growth and metastasis by stimulating tumour cell migration, invasiveness and angiogenesis. Int J Cancer 86(1):30–39PubMedCrossRef
23.
Tse GM, Wong FC, Tsang AK, Lee CS, Lui PC, Lo AW, Law BK, Scolyer RA, Karim RZ, Putti TC (2005) Stromal nitric oxide synthase (NOS) expression correlates with the grade of mammary phyllodes tumour. J Clin Pathol 58(6):600–604PubMedCrossRef
24.
Nakamura Y, Yasuoka H, Tsujimoto M, Yoshidome K, Nakahara M, Nakao K, Nakamura M, Kakudo K (2006) Nitric oxide in breast cancer: induction of vascular endothelial growth factor-C and correlation with metastasis and poor prognosis. Clin Cancer Res 12(4):1201–1207PubMedCrossRef
25.
Nakayama M, Yasue H, Yoshimura M, Shimasaki Y, Kugiyama K, Ogawa H, Motoyama T, Saito Y, Ogawa Y, Miyamoto Y, Nakao K (1999) T-786–>C mutation in the 5′-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 99(22):2864–2870PubMed
26.
Wang J, Dudley D, Wang XL (2002) Haplotype-specific effects on endothelial NO synthase promoter efficiency: modifiable by cigarette smoking. Arterioscler Thromb Vasc Biol 22(5):e1–e4PubMedCrossRef
27.
Ahsan A, Norboo T, Baig MA, Qadar Pasha MA (2005) Simultaneous selection of the wild-type genotypes of the G894T and 4B/ 4A polymorphisms of NOS3 associate with high-altitude adaptation. Ann Hum Genet 69(Pt 3):260–267 PubMedCrossRef
28.
Tesauro M, Thompson WC, Rogliani P, Qi L, Chaudhary PP, Moss J (2000) Intracellular processing of endothelial nitric oxide synthase isoforms associated with differences in severity of cardiopulmonary diseases: cleavage of proteins with aspartate vs. glutamate at position 298. Proc Natl Acad Sci USA 97(6):2832–2835PubMedCrossRef
29.
Fairchild TA, Fulton D, Fontana JT, Gratton JP, McCabe TJ, Sessa WC (2001) Acidic hydrolysis as a mechanism for the cleavage of the Glu(298)→Asp variant of human endothelial nitric-oxide synthase. J Biol Chem 276(28):26674–26679PubMedCrossRef
30.
Mortensen K, Holck S, Christensen IJ, Skouv J, Hougaard DM, Blom J, Larsson LI (1999) Endothelial cell nitric oxide synthase in peritumoral microvessels is a favorable prognostic indicator in premenopausal breast cancer patients. Clin Cancer Res 5(5):1093–1097PubMed
31.
Jadeski LC, Chakraborty C, Lala PK (2003) Nitric oxide-mediated promotion of mammary tumour cell migration requires sequential activation of nitric oxide synthase, guanylate cyclase and mitogen-activated protein kinase. Int J Cancer 106(4):496–504PubMedCrossRef
Metadata
Title
Genetic polymorphisms of NOS3 are associated with the risk of invasive breast cancer with lymph node involvement
Authors
Kyoung-Mu Lee
Ji-Yeob Choi
Jong Eun Lee
Dong-Young Noh
Sei-Hyun Ahn
Wonshik Han
Keun-Young Yoo
Richard B. Hayes
Daehee Kang
Publication date
01-12-2007
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2007
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-007-9506-y

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