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Published in: Pathology & Oncology Research 2/2016

01-04-2016 | Original Article

ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer

Authors: Batoul Kaabi, Ghania Belaaloui, Wassila Benbrahim, Kamel Hamizi, Mourad Sadelaoud, Wided Toumi, Hocine Bounecer

Published in: Pathology & Oncology Research | Issue 2/2016

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Abstract

Breast cancer (BC) prognosis and risk were associated to obesity, metabolic syndrome and type 2 diabetes mellitus. Two Single Nucleotide Polymorphisms (SNPs) of the adrenergic receptor-2a gene (ADRA2A): rs1800544 and rs553668, have been associated to these metabolic disorders. We investigated these SNPs in BC risk and prognosis. A total of 102 BC patients and 102 healthy controls were included. The rs1800544 and rs553668 were determined by real-time PCR. Genotypes and haplotypes frequencies between patients and controls, and for different clinico-pathologic parameters were compared. We found a significant association of rs1800544 GG genotype with young age at diagnosis, premenopausal status, higher tumor size, metastasis in lymph nodes, advanced TNM stages and higher Nottingham Prognosis Indicator (NPI) (p < 0.05). There was no association between rs1800544 and SBR stages, Her2, ER and PR statuses and the molecular classification. The rs553668 AA genotype was associated to young age at diagnosis and premenopausal status (p < 0.05). The haplotype GA was associated to the early age of diagnosis (p = 0.03), and the haplotype GG to higher tumor size, lymph node involvement, advanced TNM stages and Her2 positive status (p < 0.05). There was no polymorphism or haplotype association with BC risk (p > 0.05). ADRA2A polymorphism is associated with indicators BC poor prognosis but not with BC susceptibility. This is the first report suggesting that ADRA2A germline gene polymorphism could represent a predictor factor for BC outcome. Further investigation of other ADRA2A polymorphisms in BC risk or prognosis are needed and may lead to a genotype-based therapy.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2013) GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide. IARC CancerBase 2012; No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer. Available from: http://globocan.iarc.fr. Accessed on 2019th Dec 2014 Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F (2013) GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide. IARC CancerBase 2012; No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer. Available from: http://​globocan.​iarc.​fr. Accessed on 2019th Dec 2014
2.
go back to reference Pusztai L (2011) Anatomy and biology: two complementary sides of breast cancer prognostication. J Clin Oncol 29(33):4347–4348CrossRefPubMed Pusztai L (2011) Anatomy and biology: two complementary sides of breast cancer prognostication. J Clin Oncol 29(33):4347–4348CrossRefPubMed
3.
go back to reference Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, et al. (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 22(8):1736–1747CrossRefPubMedPubMedCentral Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thurlimann B, et al. (2011) Strategies for subtypes–dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 22(8):1736–1747CrossRefPubMedPubMedCentral
4.
go back to reference Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, et al. (2013) Personalizing the treatment of women with early breast cancer: highlights of the St gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol 24(9):2206–2223CrossRefPubMedPubMedCentral Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, et al. (2013) Personalizing the treatment of women with early breast cancer: highlights of the St gallen international expert consensus on the primary therapy of early breast cancer 2013. Ann Oncol 24(9):2206–2223CrossRefPubMedPubMedCentral
5.
go back to reference Zhang B, Beeghly-Fadiel A, Long J, Zheng W (2011) Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol 12(5):477–488CrossRefPubMedPubMedCentral Zhang B, Beeghly-Fadiel A, Long J, Zheng W (2011) Genetic variants associated with breast-cancer risk: comprehensive research synopsis, meta-analysis, and epidemiological evidence. Lancet Oncol 12(5):477–488CrossRefPubMedPubMedCentral
6.
go back to reference Rafiq S, Khan S, Tapper W, Collins A, Upstill-Goddard R, et al. (2014) A genome wide meta-analysis study for identification of common variation associated with breast cancer prognosis. PLoS One 9(12):e101488CrossRefPubMedPubMedCentral Rafiq S, Khan S, Tapper W, Collins A, Upstill-Goddard R, et al. (2014) A genome wide meta-analysis study for identification of common variation associated with breast cancer prognosis. PLoS One 9(12):e101488CrossRefPubMedPubMedCentral
7.
go back to reference Sapkota Y (2014) Germline DNA variations in breast cancer predisposition and prognosis: a systematic review of the literature. Cytogenet Genome Res 144(2):77–91CrossRefPubMed Sapkota Y (2014) Germline DNA variations in breast cancer predisposition and prognosis: a systematic review of the literature. Cytogenet Genome Res 144(2):77–91CrossRefPubMed
8.
go back to reference Ribelles N, Santonja A, Pajares B, Llacer C, Alba E (2014) The seed and soil hypothesis revisited: current state of knowledge of inherited genes on prognosis in breast cancer. Cancer Treat Rev 40(2):293–299CrossRefPubMed Ribelles N, Santonja A, Pajares B, Llacer C, Alba E (2014) The seed and soil hypothesis revisited: current state of knowledge of inherited genes on prognosis in breast cancer. Cancer Treat Rev 40(2):293–299CrossRefPubMed
9.
go back to reference Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, et al. (1987) Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science 238(4827):650–656CrossRefPubMed Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, et al. (1987) Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science 238(4827):650–656CrossRefPubMed
10.
go back to reference Hoffman BB, Taylor P (2001) Neurotransmission: the autonomic and somatic motor nervous systems. In: Hardman JG, Limbird LE, Gilman AG (eds) Goodman & Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, New York, pp. 115–153 Hoffman BB, Taylor P (2001) Neurotransmission: the autonomic and somatic motor nervous systems. In: Hardman JG, Limbird LE, Gilman AG (eds) Goodman & Gilman’s the pharmacological basis of therapeutics. McGraw-Hill, New York, pp. 115–153
11.
go back to reference Lario S, Calls J, Cases A, Oriola J, Torras A, et al. (1997) MspI identifies a biallelic polymorphism in the promoter region of the alpha 2A-adrenergic receptor gene. Clin Genet 51(2):129–130CrossRefPubMed Lario S, Calls J, Cases A, Oriola J, Torras A, et al. (1997) MspI identifies a biallelic polymorphism in the promoter region of the alpha 2A-adrenergic receptor gene. Clin Genet 51(2):129–130CrossRefPubMed
12.
go back to reference Lima JJ, Feng H, Duckworth L, Wang J, Sylvester JE, et al. (2007) Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism 56(6):757–765CrossRefPubMedPubMedCentral Lima JJ, Feng H, Duckworth L, Wang J, Sylvester JE, et al. (2007) Association analyses of adrenergic receptor polymorphisms with obesity and metabolic alterations. Metabolism 56(6):757–765CrossRefPubMedPubMedCentral
13.
go back to reference Garenc C, Perusse L, Chagnon YC, Rankinen T, Gagnon J, et al. (2002) The alpha 2-adrenergic receptor gene and body fat content and distribution: the HERITAGE family study. Mol Med 8(2):88–94PubMedPubMedCentral Garenc C, Perusse L, Chagnon YC, Rankinen T, Gagnon J, et al. (2002) The alpha 2-adrenergic receptor gene and body fat content and distribution: the HERITAGE family study. Mol Med 8(2):88–94PubMedPubMedCentral
14.
go back to reference Kurnik D, Muszkat M, Li C, Sofowora GG, Friedman EA, et al. (2011) Genetic variations in the alpha(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine. Circ Cardiovasc Genet 4(2):179–187CrossRefPubMedPubMedCentral Kurnik D, Muszkat M, Li C, Sofowora GG, Friedman EA, et al. (2011) Genetic variations in the alpha(2A)-adrenoreceptor are associated with blood pressure response to the agonist dexmedetomidine. Circ Cardiovasc Genet 4(2):179–187CrossRefPubMedPubMedCentral
15.
go back to reference Oppert JM, Tourville J, Chagnon M, Mauriege P, Dionne FT, et al. (1995) DNA polymorphisms in the alpha 2- and beta 2-adrenoceptor genes and regional fat distribution in humans: association and linkage studies. Obes Res 3(3):249–255CrossRefPubMed Oppert JM, Tourville J, Chagnon M, Mauriege P, Dionne FT, et al. (1995) DNA polymorphisms in the alpha 2- and beta 2-adrenoceptor genes and regional fat distribution in humans: association and linkage studies. Obes Res 3(3):249–255CrossRefPubMed
16.
go back to reference Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Perusse L, et al. (2000) Interactions among the alpha2-, beta2-, and beta3-adrenergic receptor genes and obesity-related phenotypes in the Quebec family study. Metabolism 49(8):1063–1070CrossRefPubMed Ukkola O, Rankinen T, Weisnagel SJ, Sun G, Perusse L, et al. (2000) Interactions among the alpha2-, beta2-, and beta3-adrenergic receptor genes and obesity-related phenotypes in the Quebec family study. Metabolism 49(8):1063–1070CrossRefPubMed
17.
go back to reference Rosengren AH, Jokubka R, Tojjar D, Granhall C, Hansson O, et al. (2010) Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes. Science 327(5962):217–220CrossRefPubMed Rosengren AH, Jokubka R, Tojjar D, Granhall C, Hansson O, et al. (2010) Overexpression of alpha2A-adrenergic receptors contributes to type 2 diabetes. Science 327(5962):217–220CrossRefPubMed
18.
go back to reference Bo S, Cassader M, Cavallo-Perin P, Durazzo M, Rosato R, et al. (2012) The rs553668 polymorphism of the ADRA2A gene predicts the worsening of fasting glucose values in a cohort of subjects without diabetes. A population-based study. Diabet Med 29(4):549–552CrossRefPubMed Bo S, Cassader M, Cavallo-Perin P, Durazzo M, Rosato R, et al. (2012) The rs553668 polymorphism of the ADRA2A gene predicts the worsening of fasting glucose values in a cohort of subjects without diabetes. A population-based study. Diabet Med 29(4):549–552CrossRefPubMed
19.
go back to reference Talmud PJ, Cooper JA, Gaunt T, Holmes MV, Shah S, et al. (2011) Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies. Diabetologia 54(7):1710–1719CrossRefPubMedPubMedCentral Talmud PJ, Cooper JA, Gaunt T, Holmes MV, Shah S, et al. (2011) Variants of ADRA2A are associated with fasting glucose, blood pressure, body mass index and type 2 diabetes risk: meta-analysis of four prospective studies. Diabetologia 54(7):1710–1719CrossRefPubMedPubMedCentral
20.
go back to reference Trentham-Dietz A, Newcomb PA, Storer BE, Longnecker MP, Baron J, et al. (1997) Body size and risk of breast cancer. Am J Epidemiol 145(11):1011–1019CrossRefPubMed Trentham-Dietz A, Newcomb PA, Storer BE, Longnecker MP, Baron J, et al. (1997) Body size and risk of breast cancer. Am J Epidemiol 145(11):1011–1019CrossRefPubMed
21.
go back to reference van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, et al. (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527CrossRefPubMed van den Brandt PA, Spiegelman D, Yaun SS, Adami HO, Beeson L, et al. (2000) Pooled analysis of prospective cohort studies on height, weight, and breast cancer risk. Am J Epidemiol 152(6):514–527CrossRefPubMed
22.
go back to reference Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, et al. (2003) Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95(16):1218–1226CrossRefPubMed Key TJ, Appleby PN, Reeves GK, Roddam A, Dorgan JF, et al. (2003) Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95(16):1218–1226CrossRefPubMed
23.
go back to reference Sinicrope FA, Dannenberg AJ (2011) Obesity and breast cancer prognosis: weight of the evidence. J Clin Oncol 29(1):4–7CrossRefPubMed Sinicrope FA, Dannenberg AJ (2011) Obesity and breast cancer prognosis: weight of the evidence. J Clin Oncol 29(1):4–7CrossRefPubMed
24.
go back to reference DeCensi A, Gennari A (2011) Insulin breast cancer connection: confirmatory data set the stage for better care. J Clin Oncol 29(1):7–10CrossRefPubMed DeCensi A, Gennari A (2011) Insulin breast cancer connection: confirmatory data set the stage for better care. J Clin Oncol 29(1):7–10CrossRefPubMed
25.
go back to reference Vazquez SM, Mladovan AG, Perez C, Bruzzone A, Baldi A, et al. (2006) Human breast cell lines exhibit functional alpha2-adrenoceptors. Cancer Chemother Pharmacol 58(1):50–61CrossRefPubMed Vazquez SM, Mladovan AG, Perez C, Bruzzone A, Baldi A, et al. (2006) Human breast cell lines exhibit functional alpha2-adrenoceptors. Cancer Chemother Pharmacol 58(1):50–61CrossRefPubMed
26.
go back to reference Perez Pinero C, Bruzzone A, Sarappa MG, Castillo LF, Luthy IA (2012) Involvement of alpha2- and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation. Br J Pharmacol 166(2):721–736CrossRefPubMedPubMedCentral Perez Pinero C, Bruzzone A, Sarappa MG, Castillo LF, Luthy IA (2012) Involvement of alpha2- and beta2-adrenoceptors on breast cancer cell proliferation and tumour growth regulation. Br J Pharmacol 166(2):721–736CrossRefPubMedPubMedCentral
27.
go back to reference Vazquez SM, Pignataro O, Luthy IA (1999) Alpha2-adrenergic effect on human breast cancer MCF-7 cells. Breast Cancer Res Treat 55(1):41–49CrossRefPubMed Vazquez SM, Pignataro O, Luthy IA (1999) Alpha2-adrenergic effect on human breast cancer MCF-7 cells. Breast Cancer Res Treat 55(1):41–49CrossRefPubMed
28.
go back to reference Chiesa IJ, Castillo LF, Luthy IA (2008) Contribution of alpha2-adrenoceptors to the mitogenic effect of catecholestrogen in human breast cancer MCF-7 cells. J Steroid Biochem Mol Biol 110(1–2):170–175CrossRefPubMed Chiesa IJ, Castillo LF, Luthy IA (2008) Contribution of alpha2-adrenoceptors to the mitogenic effect of catecholestrogen in human breast cancer MCF-7 cells. J Steroid Biochem Mol Biol 110(1–2):170–175CrossRefPubMed
29.
go back to reference Bruzzone A, Pinero CP, Castillo LF, Sarappa MG, Rojas P, et al. (2008) Alpha2-adrenoceptor action on cell proliferation and mammary tumour growth in mice. Br J Pharmacol 155(4):494–504CrossRefPubMedPubMedCentral Bruzzone A, Pinero CP, Castillo LF, Sarappa MG, Rojas P, et al. (2008) Alpha2-adrenoceptor action on cell proliferation and mammary tumour growth in mice. Br J Pharmacol 155(4):494–504CrossRefPubMedPubMedCentral
30.
go back to reference Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, et al. (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752CrossRefPubMed Perou CM, Sorlie T, Eisen MB, van de Rijn M, Jeffrey SS, et al. (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752CrossRefPubMed
31.
go back to reference Todd JH, Dowle C, Williams MR, Elston CW, Ellis IO, et al. (1987) Confirmation of a prognostic index in primary breast cancer. Br J Cancer 56(4):489–492CrossRefPubMedPubMedCentral Todd JH, Dowle C, Williams MR, Elston CW, Ellis IO, et al. (1987) Confirmation of a prognostic index in primary breast cancer. Br J Cancer 56(4):489–492CrossRefPubMedPubMedCentral
32.
go back to reference Sole X, Guino E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies. Bioinformatics 22(15):1928–1929CrossRefPubMed Sole X, Guino E, Valls J, Iniesta R, Moreno V (2006) SNPStats: a web tool for the analysis of association studies. Bioinformatics 22(15):1928–1929CrossRefPubMed
33.
go back to reference Wirapati P, Sotiriou C, Kunkel S, Farmer P, Pradervand S, et al. (2008) Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res 10(4):R65CrossRefPubMedPubMedCentral Wirapati P, Sotiriou C, Kunkel S, Farmer P, Pradervand S, et al. (2008) Meta-analysis of gene expression profiles in breast cancer: toward a unified understanding of breast cancer subtyping and prognosis signatures. Breast Cancer Res 10(4):R65CrossRefPubMedPubMedCentral
34.
go back to reference El Saghir NS, Seoud M, Khalil MK, Charafeddine M, Salem ZK, et al. (2006) Effects of young age at presentation on survival in breast cancer. BMC Cancer 6:194CrossRefPubMedPubMedCentral El Saghir NS, Seoud M, Khalil MK, Charafeddine M, Salem ZK, et al. (2006) Effects of young age at presentation on survival in breast cancer. BMC Cancer 6:194CrossRefPubMedPubMedCentral
35.
go back to reference Bharat A, Aft RL, Gao F, Margenthaler JA (2009) Patient and tumor characteristics associated with increased mortality in young women (< or =40 years) with breast cancer. J Surg Oncol 100(3):248–251CrossRefPubMed Bharat A, Aft RL, Gao F, Margenthaler JA (2009) Patient and tumor characteristics associated with increased mortality in young women (< or =40 years) with breast cancer. J Surg Oncol 100(3):248–251CrossRefPubMed
37.
go back to reference Le Doussal V, Tubiana-Hulin M, Friedman S, Hacene K, Spyratos F, et al. (1989) Prognostic value of histologic grade nuclear components of scarff-bloom-Richardson (SBR). an improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer 64(9):1914–1921CrossRefPubMed Le Doussal V, Tubiana-Hulin M, Friedman S, Hacene K, Spyratos F, et al. (1989) Prognostic value of histologic grade nuclear components of scarff-bloom-Richardson (SBR). an improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer 64(9):1914–1921CrossRefPubMed
38.
go back to reference Osborne CK, Yochmowitz MG, Knight 3rd WA, McGuire WL (1980) The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 1980 46(12 Suppl):2884–2888 Osborne CK, Yochmowitz MG, Knight 3rd WA, McGuire WL (1980) The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer 1980 46(12 Suppl):2884–2888
39.
go back to reference McGuire WL, Osborne CK, Clark GM, Knight 3rd WA (1982) Steroid hormone receptors and carcinoma of the breast. Am J Phys 243(2):E99–102 McGuire WL, Osborne CK, Clark GM, Knight 3rd WA (1982) Steroid hormone receptors and carcinoma of the breast. Am J Phys 243(2):E99–102
40.
go back to reference Clark GM, McGuire WL (1988) Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol 15(2 Suppl 1):20–25PubMed Clark GM, McGuire WL (1988) Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol 15(2 Suppl 1):20–25PubMed
41.
go back to reference Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, et al. (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182CrossRefPubMed Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, et al. (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235(4785):177–182CrossRefPubMed
42.
go back to reference Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98(19):10869–10874CrossRefPubMedPubMedCentral Sorlie T, Perou CM, Tibshirani R, Aas T, Geisler S, et al. (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98(19):10869–10874CrossRefPubMedPubMedCentral
43.
go back to reference Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, et al. (2009) Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 27(8):1168–1176CrossRefPubMedPubMedCentral Hugh J, Hanson J, Cheang MC, Nielsen TO, Perou CM, et al. (2009) Breast cancer subtypes and response to docetaxel in node-positive breast cancer: use of an immunohistochemical definition in the BCIRG 001 trial. J Clin Oncol 27(8):1168–1176CrossRefPubMedPubMedCentral
44.
go back to reference Boyle DP, McCourt CM, Matchett KB, Salto-Tellez M (2013) Molecular and clinicopathological markers of prognosis in breast cancer. Expert Rev Mol Diagn 13(5):481–498CrossRefPubMed Boyle DP, McCourt CM, Matchett KB, Salto-Tellez M (2013) Molecular and clinicopathological markers of prognosis in breast cancer. Expert Rev Mol Diagn 13(5):481–498CrossRefPubMed
45.
go back to reference Small KM, Brown KM, Seman CA, Theiss CT, Liggett SB (2006) Complex haplotypes derived from noncoding polymorphisms of the intronless alpha2A-adrenergic gene diversify receptor expression. Proc Natl Acad Sci U S A 103(14):5472–5477CrossRefPubMedPubMedCentral Small KM, Brown KM, Seman CA, Theiss CT, Liggett SB (2006) Complex haplotypes derived from noncoding polymorphisms of the intronless alpha2A-adrenergic gene diversify receptor expression. Proc Natl Acad Sci U S A 103(14):5472–5477CrossRefPubMedPubMedCentral
46.
go back to reference Lim E, Vaillant F, Wu D, Forrest NC, Pal B, et al. (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15(8):907–913CrossRefPubMed Lim E, Vaillant F, Wu D, Forrest NC, Pal B, et al. (2009) Aberrant luminal progenitors as the candidate target population for basal tumor development in BRCA1 mutation carriers. Nat Med 15(8):907–913CrossRefPubMed
47.
go back to reference Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, et al. (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14(5):518–527CrossRefPubMed Finak G, Bertos N, Pepin F, Sadekova S, Souleimanova M, et al. (2008) Stromal gene expression predicts clinical outcome in breast cancer. Nat Med 14(5):518–527CrossRefPubMed
48.
go back to reference Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, et al. (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 100(18):10393–10398CrossRefPubMedPubMedCentral Sotiriou C, Neo SY, McShane LM, Korn EL, Long PM, et al. (2003) Breast cancer classification and prognosis based on gene expression profiles from a population-based study. Proc Natl Acad Sci U S A 100(18):10393–10398CrossRefPubMedPubMedCentral
49.
go back to reference Shkurnikov MY, Galatenko VV, Lebedev AE, Podol’skii VE, Tonevitskii EA, et al. (2014) On statistical relationship between ADRA2A expression and the risk of breast cancer relapse. Bull Exp Biol Med 157(4):454–458CrossRefPubMed Shkurnikov MY, Galatenko VV, Lebedev AE, Podol’skii VE, Tonevitskii EA, et al. (2014) On statistical relationship between ADRA2A expression and the risk of breast cancer relapse. Bull Exp Biol Med 157(4):454–458CrossRefPubMed
50.
go back to reference Du Y, Zhou L, Wang Y, Yan T, Jiang Y, et al. (2014) Association of alpha2a and beta2 adrenoceptor expression with clinical outcome in breast cancer. Curr Med Res Opin 30(7):1337–1344CrossRefPubMed Du Y, Zhou L, Wang Y, Yan T, Jiang Y, et al. (2014) Association of alpha2a and beta2 adrenoceptor expression with clinical outcome in breast cancer. Curr Med Res Opin 30(7):1337–1344CrossRefPubMed
51.
go back to reference Lutgendorf SK, Sood AK, Antoni MH (2010) Host factors and cancer progression: biobehavioral signaling pathways and interventions. J Clin Oncol 28(26):4094–4099CrossRefPubMedPubMedCentral Lutgendorf SK, Sood AK, Antoni MH (2010) Host factors and cancer progression: biobehavioral signaling pathways and interventions. J Clin Oncol 28(26):4094–4099CrossRefPubMedPubMedCentral
52.
go back to reference Docherty JR (1998) Subtypes of functional alpha1- and alpha2-adrenoceptors. Eur J Pharmacol 361(1):1–15CrossRefPubMed Docherty JR (1998) Subtypes of functional alpha1- and alpha2-adrenoceptors. Eur J Pharmacol 361(1):1–15CrossRefPubMed
53.
go back to reference Giessler C, Wangemann T, Silber RE, Dhein S, Brodde OE (2002) Noradrenaline-induced contraction of human saphenous vein and human internal mammary artery: involvement of different alpha-adrenoceptor subtypes. Naunyn Schmiedeberg's Arch Pharmacol 366(2):104–109CrossRef Giessler C, Wangemann T, Silber RE, Dhein S, Brodde OE (2002) Noradrenaline-induced contraction of human saphenous vein and human internal mammary artery: involvement of different alpha-adrenoceptor subtypes. Naunyn Schmiedeberg's Arch Pharmacol 366(2):104–109CrossRef
54.
go back to reference Bruckmaier RM, Wellnitz O, Blum JW (1997) Inhibition of milk ejection in cows by oxytocin receptor blockade, alpha-adrenergic receptor stimulation and in unfamiliar surroundings. J Dairy Res 64(3):315–325CrossRefPubMed Bruckmaier RM, Wellnitz O, Blum JW (1997) Inhibition of milk ejection in cows by oxytocin receptor blockade, alpha-adrenergic receptor stimulation and in unfamiliar surroundings. J Dairy Res 64(3):315–325CrossRefPubMed
55.
go back to reference Su F, Ouyang N, Zhu P, Jia W, Gong C, et al. (2005) Psychological stress induces chemoresistance in breast cancer by upregulating mdr1. Biochem Biophys Res Commun 329(3):888–897CrossRefPubMed Su F, Ouyang N, Zhu P, Jia W, Gong C, et al. (2005) Psychological stress induces chemoresistance in breast cancer by upregulating mdr1. Biochem Biophys Res Commun 329(3):888–897CrossRefPubMed
56.
go back to reference Flint MS, Kim G, Hood BL, Bateman NW, Stewart NA, et al. (2009) Stress hormones mediate drug resistance to paclitaxel in human breast cancer cells through a CDK-1-dependent pathway. Psychoneuroendocrinology 34(10):1533–1541CrossRefPubMed Flint MS, Kim G, Hood BL, Bateman NW, Stewart NA, et al. (2009) Stress hormones mediate drug resistance to paclitaxel in human breast cancer cells through a CDK-1-dependent pathway. Psychoneuroendocrinology 34(10):1533–1541CrossRefPubMed
Metadata
Title
ADRA2A Germline Gene Polymorphism is Associated to the Severity, but not to the Risk, of Breast Cancer
Authors
Batoul Kaabi
Ghania Belaaloui
Wassila Benbrahim
Kamel Hamizi
Mourad Sadelaoud
Wided Toumi
Hocine Bounecer
Publication date
01-04-2016
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 2/2016
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-015-0010-0

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