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Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer

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Abstract

The leptin is discharged from breast adipose tissue and is overexpressed in breast cancer (BC). Conflicting relation of leptin with BC was reported. We investigated this association and its impact on leptin level and disease characteristics. The study included 70 females (40 women with pathological proof of invasive BC patients and 30 controls). LEP and LEPR polymorphisms were evaluated by real-time PCR. Serum leptin was estimated by ELISA. Both LEPR and LEP disturbances increase the danger of BC where GG genotype and G allele frequencies of LEPR were higher in patients vs. control. GG genotype increases BC risk with OR (9.1) while G allele predisposes to disease with OR (3.8). Furthermore, LEP A allele was uniquely elevated in patients than healthy ones with OR (2.06). Precise relation of circulating leptin and its polymorphisms with predicting BC may authorize its utilization in early screening.

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References

  1. Alhanafy AM, Tayel S, Ahmed S, Altorgoman A, Elsayed I (2019) Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer. Ann Oncol 30:9. mdz418.012. Meeting Conference Abstract at https://academic.oup.com/annonc/articleabstract/30/Supplement_9/mdz418.012/5638777

    Google Scholar 

  2. Momenimovahed Z, Salehiniya H (2019) Epidemiological characteristics of and risk factors for breast cancer in the world. Breast Cancer (Dove Med Press) 10(11):151–164

    Google Scholar 

  3. Hortobagyi GN, de la Garza Salazar J, Pritchard K, ABREAST Investigators et al (2005) The global breast cancer burden: variations in epidemiology and survival. Clin Breast Cancer 6(5):391–401

    PubMed  Google Scholar 

  4. Ferley J, SoerjomataramI I, Ervik M, Dikshit R, Eser S (2013) GLOBOCAN 2012 v1. 0. Cancer incidence and mortality worldwide: IARC Cancer Base No. 11. International Agency for Research on Cancer, Lyon, France

  5. Ibrahim AS, Khaled HM, Mikhail NN, Baraka H, Kamel H (2014) Cancer incidence in Egypt: results of the national population based cancer registry program. J Cancer Epidemiol 2014:437971

    PubMed  PubMed Central  Google Scholar 

  6. Lo PK, Sukumar S (2008) Epigenomics and breast cancer. Pharmacogenomics 9:1879–1902

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Zhao E, Cui D, Yuan L et al (2012) MDM2 SNP 309 polymorphism and breast cancer risk: a meta-analysis. Mol Biol Rep 39:3471–3477

    CAS  PubMed  Google Scholar 

  8. Carpenter CL, Ross RK, Paganini-Hill A, Bernstein L (2003) Effect of family history, obesity and exercise on breast cancer risk among postmenopausal women. Int J Cancer 106:96–102

    CAS  PubMed  Google Scholar 

  9. Sellahewa C, Nightingale P, Carmichael AR (2008) Obesity and HER 2 overexpression: a common factor for poor prognosis of breast cancer. Int Semin Surg Oncol 5:2

    PubMed  PubMed Central  Google Scholar 

  10. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372(6505):425–432

    CAS  Google Scholar 

  11. Hallaas J, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, Lallone RL, Burley SK, Friedman J (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269:543–546

    Google Scholar 

  12. Benett BD, Solar GP, Yuan JQ, Mathias J, Thomas JR, Matthews W (1996) A role for leptin and its cognate receptor in hematopoiesis. Curr Biol 6:1170–1180

    Google Scholar 

  13. Bouloumie A, Drexler HC, Lafontan M, Busse R (1998) Leptin the product of Ob gene, promotes angiogenesis. Cir Res 269:546–549

    Google Scholar 

  14. Hoggard N, Hunter L, Trayhurn P, Williams LM, Mercer JG (1998) Leptin and reproduction. Proc Nutr Soc 57:421–427

    CAS  PubMed  Google Scholar 

  15. Loffreda S, Yang SQ, Lin HZ, Karp CL, Brengman ML, Wang DJ, Klein AS, Bulkley GB, Bao C, Noble PW, Lane MD, Diehl AM (1998) Leptin regulates proinflammatory immune responses. FASEB J 12:57–65

    CAS  PubMed  Google Scholar 

  16. Green ED, Maffei M, Braden VV, Proenca R, DeSilva U, Zhang Y, Chua SC Jr, Leibel RL, Weissenbach J, Friedman JM (1995) The human obese (OB) gene: RNA expression pattern and mapping on the physical, cytogenetic, and genetic maps of chromosome 7. Genome Res 5:5–12

    CAS  PubMed  Google Scholar 

  17. Hu X, Juneja SC, Maihle NJ, Cleary MP (2002) Leptin—a growth factor in normal and malignant breast cells and for normal mammary gland development. J Natl Cancer Inst 94:1704–1711

    CAS  PubMed  Google Scholar 

  18. Dieudonne MN, Machinal-Quelin F, Serazin-Leroy V, Leneveu MC, Pecquery R, Giudicelli Y (2002) Leptin mediates a proliferative response in human MCF7 breast cancer cells. Biochem Biophys Res Commun 293:622–628

    CAS  PubMed  Google Scholar 

  19. Okumura M, Yamamoto M, Sakuma H, Kojima T, Maruyama T, Jamali M et al (2002) Leptin and high glucose stimulate cell proliferation in MCF-7 human breast cancer cells: reciprocal involvement of PKC-alpha and PPAR expression. Biochim Biophys Acta 1592:107–116

    CAS  PubMed  Google Scholar 

  20. Babaei Z, Moslemi D, Parsian H, Khafri S, Pouramir M et al (2015) Relationship of obesity with serum concentrations of leptin, CRP and IL-6 in breast cancer survivors. J Egypt Natl Cancer Inst 27:223–229

    Google Scholar 

  21. Cleveland RJ, Gammon MD, Long CM, Gaudet MM, Eng SM et al (2010) Common genetic variations in the LEP and LEPR genes, obesity and breast cancer incidence and survival. Breast Cancer Res Treat 120:745–752

    CAS  PubMed  Google Scholar 

  22. Mohammadzadeh G, Ghaffari MA, Bafandeh A, Hosseini SM (2014) Effect of leptin receptor Q223R polymorphism on breast cancer risk. Iran J Basic Med Sci 17:588–594

    PubMed  PubMed Central  Google Scholar 

  23. Mahmoudi R, Alavicheh BN, Mozaffari MAN, Fararouei M, Nikseresht M (2015) Polymorphisms of Leptin (-2548 G/A) and Leptin receptor (Q223R) genes in Iranian women with breast cancer. Int Genomics. https://doi.org/10.1155/2015/132720

    Article  Google Scholar 

  24. Enyioma O, Michael PT, Abd-Ishakur A, Mustapha S, Mona A (2002) Leptin, lipid and lipid metabolism related hormones in chronic renal failure in Arabia. Nephrology 7:115–119

    Google Scholar 

  25. Edge SB, Byrd DR, Compton CC et al (2012) The American Joint Committee on Cancer (AJCC) cancer staging manual, 7th edn. Springer, New York

    Google Scholar 

  26. Baucom DH, Porter LS, Kirby JS, Gremore TM, Keefe FJ (2005) Psychosocial issues confronting young women with breast cancer. Breast Dis 23:103–113

    PubMed  Google Scholar 

  27. Bao B, Wang Z, Li Y, Kong D, Ali S, Banerjee S, Ahmad A, Sarkar FH (2011) The complexities of obesity and diabetes with the development and progression of pancreatic cancer. Biochim Biophys Acta 1815:135–146

    CAS  PubMed  Google Scholar 

  28. Vona-Davis L, Howard-McNatt M, Rose DP (2007) Adiposity, type 2 diabetes and the metabolic syndrome in breast cancer. Obes Rev 8(5):395–408

    CAS  PubMed  Google Scholar 

  29. Andò S, Catalano S (2011) The multifactorial role of leptin in driving the breast cancer microenvironment. Nat Rev Endocrinol 8(5):263–275

    PubMed  Google Scholar 

  30. Riestra P, Garcia-Anguita A, Torres-Cantero A, Bayonas MJ, de Oya M, Garces C (2011) Association of the Q223R polymorphism with age at menarche in the leptin receptor gene in humans. Biol Reprod 84:752–755

    CAS  PubMed  Google Scholar 

  31. Luan H, Zhang H, Li Y, Wang P, Cao L, Ma H, Cui Q, Tian G (2017) Association of two obesity-related gene polymorphisms LEPG2548A rs7799039 and LEPRQ223Rrs1137101 with the risk of breast cancer. Oncotarget 8(35):59333–59344

    PubMed  PubMed Central  Google Scholar 

  32. Yan W, Ma X, Gao X, Zhang S (2016) Association between leptin (2548G/A) genes polymorphism and breast cancer susceptibility: a meta-analysis. Medicine (Baltimore) 95(4):e2566

    CAS  Google Scholar 

  33. Huerta LMG, Cabrera CIS, Montes RM, Cuellar HU, López JT, Covarrubias SAC (2017) Association between leptin and leptin receptor gene polymorphisms and breast cancer risk in premenopausal and postmenopausal Mexican women. Cancer Res Front 3(1):56–63

    Google Scholar 

  34. Snoussi K, Strosberg AD, Bouaouina N, Ben Ahmed S, Helal AN, Chouchane L (2006) Leptin and leptin receptor polymorphisms are associated with increased risk and poor prognosis of breast carcinoma. BMC Cancer 6:38

    PubMed  PubMed Central  Google Scholar 

  35. Woo HY, Park H, Ki CS, Park YL, Bae WG (2006) Relationships among serum leptin, leptin receptor gene polymorphisms, and breast cancer in Korea. Cancer Lett 237(1):137–142

    CAS  PubMed  Google Scholar 

  36. Jarde T, Perrier S, Vasson MP, Caldefie-Chezet F (2011) Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer 47(1):33–43

    CAS  PubMed  Google Scholar 

  37. Gu F, Kraft P, Rice M, Michels KB (2012) Leptin and leptin receptor genes in relation to premenopausal breast cancer incidence and grade in Caucasian women. Breast Cancer Res Treat 131(1):17–25

    CAS  PubMed  Google Scholar 

  38. Cust AE, Stocks T, Lukanova A et al (2009) The influence of overweight and insulin resistance on breast cancer risk and tumour stage at diagnosis: prospective study. Breast Cancer Res Treat 113:567–576

    CAS  PubMed  Google Scholar 

  39. Romero-Figueroa Mdel S, Garduno-Garcia Jde J, Duarte-Mote J et al (2013) Insulin and leptin levels in obese patients with and without breast cancer. Clin Breast Cancer 13:482–485

    PubMed  Google Scholar 

  40. Pan H, Deng L-L, Cui J-Q, Shi L, Yang Y-C, Luo J-H, Qin D, Wang L (2018) Association between serum leptin levels and breast cancer risk. An updated systematic review and meta-analysis. Medicine 97(27):e11345

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Santillán-Benítez J, Quiroz-Ordoñes Á, Mendieta-Zerón H, Gómez-Oliván L (2013) Expresión génica y receptores hormonales en cáncer mamario. “El camino hacia la búsqueda de terapias preventivas”. Revista de Medicina e investigación 1(1):17–24

    Google Scholar 

  42. Bougaret L, Delort L, Billard H, Le Huede C, Boby C, De la Foye A et al (2018) Adipocyte/breast cancer cell crosstalk in obesity interferes with the anti-proliferative efficacy of tamoxifen. PLoS ONE 13(2):e0191571

    PubMed  PubMed Central  Google Scholar 

  43. Linares RL, Benítez JGS, Reynoso MO et al (2019) Modulation of the leptin receptors expression in breast cancer cell lines exposed to leptin and tamoxifen. Sci Rep 9:19189

    CAS  PubMed  Google Scholar 

  44. Guo S, Liu M, Wang G, Torroella-Kouri M, Gonzalez Perez RR (2012) Oncogenic role and therapeutic target of leptin signaling in breast cancer and cancer stem cells. Biochim Biophys Acta 1825:207–222

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Ozet A, Arpaci F, Yilmaz MI, Ayta H, Ozturk B, Komurcu S et al (2001) Effects of tamoxifen on the serum leptin level in patients with breast cancer. Jpn J Clin Oncol 31:424–427

    CAS  PubMed  Google Scholar 

  46. Nyante SJ, Gammon MD, Kaufman JS, Bensen JT, Lin DY, Barnholtz-Sloan JS et al (2011) Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes. Breast Cancer Res Treat 129(2):593–606

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Shi H, Shu H, Huang C, Gong J, Yang Y, Liu R et al (2014) Association of LEPR K109R polymorphisms with cancer risk: a systematic review and pooled analysis. J BUON 19(3):847–854

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt

    Safaa I. Tayel

  2. Clinical Oncology & Nuclear Medicine Department, Faculty of Medicine, Menoufia University, Shebin El-Kom, Menoufia, Egypt

    Alshimaa M. Alhanafy

  3. Chemist at Faculty of Science, Menoufia University, Shebin El-Kom, Menoufia, Egypt

    Solwan M. Ahmed

  4. Organic Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom, Menoufia, Egypt

    Abdelmoneim A. Eltorgoman

  5. Organic and Medicinal Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom, Menoufia, Egypt

    Ibrahim E. Elsayed

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  1. Safaa I. Tayel
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Correspondence to Safaa I. Tayel.

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Safaa Tayel declares that she has no conflict of interest. Alshimaa Alhanafy declares that she has no conflict of interest. Solwan Ahmed declares that she has no conflict of interest. Abdelmoneim Eltorgoman declares that he has no conflict of interest. Ibrahim Elsayed declares that he has no conflict of interest.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Faculty of Medicine, Menoufia University research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Tayel, S.I., Alhanafy, A.M., Ahmed, S.M. et al. Biochemical study on modifying role of variants of leptin gene and its receptor on serum leptin levels in breast cancer. Mol Biol Rep 47, 3807–3820 (2020). https://doi.org/10.1007/s11033-020-05436-0

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  • DOI: https://doi.org/10.1007/s11033-020-05436-0

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