Advertisement

Molecular and Cellular Biochemistry

, Volume 448, Issue 1–2, pp 137–144 | Cite as

Leptin receptor gene (A/G) polymorphism rs1137101 and renal cell carcinoma

  • Azza M. Abdu Allah
  • Sally M. El-HefnwayEmail author
  • Alshimaa M. Alhanafy
  • Ahmed M. Zahran
  • Heba E. Kasem
Article

Abstract

Leptin plays an important role in carcinogenesis as leptin/leptin receptor signaling promotes the angiogenesis, proliferation, and inhibits epithelial cell apoptosis. Variants in the leptin receptor gene have potential associations with renal cell carcinoma (RCC). We aimed to investigate association of rs1137101 (A/G) polymorphism at LEPR gene with risk of RCC and patients survival. 123 individuals were classified into group I: 73 RCC patients and group II: 50 healthy controls. Genotyping of the Gln223Arg (A/G) polymorphism rs1137101 at LEPR gene was analyzed using allelic discrimination assay by Real-Time PCR technique. GG genotype was the most frequent among RCC patients (67.1%), while AA genotype was the most frequent in controls (60%); (p < 0.001). By univariate cox regression: gene polymorphism (GG versus GA +AA), stage, histopathologic subtype, and grade were found to affect survival significantly; however, the multivariate analysis showed that only gene polymorphism (GG versus GA +AA) and tumor stage significantly affect survival. LEPR gene variants rs1137101 might be a candidate risk factor for RCC in Egypt. GG genotype is associated with more aggressive tumor behavior and shorter survival compared with GA & AA genotypes so, genotyping of Gln223Arg (A/G) rs1137101 could also predict RCC outcome.

Keywords

Gene Leptin Polymorphism Receptor 

Notes

Acknowledgements

We acknowledge all patients and controls participated in the current study, also many thanks to DR. Eman Abd Al-Fattah (Central Laboratory Manager) and all members of central laboratory at faculty of medicine, menaufia University for facilitating real-time PCR step.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

References

  1. 1.
    Siegel RL, Miller KD, Jemal A (2017) Cancer statistics, 2017. CA Cancer J Clin 67:7CrossRefGoogle Scholar
  2. 2.
    Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J et al (2013) Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer 49:1374CrossRefGoogle Scholar
  3. 3.
    Ibrahim AS, Khaled HM, Mikhail NH et al (2014) Cancer incidence in Egypt: results of the national population-based cancer registry program. J Cancer Epidemiol 2014:18CrossRefGoogle Scholar
  4. 4.
    Ghosn M, Jaloudi M, Larbaoui B et al (2015) Insights into the epidemiology of renal cell carcinoma in North Africa and the Middle East Pan Arab. J Oncol 8(2):38–43Google Scholar
  5. 5.
    Sun M et al (2013) Management of localized kidney cancer: calculating cancer-specific mortality and competing-risks of death tradeoffs between surgery and active surveillance. J Urol 189:e672CrossRefGoogle Scholar
  6. 6.
    Masson-Lecomte A et al (2013) A prospective comparison of the pathologic and surgical outcomes obtained after elective treatment of renal cell carcinoma by open or robot-assisted partial nephrectomy. Urol Oncol 31:924CrossRefGoogle Scholar
  7. 7.
    Choi JE et al (2015) Comparison of perioperative outcomes between robotic and laparoscopic partial nephrectomy: a systematic review and meta-analysis. Eur Urol 67:891CrossRefGoogle Scholar
  8. 8.
    Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. (2008) Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet 371:569–578CrossRefGoogle Scholar
  9. 9.
    Tilg H, Moschen A (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6:772–783CrossRefGoogle Scholar
  10. 10.
    Wauman J, Tavernier J (2011) Leptin receptor signaling: pathways to leptin resistance. Front Biosci 17:2771–2793CrossRefGoogle Scholar
  11. 11.
    Unsal M, Kara N, Karakus N, Sengul T, Elbistan M (2014) :Effects of leptin and leptin receptor gene polymorphisms on lung cancer. Tumor Biol 35:10231–10236CrossRefGoogle Scholar
  12. 12.
    Wang LQ, Shen W, Xu L et al (2012) The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis. Breast Cancer Res Treat 136:231–239CrossRefGoogle Scholar
  13. 13.
    Dallal C, Garte S, Ragin C et al (2013) Plasma leptin levels, LEPR Q223R polymorphism and mammographic breast density: a cross-sectional study. Int J Biol Markers 28:161–167CrossRefGoogle Scholar
  14. 14.
    Drew JE (2012) Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin. Proc Nutr Soc 71:175–180CrossRefGoogle Scholar
  15. 15.
    Liu L, Zhong R, Wei S et al (2013) The leptin gene family and colorectal cancer: interaction with smoking behavior and family history of cancer. PLoS ONE 8:60777CrossRefGoogle Scholar
  16. 16.
    Kim EY, Chin HM, Park SM et al (2012) Susceptibility of gastric cancer according to leptin and leptin receptor gene polymorphisms in Korea. J Korean Surg Soc 83:7–13CrossRefGoogle Scholar
  17. 17.
    Li Y, Geng J, Wang Y et al (2012) The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients. J Cancer Res Clin Oncol 138:311–316CrossRefGoogle Scholar
  18. 18.
    Yapijakis C, Kechagiadakis M, Nkenke E et al (2009) Association of leptin-2548G/A and leptin receptor Q223R polymorphisms with increased risk for oral cancer. J Cancer Res Clin Oncol 135:603–612CrossRefGoogle Scholar
  19. 19.
    Mu H, Zou J, Xie P, Xu Z, Ruan J, Yang S, Yin Y (2014) Leptin receptor Lys109Arg and Gln223Arg polymorphisms and risk of clear cell RCC. Asian Pac J Cancer Prev 15(10):4211–4215CrossRefGoogle Scholar
  20. 20.
    Motzer RJ, Jonasch E, Bhyani S et al (2018): NCCN clinical practice guidelines in oncology (NCCN guidelines) kidney cancer version 2.2018Google Scholar
  21. 21.
    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 7:115–119CrossRefGoogle Scholar
  22. 22.
    Edge SB, Byrd DR, Compton CC et al (eds) (2012) The American Joint Committee on Cancer (AJCC) cancer staging manual, 7th edn. Springer, New YorkGoogle Scholar
  23. 23.
    Dutta D, Ghosh S, Pandit K, Mukhopadhyay P, Chowdhury S (2012) Leptin and cancer: pathogenesis and modulation. Indian J Endocrinol Metab 16(Suppl 3):S596–S600PubMedPubMedCentralGoogle Scholar
  24. 24.
    Ptak A, Kolaczkowska E, Gregoraszczuk EL (2013) Leptin stimulation of cell cycle and inhibition of apoptosis gene and protein expression in OVCAR-3 ovarian cancer cells. Endocrine 43:394–403CrossRefGoogle Scholar
  25. 25.
    Margetic S, Gazzola C, Pegg GG, Hill RA (2002) Leptin: a review of its peripheral actions and interactions. Int J Obes Relat Metab Disord 26(11):1407–1433CrossRefGoogle Scholar
  26. 26.
    Fairbrother UL, Tank_o LB, Walley AJ, Christiansen C, Froguel P, Blakemore AI (2007) Leptin receptor genotype at Gln223 Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women. J Bone Miner Res 22:544–550CrossRefGoogle Scholar
  27. 27.
    Ogawa T, Hirose H, Yamamoto Y, Nishikai K, Miyashita K, Nakamura H et al (2004) Relationships between serum soluble leptin receptor level and serum leptin and adiponectin levels, insulin resistance index, lipid profile, and leptin receptor gene polymorphisms in the Japanese population. Metabolism 53:879–885CrossRefGoogle Scholar
  28. 28.
    Hastuti p, Zukhrufia I, Padwaswari M, Nuraini A, Sadewa A (2016) Polymorphism in leptin receptor gene was associated with obesity in Yogyakarta, Indonesia. Egypt J Med Hum Genet 17:271–276CrossRefGoogle Scholar
  29. 29.
    Duarte SFP, Francischetti EA, Genelhu-Abreu V, Barroso SG, Braga JU, Cabello PH et al (2006).p.Q223R leptin receptor polymorphism associated with obesity in Brazilian multiethnic subjects. Am J Hum Biol 18:448–453CrossRefGoogle Scholar
  30. 30.
    Stefan N, Vozarova B, Del Parigi A et al (2002) The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism. Int J Obes Relat Metab Disord 26:1629–1632CrossRefGoogle Scholar
  31. 31.
    Huerta L, Cabrera C, Montes R, Cuellar H, López J, Covarrubias S (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.  https://doi.org/10.17980/2017.56 CrossRefGoogle Scholar
  32. 32.
    Anuradha C, Madanranjit P, Surekha D, Raghunadharao D et al (2012) association of leptin receptor (LEPR) Q223R polymorphism with breast cancer. Glob J Med Res 12:1–11Google Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Azza M. Abdu Allah
    • 1
  • Sally M. El-Hefnway
    • 1
    Email author
  • Alshimaa M. Alhanafy
    • 2
  • Ahmed M. Zahran
    • 3
  • Heba E. Kasem
    • 3
  1. 1.Medical Biochemistry, Faculty of MedicineMenoufia UniversityMenoufiaEgypt
  2. 2.Clinical Oncology & Nuclear Medicine, Faculty of MedicineMenoufia UniversityMenoufiaEgypt
  3. 3.Nephrology Unite of Internal Medicine, Faculty of MedicineMenoufia UniversityMenoufiaEgypt

Personalised recommendations