DOI QR코드

DOI QR Code

Association of Leptin Receptor Lys109Arg and Gln223Arg Polymorphisms with Increased Risk of Clear Cell Renal Cell Carcinoma

  • Mu, Hui-Jun (Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University) ;
  • Zou, Jian (Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University) ;
  • Xie, Ping (Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University) ;
  • Xu, Zhuo-Qun (Department of Urinary Surgery, Wuxi People's Hospital of Nanjing Medical University) ;
  • Ruan, Jun (Department of Urinary Surgery, Wuxi People's Hospital of Nanjing Medical University) ;
  • Yang, Shu-Dong (Department of Pathology, Wuxi People's Hospital of Nanjing Medical University) ;
  • Yin, Ying (Department of Clinical Laboratory Science, Wuxi People's Hospital of Nanjing Medical University)
  • Published : 2014.05.30

Abstract

Background: Although roles of genetic polymorphisms of leptin receptor (LEPR) gene in several cancers have been documented, the association between polymorphisms of LEPR and clear cell renal cell carcinoma (CC-RCC) remains unknown. The aim of this study was to explore any relation. Materials and Methods: The study population consisted of 77 patients with CC-RCC and 161 healthy control subjects. Polymorphism analyses of Lys109Arg and Gln223Arg were performed by direct DNA sequencing and PCR-restriction fragment length polymorphism approaches respectively. Results: Comparisons of allelic and genotypic frequencies in Lys109Arg and Gln223Arg showed no significant difference between the cases and controls. However, when evaluating the combined genotype of Lys109Arg and Gln223Arg, risk with GG/GG was increased (OR=1.85, 95%CI=1.04-3.30) and with GA/GG or GG/GA was decreased (OR=0.07, 95%CI=0.01-0.54; OR and 95%CI of the latter could not be calculated for a value of zero). Furthermore, the G-G haplotype frequency of Lys109Arg and Gln223Arg in the cases was higher (OR=1.68; 95%CI=1.02-2.76). In contrast, the A-G and G-A haplotype frequencies in the cases were lower than those in the controls (OR=0.06; 95%CI=0.01 to 0.47; OR and 95%CI of the latter could not be calculated for a value of zero). In addition, the Lys109Arg A allele was in LD with the Gln223Arg A allele (d'=0.9399) in the CC-RCC subjects, but not in the controls. Conclusions: Our data suggest that the GG/GG combined genotype and G-G haplotype of Lys109Arg and Gln223Arg can act as evaluating factors for CC-RCC risk.

Keywords

References

  1. Alegre M M, Knowles M H, Robison R A, et al (2013). Mechanics behind breast cancer prevention - focus on obesity, exercise and dietary fat. Asian Pac J Cancer Prev, 14, 2207-12. https://doi.org/10.7314/APJCP.2013.14.4.2207
  2. 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, 161-7. https://doi.org/10.5301/jbm.5000016
  3. Drew J E (2012). Molecular mechanisms linking adipokines to obesity-related colon cancer: focus on leptin. Proc Nutr Soc, 71, 175-80. https://doi.org/10.1017/S0029665111003259
  4. Excoffier L, Lischer H E (2010). Arlequin suite ver 3.5: a new series of programs to perform population genetics analyses under Linux and Windows. Mol Ecol Resour, 10, 564-7. https://doi.org/10.1111/j.1755-0998.2010.02847.x
  5. Ferlay J, Shin H R, Bray F, et al (2010). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917. https://doi.org/10.1002/ijc.25516
  6. Fruhbeck G. (2006). Intracellular signalling pathways activated by leptin. Biochem J, 393, 7-20. https://doi.org/10.1042/BJ20051578
  7. Han C Z, Du L L, Jing J X, et al (2008). Associations among lipids, leptin, and leptin receptor gene Gin223Arg polymorphisms and breast cancer in China. Biol Trace Elem Res, 126, 38-48. https://doi.org/10.1007/s12011-008-8182-z
  8. Horiguchi A, Sumitomo M, Asakuma J, et al (2006a). Increased serum leptin levels and over expression of leptin receptors are associated with the invasion and progression of renal cell carcinoma. J Urol, 176, 1631-5. https://doi.org/10.1016/j.juro.2006.06.039
  9. Horiguchi A, Sumitomo M, Asakuma J, et al (2006b). Leptin promotes invasiveness of murine renal cancer cells via extracellular signal-regulated kinases and rho dependent pathway. J Urol, 176, 1636-41. https://doi.org/10.1016/j.juro.2006.06.040
  10. Jarde T, Perrier S, Vasson M P, et al (2011). Molecular mechanisms of leptin and adiponectin in breast cancer. Eur J Cancer, 47, 33-43. https://doi.org/10.1016/j.ejca.2010.09.005
  11. Kim E Y, Chin, H M, Park S M, et al (2012). Susceptibility of gastric cancer according to leptin and leptin receptor gene polymorphisms in Korea. J Korean Surg Soc, 83, 7-13. https://doi.org/10.4174/jkss.2012.83.1.7
  12. Kovacs G, Akhtar M, Beckwith B J, et al (1997). The Heidelberg classification of renal cell tumours. J Pathol, 183, 131-3. https://doi.org/10.1002/(SICI)1096-9896(199710)183:2<131::AID-PATH931>3.0.CO;2-G
  13. Li L, Gao Y, Zhang L L, et al (2008). Concomitant activation of the JAK/STAT3 and ERK1/2 signaling is involved in leptinmediated proliferation of renal cell carcinoma Caki-2 cells. Cancer Biol Ther, 7, 1787-92. https://doi.org/10.4161/cbt.7.11.6837
  14. 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, 311-6. https://doi.org/10.1007/s00432-011-1098-6
  15. Liu C L, Chang Y C, Cheng S P, et al (2007). The roles of serum leptin concentration and polymorphism in leptin receptor gene at codon 109 in breast cancer. Oncology, 72, 75-81. https://doi.org/10.1159/000111097
  16. 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, 60777. https://doi.org/10.1371/journal.pone.0060777
  17. Nyante S J, Gammon M D, Kaufman J S, et al (2011). Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes. Breast Cancer Res Treat, 129, 593-606. https://doi.org/10.1007/s10549-011-1517-z
  18. Oswal A, Yeo G (2010). Leptin and the control of body weight: a review of its diverse central targets, signaling mechanisms, and role in the pathogenesis of obesity. Obesity, 18, 221-9. https://doi.org/10.1038/oby.2009.228
  19. Paracchini V, Pedotti P, Taioli E (2005). Genetics of leptin and obesity: a HuGE review. Am J Epidemiol, 162, 101-14. https://doi.org/10.1093/aje/kwi174
  20. Ptak A, Kolaczkowska E, Gregoraszczuk E L (2013). Leptin stimulation of cell cycle and inhibition of apoptosis gene and protein expression in OVCAR-3 ovarian cancer cells. Endocrine, 43, 394-403. https://doi.org/10.1007/s12020-012-9788-7
  21. Samuel-Mendelsohn S, Inbar M, Weiss-Messer E, et al (2011). Leptin signaling and apoptotic effects in human prostate cancer cell lines. Prostate, 71, 929-45. https://doi.org/10.1002/pros.21309
  22. Shimizu H, Mori M (2001). Role of leptin and its receptor in the regulation of appetite and body fat. Nihon Rinsho, 59, 421-6 (in Japanese).
  23. 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, 1629-32. https://doi.org/10.1038/sj.ijo.0802161
  24. Teras L R, Goodman M, Patel A V, et al (2009). No association between polymorphisms in LEP, LEPR, ADIPOQ, ADIPOR1, or ADIPOR2 and postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev, 18, 2553-7. https://doi.org/10.1158/1055-9965.EPI-09-0542
  25. Wang L Q, 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, 231-9. https://doi.org/10.1007/s10549-012-2228-9
  26. Wauman J, Tavernier J (2011). Leptin receptor signaling: pathways to leptin resistance. Front Biosci, 17, 2771-93.
  27. Woo H Y, Park H, Ki C S, et al (2006). Relationships among serum leptin, leptin receptor gene polymorphisms, and breast cancer in Korea. Cancer Lett, 237, 137-42. https://doi.org/10.1016/j.canlet.2005.05.041
  28. Wu N, Wang Y, Wang S, et al (2013). Recombinant human leptin induces growth inhibition and apoptosis in human gastric cancer MGC-803 cells. Clin Exp Med, 13, 305-14. https://doi.org/10.1007/s10238-012-0211-8
  29. 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, 603-12. https://doi.org/10.1007/s00432-008-0494-z
  30. Yuan Y, Zhang J, Cai L, et al (2013). Leptin induces cell proliferation and reduces cell apoptosis by activating c-myc in cervical cancer. Oncol Rep, 29, 2291-6.
  31. Zhang Y, Proenca R, Maffei M, et al (1994). Positional cloning of the mouse obese gene and its human homologue. Nature, 372, 425-32. https://doi.org/10.1038/372425a0
  32. Zhou W, Guo S, Gonzalez-Perez R R (2011). Leptin proangiogenic signature in breast cancer is linked to IL-1 signalling. Br J Cancer, 104, 128-37. https://doi.org/10.1038/sj.bjc.6606013

Cited by

  1. Predictive value of vascular endothelial growth factor polymorphisms on the clinical outcome of renal cell carcinoma patients pp.1792-1082, 2015, https://doi.org/10.3892/ol.2014.2798
  2. Associations of Probiotics with Vitamin D and Leptin Receptors and their Effects on Colon Cancer vol.16, pp.9, 2015, https://doi.org/10.7314/APJCP.2015.16.9.3621
  3. Predictive value of vascular endothelial growth factor polymorphisms on the risk of renal cell carcinomas: a case–control study vol.36, pp.11, 2015, https://doi.org/10.1007/s13277-015-3431-1
  4. Lack of association variants of leptin and leptin receptor gene and OSAHS in Chinese Han population vol.14, pp.1, 2016, https://doi.org/10.1007/s41105-015-0022-x
  5. Leptin receptor gene (A/G) polymorphism rs1137101 and renal cell carcinoma vol.448, pp.1-2, 2018, https://doi.org/10.1007/s11010-018-3320-1