Table of Contents Author Guidelines Submit a Manuscript
International Journal of Endocrinology
Volume 2015, Article ID 173218, 8 pages
http://dx.doi.org/10.1155/2015/173218
Research Article

Polymorphism in LEP and LEPR May Modify Leptin Levels and Represent Risk Factors for Thyroid Cancer

1Laboratory of Cancer Molecular Genetics (Gemoca), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Rua Tessalia Vieira de Camargo 126, 13083-970 Campinas, SP, Brazil
2Laboratory of Investigation on Metabolism and Diabetes (LIMED), Faculty of Medical Sciences, University of Campinas (FCM-Unicamp), Rua Carlos Chagas 420, 13083-878 Campinas, SP, Brazil
3Service of Nuclear Medicine, University of Campinas, Rua Vital Brasil 251, 13083-888 Campinas, SP, Brazil
4Service of Endocrinology, University of Campinas, Rua Vital Brasil 251, 13083-888 Campinas, SP, Brazil
5Department of Head and Neck Surgery, Barretos Cancer Hospital, Rua Antenor Duarte Vilela 1331, 14784-400 Barretos, SP, Brazil

Received 6 January 2015; Accepted 13 February 2015

Academic Editor: Giuseppe Damante

Copyright © 2015 Marjory Alana Marcello et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. P. Cheng, C. W. Chi, C. Y. Tzen et al., “Clinicopathologic significance of leptin and leptin receptor expressions in papillary thyroid carcinoma,” Surgery, vol. 147, no. 6, pp. 847–853, 2010. View at Publisher · View at Google Scholar
  2. K. Y. Wolin, K. Carson, and G. A. Colditz, “Obesity and cancer,” The Oncologist, vol. 15, no. 6, pp. 556–565, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. F. Osorio-Costa, G. Z. Rocha, M. M. Dias, and J. B. Carvalheira, “Epidemiological and molecular mechanisms aspects linking obesity and cancer,” Arquivos Brasileiros de Endocrinologia & Metabologia, vol. 53, no. 2, pp. 213–226, 2009. View at Publisher · View at Google Scholar
  4. M. A. Marcello, L. L. Cunha, F. A. Batista, and L. S. Ward, “Obesity and thyroid cancer,” Endocrine-Related Cancer, vol. 21, no. 5, pp. T255–T271, 2014. View at Publisher · View at Google Scholar
  5. A. B. Negrão and J. Licinio, “Leptina: o diálogo entre adipócitos e neurônios,” Arquivos Brasileiros de Endocrinologia & Metabologia, vol. 44, no. 3, pp. 205–214, 2000. View at Publisher · View at Google Scholar
  6. B. N. Finck and R. W. Johnson, “Tumor necrosis factor-alpha regulates secretion of the adipocyte-derived cytokine, leptin,” Microscopy Research and Technique, vol. 50, no. 3, pp. 209–215, 2000. View at Publisher · View at Google Scholar
  7. W.-L. Liao, C.-C. Chen, C.-T. Chang et al., “Gene polymorphisms of adiponectin and leptin receptor are associated with early onset of type 2 diabetes mellitus in the Taiwanese population,” International Journal of Obesity, vol. 36, no. 6, pp. 790–796, 2012. View at Publisher · View at Google Scholar · View at Scopus
  8. Z. Yu, S. Han, X. Cao, C. Zhu, X. Wang, and X. Guo, “Genetic polymorphisms in adipokine genes and the risk of obesity: a systematic review and meta-analysis,” Obesity, vol. 20, no. 2, pp. 396–406, 2012. View at Publisher · View at Google Scholar
  9. J. He and G. Xu, “LEP gene variant is associated with prostate cancer but not with colorectal cancer,” Tumor Biology, vol. 34, no. 5, pp. 3131–3136, 2013. View at Publisher · View at Google Scholar
  10. C. Dallal, S. Garte, C. Ragin et al., “Plasma leptin levels, LEPR Q223R polymorphism and mammographic breast density: a cross-sectional study,” The International Journal of Biological Markers, vol. 28, no. 2, pp. 161–167, 2013. View at Publisher · View at Google Scholar · View at Scopus
  11. L.-Q. Wang, W. Shen, L. Xu et al., “The association between polymorphisms in the leptin receptor gene and risk of breast cancer: a systematic review and pooled analysis,” Breast Cancer Research and Treatment, vol. 136, no. 1, pp. 231–239, 2012. View at Publisher · View at Google Scholar · View at Scopus
  12. E.-Y. Kim, H.-M. Chin, S.-M. Park et al., “Susceptibility of gastric cancer according to leptin and leptin receptor gene polymorphisms in Korea,” Journal of the Korean Surgical Society, vol. 83, no. 1, pp. 7–13, 2012. View at Publisher · View at Google Scholar · View at Scopus
  13. Y. Li, J. Geng, Y. Wang et al., “The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients,” Journal of Cancer Research and Clinical Oncology, vol. 138, no. 2, pp. 311–316, 2012. View at Publisher · View at Google Scholar · View at Scopus
  14. N. E. Bufalo, J. L. Leite, A. C. T. Guilhen et al., “Smoking and susceptibility to thyroid cancer: an inverse association with CYP1A1 allelic variants,” Endocrine-Related Cancer, vol. 13, no. 4, pp. 1185–1193, 2006. View at Publisher · View at Google Scholar · View at Scopus
  15. L. Xu, E. C. Morari, Q. Wei, E. M. Sturgis, and L. S. Ward, “Functional variations in the ATM gene and susceptibility to differentiated thyroid carcinoma,” The Journal of Clinical Endocrinology & Metabolism, vol. 97, no. 6, pp. 1913–1921, 2012. View at Publisher · View at Google Scholar
  16. J. F. M. de Almeida, W. G. Tsumura, M. Vaisman, L. V. M. Assumpção, and L. S. Ward, “Current recommendations for levothyroxine treatment of differentiated thyroid cancer patients are not properly implemented in a clinical practice,” Journal of Endocrinological Investigation, vol. 35, no. 10, pp. 901–904, 2012. View at Publisher · View at Google Scholar · View at Scopus
  17. M. A. Marcello, A. C. Sampaio, B. Geloneze, A. C. J. Vasques, L. V. M. Assumpção, and L. S. Ward, “Obesity and excess protein and carbohydrate consumption are risk factors for thyroid cancer,” Nutrition and Cancer, vol. 64, no. 8, pp. 1190–1195, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. WHO, “Obesity and overweight,” 2012, http://www.who.int/mediacentre/factsheets/fs311/en/index.html.
  19. D. S. Cooper, G. M. Doherty, B. R. Haugen et al., “Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer,” Thyroid, vol. 19, no. 11, pp. 1167–1214, 2009. View at Publisher · View at Google Scholar · View at Scopus
  20. F. Pitoia, L. Ward, N. Wohllk et al., “Recommendations of the Latin American Thyroid Society on diagnosis and management of differentiated thyroid cancer,” Arquivos Brasileiros de Endocrinologia e Metabologia, vol. 53, no. 7, pp. 884–887, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. R. Camargo, S. Corigliano, C. Friguglietti et al., “Latin American thyroid society recommendations for the management of thyroid nodules,” Arquivos Brasileiros de Endocrinologia& Metabologia, vol. 53, no. 9, pp. 1167–1175, 2009. View at Publisher · View at Google Scholar · View at Scopus
  22. M. L. M. P. Jorge, V. N. de Oliveira, N. M. Resende et al., “The effects of aerobic, resistance, and combined exercise on metabolic control, inflammatory markers, adipocytokines, and muscle insulin signaling in patients with type 2 diabetes mellitus,” Metabolism: Clinical and Experimental, vol. 60, no. 9, pp. 1244–1252, 2011. View at Publisher · View at Google Scholar · View at Scopus
  23. A. F. Godoy-Matos, L. R. Bahia, R. C. Domingues et al., “Adiponectin is related to intramyocellular lipid content in non-diabetic adults,” Journal of Endocrinological Investigation, vol. 33, no. 6, pp. 382–387, 2010. View at Publisher · View at Google Scholar · View at Scopus
  24. B. Geloneze, J. A. Pereira, J. C. Pareja et al., “Overcoming metabolic syndrome in severe obesity: adiponectin as a marker of insulin sensitivity and HDL-cholesterol improvements after gastric bypass,” Arquivos Brasileiros de Endocrinologia e Metabologia, vol. 53, no. 2, pp. 293–300, 2009. View at Publisher · View at Google Scholar · View at Scopus
  25. M. L. Slattery, R. K. Wolff, J. Herrick, B. J. Caan, and J. D. Potter, “Leptin and leptin receptor genotypes and colon cancer: gene-gene and gene-lifestyle interactions,” International Journal of Cancer, vol. 122, no. 7, pp. 1611–1617, 2008. View at Publisher · View at Google Scholar · View at Scopus
  26. M. García-Bermúdez, C. González-Juanatey, L. Rodríguez-Rodríguez et al., “Lack of association between LEP rs2167270 (19 G>A) polymorphism and disease susceptibility and cardiovascular disease in patients with rheumatoid arthritis,” Clinical and Experimental Rheumatology, vol. 29, no. 2, pp. 293–298, 2011. View at Google Scholar · View at Scopus
  27. Y. Jiang, J. B. Wilk, I. Borecki et al., “Common variants in the 5′ region of the leptin gene are associated with body mass index in men from the National Heart, Lung, and Blood Institute Family Heart Study,” The American Journal of Human Genetics, vol. 75, no. 2, pp. 220–230, 2004. View at Publisher · View at Google Scholar · View at Scopus
  28. J. He, B. Xi, R. Ruiter et al., “Association of LEP G2548A and LEPR Q223R polymorphisms with cancer susceptibility: evidence from a meta-analysis,” PLoS ONE, vol. 8, no. 10, Article ID e75135, 2013. View at Publisher · View at Google Scholar · View at Scopus
  29. T. Furusawa, I. Naka, T. Yamauchi et al., “The Q223R polymorphism in LEPR is associated with obesity in Pacific Islanders,” Human Genetics, vol. 127, no. 3, pp. 287–294, 2010. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Saukko, Y. A. Kesäniemi, and O. Ukkola, “Leptin receptor Lys109Arg and Gln223Arg polymorphisms are associated with early atherosclerosis,” Metabolic Syndrome and Related Disorders, vol. 8, no. 5, pp. 425–430, 2010. View at Publisher · View at Google Scholar · View at Scopus
  31. A. Lucas, M. L. Granada, I. Olaizola et al., “Leptin and thyrotropin relationship is modulated by smoking status in euthyroid subjects,” Thyroid, vol. 23, no. 8, pp. 964–970, 2013. View at Publisher · View at Google Scholar · View at Scopus
  32. L. H. Duntas and B. Biondi, “The interconnections between obesity, thyroid function, and autoimmunity: the multifold role of leptin,” Thyroid, vol. 23, no. 6, pp. 646–653, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. P. Marzullo, A. Minocci, M. A. Tagliaferri et al., “Investigations of thyroid hormones and antibodies in obesity: leptin levels are associated with thyroid autoimmunity independent of bioanthropometric, hormonal, and weight-related determinants,” Journal of Clinical Endocrinology and Metabolism, vol. 95, no. 8, pp. 3965–3972, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. S. Guzel, A. Seven, E. C. Guzel, B. Buyuk, A. Celebi, and B. Aydemir, “Visfatin, leptin, and TNF-α: interrelated adipokines in insulin-resistant clinical and subclinical hypothyroidism,” Endocrine Research, vol. 38, no. 3, pp. 184–194, 2013. View at Publisher · View at Google Scholar · View at Scopus
  35. O. Mammès, D. Betoulle, R. Aubert, B. Herbeth, G. Siest, and F. Fumeron, “Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight,” Annals of Human Genetics, vol. 64, no. 5, pp. 391–394, 2000. View at Publisher · View at Google Scholar · View at Scopus
  36. O. Portoles, J. V. Sorli, F. Frances et al., “Effect of genetic variation in the leptin gene promoter and the leptin receptor gene on obesity risk in a population-based case-control study in Spain,” European Journal of Epidemiology, vol. 21, no. 8, pp. 605–612, 2006. View at Publisher · View at Google Scholar
  37. C. Liu and L. Liu, “Polymorphisms in three obesity-related genes (LEP, LEPR, and PON1) and breast cancer risk: a meta-analysis,” Tumour Biology, vol. 32, no. 6, pp. 1233–1240, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Hoffsted, P. Eriksson, S. Mottagui-Tabar, and P. Arner, “A polymorphism in the leptin promoter region (-2548 G/A) influences gene expression and adipose tissue secretion of leptin,” Hormone and Metabolic Research, vol. 34, no. 7, pp. 355–359, 2002. View at Publisher · View at Google Scholar · View at Scopus
  39. D. Murugesan, T. Arunachalam, V. Ramamurthy, and S. Subramanian, “Association of polymorphisms in leptin receptor gene with obesity and type 2 diabetes in the local population of Coimbatore,” Indian Journal of Human Genetics, vol. 16, no. 2, pp. 72–77, 2010. View at Publisher · View at Google Scholar
  40. N. D. Quinton, A. J. Lee, R. J. M. Ross, R. Eastell, and A. I. F. Blakemore, “A single nucleotide polymorphism (SNP) in the leptin receptor is associated with BMI, fat mass and leptin levels in postmenopausal Caucasian women,” Human Genetics, vol. 108, no. 3, pp. 233–236, 2001. View at Publisher · View at Google Scholar · View at Scopus
  41. V. S. Mattevi, V. M. Zembrzuski, and M. H. Hutz, “Association analysis of genes involved in the leptin-signaling pathway with obesity in Brazil,” International Journal of Obesity, vol. 26, no. 9, pp. 1179–1185, 2002. View at Publisher · View at Google Scholar · View at Scopus
  42. N. Yiannakouris, M. Yannakoulia, L. Melistas, J. L. Chan, D. Klimis-Zacas, and C. S. Mantzoros, “The Q223R polymorphism of the leptin receptor gene is significantly associated with obesity and predicts a small percentage of body weight and body composition variability,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 9, pp. 4434–4439, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. N. Stefan, B. Vozarova, A. Del Parigi et al., “The Gln223Arg polymorphism of the leptin receptor in Pima Indians: influence on energy expenditure, physical activity and lipid metabolism,” International Journal of Obesity, vol. 26, no. 12, pp. 1629–1632, 2002. View at Publisher · View at Google Scholar · View at Scopus
  44. K. C. Chiu, A. Chu, L.-M. Chuang, and M. F. Saad, “Association of leptin receptor polymorphism with insulin resistance,” European Journal of Endocrinology, vol. 150, no. 5, pp. 725–729, 2004. View at Publisher · View at Google Scholar · View at Scopus
  45. A. Chu, L. M. Chuang, M. Saad, and K. Chiu, “Association of the Q223R polymorphism of the leptin receptor gene with insulin resistance and metabolic syndrome,” Diabetes, vol. 52, p. A510, 2003. View at Google Scholar
  46. S. F. Pimentel Duarte, E. A. Francischetti, V. Genelhu-Abreu et al., “p.Q223R leptin receptor polymorphism associated with obesity in Brazilian multiethnic subjects,” The American Journal of Human Biology, vol. 18, no. 4, pp. 448–453, 2006. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Wauters, I. Mertens, M. Chagnon et al., “Polymorphisms in the leptin receptor gene, body composition and fat distribution in overweight and obese women,” International Journal of Obesity, vol. 25, no. 5, pp. 714–720, 2001. View at Publisher · View at Google Scholar · View at Scopus
  48. T. Ogawa, H. Hirose, Y. Yamamoto et al., “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: Clinical and Experimental, vol. 53, no. 7, pp. 879–885, 2004. View at Publisher · View at Google Scholar · View at Scopus
  49. U. L. Fairbrother, L. B. Tankó, A. J. Walley, C. Christiansen, P. Froguel, and A. I. F. Blakemore, “Leptin receptor genotype at Gln223Arg is associated with body composition, BMD, and vertebral fracture in postmenopausal Danish women,” Journal of Bone and Mineral Research, vol. 22, no. 4, pp. 544–550, 2007. View at Publisher · View at Google Scholar · View at Scopus
  50. T. Salopuro, L. Pulkkinen, J. Lindström et al., “Genetic variation in leptin receptor gene is associated with type 2 diabetes and body weight: the Finnish Diabetes Prevention Study,” International Journal of Obesity, vol. 29, no. 10, pp. 1245–1251, 2005. View at Publisher · View at Google Scholar · View at Scopus
  51. M. Wauters, I. Mertens, T. Rankinen, M. Chagnon, C. Bouchardt, and L. van Gaal, “Leptin receptor gene polymorphisms are associated with insulin in obese women with impaired glucose tolerance,” Journal of Clinical Endocrinology and Metabolism, vol. 86, no. 7, pp. 3227–3232, 2001. View at Publisher · View at Google Scholar · View at Scopus
  52. K. S. Park, H. D. Shin, B. L. Park, and et al, “Polymorphisms in the leptin receptor (LEPR)—putative association with obesity and T2DM,” Journal of Human Genetics, vol. 51, no. 2, pp. 85–91, 2006. View at Publisher · View at Google Scholar · View at Scopus
  53. C.-Z. Han, L.-L. Du, J.-X. Jing et al., “Associations among lipids, leptin, and leptin receptor gene Gin223Arg polymorphisms and breast cancer in China,” Biological Trace Element Research, vol. 126, no. 1–3, pp. 38–48, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. M. N. Okobia, C. H. Bunker, S. J. Garte et al., “Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: a case control study,” BMC Cancer, vol. 8, article 338, 2008. View at Publisher · View at Google Scholar · View at Scopus
  55. B.-S. He, Y.-Q. Pan, Y. Zhang, Y.-Q. Xu, and S.-K. Wang, “Effect of LEPR Gln223Arg polymorphism on breast cancer risk in different ethnic populations: a meta-analysis,” Molecular Biology Reports, vol. 39, no. 3, pp. 3117–3122, 2012. View at Publisher · View at Google Scholar · View at Scopus
  56. D. W. Lin, L. M. FitzGerald, R. Fu et al., “Genetic variants in the LEPR, CRY1, RNASEL, IL4, and ARVCF genes are prognostic markers of prostate cancer-specific mortality,” Cancer Epidemiology, Biomarkers & Prevention, vol. 20, no. 9, pp. 1928–1936, 2011. View at Publisher · View at Google Scholar · View at Scopus
  57. Y. L. Li, J. L. Geng, Y. Wang et al., “The role of leptin receptor gene polymorphisms in determining the susceptibility and prognosis of NSCLC in Chinese patients,” Journal of Cancer Research and Clinical Oncology, vol. 138, no. 2, pp. 311–316, 2012. View at Publisher · View at Google Scholar · View at Scopus
  58. U. Wazir, W. Al Sarakbi, W. G. Jiang, and K. Mokbel, “Evidence of an autocrine role for leptin and leptin receptor in human breast cancer,” Cancer Genomics and Proteomics, vol. 9, no. 6, pp. 383–388, 2012. View at Google Scholar · View at Scopus
  59. L. Li, K. J. Lee, B. C. Choi, and K. H. Baek, “Relationship between leptin receptor and polycystic ovary syndrome,” Gene, vol. 527, no. 1, pp. 71–74, 2013. View at Publisher · View at Google Scholar
  60. Y. Friedlander, G. Li, M. Fornage et al., “Candidate molecular pathway genes related to appetite regulatory neural network, adipocyte homeostasis and obesity: results from the CARDIA Study,” Annals of Human Genetics, vol. 74, no. 5, pp. 387–398, 2010. View at Publisher · View at Google Scholar · View at Scopus