DOI QR코드

DOI QR Code

Parathyroid Hormone Gene rs6256 and Calcium Sensing Receptor Gene rs1801725 Variants are not Associated with Susceptibility to Colorectal Cancer in Iran

  • Mahmoudi, Touraj (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Karimi, Khatoon (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Arkani, Maral (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Farahani, Hamid (Department of Physiology, School of Medicine, Qom University of Medical Sciences) ;
  • Nobakht, Hossein (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Dabiri, Reza (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Asadi, Asadollah (Department of Biology, Faculty of Science, University of Mohaghegh Ardabili) ;
  • Zali, Mohammad Reza (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences)
  • Published : 2014.08.15

Abstract

Background: Substantial evidence from epidemiological studies has suggested that increased levels of calcium may play a protective role against colorectal cancer (CRC). Given the vital role of calcium sensing receptor (CaSR) and parathyroid hormone (PTH) in the maintenance of calcium homeostasis, we explored whether the rs1801725 (A986S) variant located in exon 7 of the CaSR gene and the rs6256 variant located in exon 3 of PTH gene might be associated with CRC risk. Materials and Methods: In this study 860 subjects including 350 cases with CRC and 510 controls were enrolled and genotyped using PCR-RFLP methods. Results: We observed no significant difference in genotype or allele frequencies between the cases with CRC and controls for both CaSR and PTH genes either before or after adjustment for confounding factors including age, BMI, sex, smoking status, and family history of CRC. Furthermore, no evidence for effect modification of any association of rs1801725 and rs6256 variants and CRC by BMI, sex, or tumor site was observed. In addition, there was no significant difference in genotype and allele frequencies between the normal weight (BMI < $25kg/m^2$) cases and overweight/obese (BMI ${\geq}25kg/m^2$) cases for the two SNPs. Conclusions: These data indicated that the CaSR gene A986S variant is not a genetic contributor to CRC risk in the Iranian population. Furthermore, our results suggest for the first time that PTH gene variant does not affect CRC risk. Nonetheless, further studies with larger sample size are needed to validate these findings.

Keywords

References

  1. Bacsi K, Hitre E, Kosa JP, et al (2008). Effects of the lactase 13910 C/T and calcium-sensor receptor A986S G/T gene polymorphisms on the incidence and recurrence of colorectal cancer in Hungarian population. BMC Cancer, 8, 317. https://doi.org/10.1186/1471-2407-8-317
  2. Birchmeier W (1995). E-cadherin as a tumor (invasion) suppressor gene. Bioessays, 17, 97-9. https://doi.org/10.1002/bies.950170203
  3. Buset M, Lipkin M, Winawer S, Swaroop S, Friedman E (1986). Inhibition of human colonic epithelial cell proliferation in vivo and in vitro by calcium. Cancer Res, 46, 5426-30.
  4. Calvo N, Gentili C, de Boland AR (2011). Parathyroid hormone and the regulation of cell cycle in colon adenocarcinoma cells. Biochim Biophys Acta, 1813, 1749-57. https://doi.org/10.1016/j.bbamcr.2011.06.001
  5. Chakrabarty S, Radjendirane V, Appleman H, Varani J (2003). Extracellular calcium and calcium sensing receptor function in human colon carcinomas: promotion of E- cadherin expression and suppression of $\beta$-catenin-TCF activation. Cancer Res, 63, 67-71.
  6. Charalampopoulos A, Charalabopoulos A, Batistatou A, et al (2010). Parathormone and 1,25(OH)2D3 but not 25(OH)D3 serum levels, in an inverse correlation, reveal an association with advanced stages of colorectal cancer. Clin Exp Med, 10, 69-72. https://doi.org/10.1007/s10238-009-0069-6
  7. Cole DE, Peltekova VD, Rubin LA (1999). A986S polymorphism of the calcium-sensing receptor and circulating calcium concentrations. Lancet, 353, 112-5. https://doi.org/10.1016/S0140-6736(98)06434-4
  8. Dong LM, Ulrich CM, Hsu L, et al (2008). Genetic variation in calcium-sensing receptor and risk for colon cancer. Cancer Epidemiol Biomarkers Prev, 17, 2755-65. https://doi.org/10.1158/1055-9965.EPI-08-0388
  9. Fedirko V, Riboli E, Bueno-de-Mesquita HB, et al (2011). Prediagnostic circulating parathyroid hormone concentration and colorectal cancer in the European Prospective Investigation into Cancer and Nutrition cohort. Cancer Epidemiol Biomarkers Prev, 20, 767-78. https://doi.org/10.1158/1055-9965.EPI-10-1212
  10. Ferlay J, Shin HR, 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
  11. Fuszek P, Lakatos P, Tabak A, et al (2004). Relationship between serum calcium and CA 19-9 levels in colorectal cancer. World J Gastroenterol, 10, 1890-2.
  12. Galas A, Augustyniak M, Sochacka-Tatara E (2013). Does dietary calcium interact with dietary fiber against colorectal cancer? A case-control study in Central Europe. Nutr J, 12, 134. https://doi.org/10.1186/1475-2891-12-134
  13. Gama L, Baxendale-Cox LM, Breitwieser GE (1997). $Ca^{2+}$- sensing receptors in intestinal epithelium. Am J Physiol, 273, 1168-75.
  14. Gohda T, Shou I, Fukui M, et al (2002). Parathyroid hormone gene polymorphism and secondary hyperparathyroidism in hemodialysis patients. Am J Kidney Dis, 39, 1255-60. https://doi.org/10.1053/ajkd.2002.33399
  15. Hebert SC, Cheng S, Geibel J (2004). Functions and roles of the extracellular Ca2+ sensing receptor in the gastrointestinal tract. Cell Calcium, 35, 239-47. https://doi.org/10.1016/j.ceca.2003.10.015
  16. Hizaki K, Yamamoto H, Taniguchi H, et al (2011). Epigenetic inactivation of calcium sensing receptor in colorectal carcinogenesis. Modern Pathol, 24, 876-84. https://doi.org/10.1038/modpathol.2011.10
  17. Jenab M, McKay J, Bueno-de-Mesquita HB, et al (2009). Vitamin D receptor and calcium sensing receptor polymorphisms and the risk of colorectal cancer in European populations. Cancer Epidemiol Biomarkers Prev, 18, 2485-91. https://doi.org/10.1158/1055-9965.EPI-09-0319
  18. Kanzawa M, Sugimoto T, Kobayashi T, Kobayashi A, Chihara K (1999). Parathyroid hormone gene polymorphisms in primary hyperparathyroidism. Clin Endocrinol, 50, 583-8. https://doi.org/10.1046/j.1365-2265.1999.00685.x
  19. Kotnis A, Sarin R, Mulherkar R (2005). Genotype, phenotype and cancer: Role of low penetrance genes and environment in tumour susceptibility. J Biosci, 30, 93-102. https://doi.org/10.1007/BF02705154
  20. Lohmueller KE, Pearce CL, Pike M, Lander ES, Hirschhorn JN (2003). Meta-analysis of genetic association studies supports a contribution of common variants to susceptibility to common disease. Nat Genet, 33, 177-182. https://doi.org/10.1038/ng1071
  21. Lusis AJ, Attie AD, Reue K (2008). Metabolic syndrome: from epidemiology to systems biology. Nat Rev Genet, 9, 819-30. https://doi.org/10.1038/nrg2468
  22. Marz W, Seelhorst U, Wellnitz B, et al (2007). Alanine to serine polymorphism at position 986 of the calcium-sensing receptor associated with coronary heart disease, myocardial infarction, all-cause, and cardiovascular mortality. J Clin Endocrinol Metab, 92, 2363-9. https://doi.org/10.1210/jc.2006-0071
  23. Morita M, Yin G, Yoshimitsu S, et al (2013). Folate-related nutrients, genetic polymorphisms, and colorectal cancer risk: the Fukuoka colorectal cancer study. Asian Pac J Cancer Prev, 14, 3561-38. https://doi.org/10.7314/APJCP.2013.14.6.3561
  24. Newmark HL, Wargovich MJ, Bruce WR (1984). Colon cancer and dietary fat, phosphate, and calcium: a hypothesis. J Natl Cancer Inst, 72, 1323-5.
  25. Rogers AC, Hanly AM, Collins D, Baird AW, Winter DC (2012). Review article: loss of the calcium-sensing receptor in colonic epithelium is a key event in the pathogenesis of colon cancer. Clin Colorectal Cancer, 11, 24-30. https://doi.org/10.1016/j.clcc.2011.04.003
  26. Saidak Z, Mentaverri R, Brown EM (2009). The role of the calcium-sensing receptor in the development and progression of cancer. Endocr Rev, 30, 178-95. https://doi.org/10.1210/er.2008-0041
  27. Sarkar P, Kumar S (2012). Calcium sensing receptor modulation for cancer therapy. Asian Pac J Cancer Prev, 13, 3561-38. https://doi.org/10.7314/APJCP.2012.13.8.3561
  28. Sesink AL, Termont DS, Kleibeuker JH, Van der Meer R (2001). Red meat and colon cancer: dietary haem-induced colonic cytotoxicity and epithelial hyperproliferation are inhibited by calcium. Carcinogenesis, 22, 1653-9. https://doi.org/10.1093/carcin/22.10.1653
  29. Sheinin Y, Kallay E, Wrba F, et al (2000). Immunocytochemical localization of the extracellular calcium-sensing receptor in normal and malignant human large intestinal mucosa. J Histochem Cytochem, 48, 595-602. https://doi.org/10.1177/002215540004800503
  30. Speer G, Cseh K, Mucsi K, et al (2002). Calcium-sensing receptor A986S polymorphism in human rectal cancer. Int J Colorectal Dis, 17, 20-4. https://doi.org/10.1007/s003840100359
  31. Varani J (2011). Calcium, calcium-sensing receptor and growth control in the colonic mucosa. Histol Histopathol, 26, 769-79.
  32. Ward BK, Magno AL, Walsh JP, Ratajczak T (2012). The role of the calcium-sensing receptor in human disease. Clin Biochem, 45, 943-53. https://doi.org/10.1016/j.clinbiochem.2012.03.034
  33. Whitfield JF (2009). Calcium, calcium-sensing receptor and colon cancer. Cancer Lett, 275, 9-16. https://doi.org/10.1016/j.canlet.2008.07.001

Cited by

  1. Association between the XRCC3 Thr241Met Polymorphism and Risk of Colorectal Cancer: a Meta Analysis of 5,193 Cases and 6,645 Controls vol.16, pp.6, 2015, https://doi.org/10.7314/APJCP.2015.16.6.2263
  2. The Correlation Between Single Nucleotide Polymorphism Patterns and Colorectal Cancer in the Iranian Population vol.4, pp.3, 2016, https://doi.org/10.17795/acr-41527
  3. Vitamin D receptor and calcium-sensing receptor polymorphisms and colorectal cancer survival in the Newfoundland population vol.117, pp.6, 2017, https://doi.org/10.1038/bjc.2017.242
  4. Voltage-gated calcium channels: Novel targets for cancer therapy vol.14, pp.2, 2017, https://doi.org/10.3892/ol.2017.6457
  5. Calcium-sensing receptor in colorectal inflammation and cancer: Current insights and future perspectives vol.24, pp.36, 2018, https://doi.org/10.3748/wjg.v24.i36.4119