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

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2008 Nov 5

PMID 18980667

Citations 19

Authors

Krisztian Bacsi

Erika Hitre

Janos P Kosa

Henrik Horvath

Aron Lazary

Peter L Lakatos

Bernadett Balla

Barna Budai

Peter Lakatos

Gabor Speer

Affiliations

Soon will be listed here.

Abstract

Background: Epidemiological studies suggested the chemopreventive role of higher calcium intake in colorectal carcinogenesis. We examined genetic polymorphisms that might influence calcium metabolism: lactase (LCT) gene 13910 C/T polymorphism causing lactose intolerance and calcium-sensing receptor (CaSR) gene A986S polymorphism as a responsible factor for the altered cellular calcium sensation.

Methods: 538 Hungarian subjects were studied: 278 patients with colorectal cancer and 260 healthy controls. Median follow-up was 17 months. After genotyping, the relationship between LCT 13910 C/T and CaSR A986S polymorphisms as well as tumor incidence/progression was investigated.

Results: in patient with colorectal cancer, a significantly higher LCT CC frequency was associated with increased distant disease recurrence (OR = 4.04; 95% CI = 1.71-9.58; p = 0.006). The disease free survival calculated from distant recurrence was reduced for those with LCT CC genotype (log rank test p = 0.008). In case of CaSR A986S polymorphism, the homozygous SS genotype was more frequent in patients than in controls (OR = 4.01; 95% CI = 1.33-12.07; p = 0.014). The number of LCT C and CaSR S risk alleles were correlated with tumor incidence (p = 0.035). The CCSS genotype combination was found only in patients with CRC (p = 0.033).

Conclusion: LCT 13910 C/T and CaSR A986S polymorphisms may have an impact on the progression and/or incidence of CRC.

Citing Articles

Calcium intake and genetic variants in the calcium sensing receptor in relation to colorectal cancer mortality: an international consortium study of 18,952 patients.

Wesselink E, Gauderman W, Berndt S, Brenner H, Buchanan D, Campbell P BJC Rep. 2024; 2(1):63.

PMID: 39233917 PMC: 11368808. DOI: 10.1038/s44276-024-00077-3.

Genetically Determined Circulating Lactase/Phlorizin Hydrolase Concentrations and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.

Han S, Yao J, Yamazaki H, Streicher S, Rao J, Nianogo R Nutrients. 2024; 16(6).

PMID: 38542719 PMC: 10975724. DOI: 10.3390/nu16060808.

The Association of Lactose Intolerance With Colon and Gastric Cancers: Friend or Foe?.

Asfari M, Hamid O, Sarmini M, Kendrick K, Pappoppula L, Sifuentes H Cureus. 2022; 14(5):e24713.

PMID: 35676992 PMC: 9166465. DOI: 10.7759/cureus.24713.

CASR rs1801725 polymorphism is associated with the risk and prognosis of colorectal cancer: A case-control study.

Diao Y, Xu Q J Clin Lab Anal. 2020; 34(11):e23463.

PMID: 32648293 PMC: 7676189. DOI: 10.1002/jcla.23463.

Effects of genetic variants on serum parathyroid hormone in hyperparathyroidism and end-stage renal disease patients: A systematic review and meta-analysis.

Matana A, Popovic M, Torlak V, Punda A, Barbalic M, Zemunik T Medicine (Baltimore). 2018; 97(21):e10834.

PMID: 29794776 PMC: 6392899. DOI: 10.1097/MD.0000000000010834.

References

Wong N, Pignatelli M . Beta-catenin--a linchpin in colorectal carcinogenesis?. Am J Pathol. 2002; 160(2):389-401. PMC: 1850660. DOI: 10.1016/s0002-9440(10)64856-0. View

Enattah N, Sahi T, Savilahti E, Terwilliger J, Peltonen L, Jarvela I . Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002; 30(2):233-7. DOI: 10.1038/ng826. View

Chakrabarty S, Radjendirane V, Appelman H, Varani J . 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. 2003; 63(1):67-71. View

Kuokkanen M, Enattah N, Oksanen A, Savilahti E, Orpana A, Jarvela I . Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia. Gut. 2003; 52(5):647-52. PMC: 1773659. DOI: 10.1136/gut.52.5.647. View

Troelsen J, Olsen J, Moller J, Sjostrom H . An upstream polymorphism associated with lactase persistence has increased enhancer activity. Gastroenterology. 2004; 125(6):1686-94. DOI: 10.1053/j.gastro.2003.09.031. View

Obermayer-Pietsch B, Bonelli C, Walter D, Kuhn R, Fahrleitner-Pammer A, Berghold A . Genetic predisposition for adult lactose intolerance and relation to diet, bone density, and bone fractures. J Bone Miner Res. 2004; 19(1):42-7. DOI: 10.1359/JBMR.0301207. View

Lipkin M, Newmark H . Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med. 1985; 313(22):1381-4. DOI: 10.1056/NEJM198511283132203. View

Brown E . Extracellular Ca2+ sensing, regulation of parathyroid cell function, and role of Ca2+ and other ions as extracellular (first) messengers. Physiol Rev. 1991; 71(2):371-411. DOI: 10.1152/physrev.1991.71.2.371. View

Garland C, Garland F, Gorham E . Can colon cancer incidence and death rates be reduced with calcium and vitamin D?. Am J Clin Nutr. 1991; 54(1 Suppl):193S-201S. DOI: 10.1093/ajcn/54.1.193S. View

10.

Lapre J, Termont D, Groen A, van der Meer R . Lytic effects of mixed micelles of fatty acids and bile acids. Am J Physiol. 1992; 263(3 Pt 1):G333-7. DOI: 10.1152/ajpgi.1992.263.3.G333. View

11.

Lapre J, de Vries H, Termont D, Kleibeuker J, De Vries E, van der Meer R . Mechanism of the protective effect of supplemental dietary calcium on cytolytic activity of fecal water. Cancer Res. 1993; 53(2):248-53. View

12.

Campbell B, Finnie I, Hounsell E, Rhodes J . Direct demonstration of increased expression of Thomsen-Friedenreich (TF) antigen in colonic adenocarcinoma and ulcerative colitis mucin and its concealment in normal mucin. J Clin Invest. 1995; 95(2):571-6. PMC: 295516. DOI: 10.1172/JCI117700. View

13.

Garrett J, Capuano I, Hammerland L, Hung B, Brown E, Hebert S . Molecular cloning and functional expression of human parathyroid calcium receptor cDNAs. J Biol Chem. 1995; 270(21):12919-25. DOI: 10.1074/jbc.270.21.12919. View

14.

Lipkin M, Newmark H . Calcium and the prevention of colon cancer. J Cell Biochem Suppl. 1995; 22:65-73. DOI: 10.1002/jcb.240590810. View

15.

Govers M, Termont D, Lapre J, Kleibeuker J, Vonk R, van der Meer R . Calcium in milk products precipitates intestinal fatty acids and secondary bile acids and thus inhibits colonic cytotoxicity in humans. Cancer Res. 1996; 56(14):3270-5. View

16.

Harvey C, Wang Y, Darmoul D, Phillips A, Mantei N, Swallow D . Characterisation of a human homologue of a yeast cell division cycle gene, MCM6, located adjacent to the 5' end of the lactase gene on chromosome 2q21. FEBS Lett. 1996; 398(2-3):135-40. DOI: 10.1016/s0014-5793(96)01189-1. View

17.

Brown E, Pollak M, Hebert S . The extracellular calcium-sensing receptor: its role in health and disease. Annu Rev Med. 1998; 49:15-29. DOI: 10.1146/annurev.med.49.1.15. View

18.

Carroccio A, Montalto G, Cavera G, Notarbatolo A . Lactose intolerance and self-reported milk intolerance: relationship with lactose maldigestion and nutrient intake. Lactase Deficiency Study Group. J Am Coll Nutr. 1998; 17(6):631-6. DOI: 10.1080/07315724.1998.10718813. View

19.

Livak K . Allelic discrimination using fluorogenic probes and the 5' nuclease assay. Genet Anal. 1999; 14(5-6):143-9. DOI: 10.1016/s1050-3862(98)00019-9. View

20.

Chakrabarty S, Wang H, Canaff L, Hendy G, Appelman H, Varani J . Calcium sensing receptor in human colon carcinoma: interaction with Ca(2+) and 1,25-dihydroxyvitamin D(3). Cancer Res. 2005; 65(2):493-8. View