Genetic Variation in CD166 Gene and Its Association with Bladder Cancer Risk in North Indian Population
- 52 Downloads
Abstract
Adhesion molecules play a key role in cancer progression and tumorigenesis. Genetic polymorphism of adhesion molecules may alter the normal functioning thereby leading to bladder cancer susceptibility. Hence we aimed to evaluate three SNPs of CD166 gene (CD166rs6437585 C/T, CD166rs10511244 C/T, and CD166rs1157 A/G) in bladder cancer patients and normal controls of North Indian population. A total of 270 healthy controls and 240 confirmed bladder cancer patients were recruited for this study. Three SNPs of CD166 gene viz. CD166rs6437585 C/T, CD166rs10511244 C/T, and CD166rs1157 A/G were selected for this study. CD166rs6437585 C/T and CD166rs10511244 C/T were genotyped by Taqman allelic discrimination assay and CD166rs1157 A/G was genotyped by PCR–RFLP. The statistical analysis was done using the SPSS software, version 16.0 (SPSS, Chicago, IL), and p < 0.05 was considered statistically significant. Haplotypic analysis was done by using SNP analyzer version 1.2A. CD166rs6437585 C/T and CD166rs10511244 C/T showed significant association with reduced risk in bladder cancer while CD166rs1157 A/G showed significant high risk along with association at genotypic and allelic levels. Haplotypic analysis showed 1.8-folds risk in CCG combination, whereas CTA and TCG showed significant association with reduced risk. Further stratification on the basis of smoking, tumor grade/stage and BGC therapy revealed no association of these three polymorphic sites of CD166. Our study suggests that CD166rs6437585 C/T and CD166rs10511244 C/T are predictive for the reduced risk of bladder cancer, whereas CD166rs1157 A/G had shown significant association with high risk of bladder cancer in North Indians. This somehow suggests that CD166rs1157 A/G can be used as a marker for risk prediction of bladder cancer.
Keywords
CD166 gene (ALCAM) Bladder cancer PCR–RFLP BCG immunotherapyNotes
Acknowledgments
This study was funded by Department of Science and Technology (DST) [SR/SO/HS-120/2007], New Delhi. The assistance of relevant clinical information of the patients by the Urologists and Pathologists are duly acknowledged.
Compliance with Ethical Standards
Conflict of interest
Authors have no conflicts of interest in this work.
References
- 1.American Cancer Society. Cancer facts and figures 2015. Atlanta: American Cancer Society; 2015.Google Scholar
- 2.Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013. http://globocan.iarc.fr. Accessed Dec 2013.
- 3.Murthy NS, Nandakumar BS, Pruthvish S, George PS, Mathew A. Disability adjusted life years for cancer patients in India. Asian Pac J Cancer Prev. 2010;11(3):633–40.PubMedGoogle Scholar
- 4.Kitamura H, Okudela K, Yazawa T, Sato H, Shimoyamada H. Cancer stem cell: implications in cancer biology and therapy with special reference to lung cancer. Lung Cancer. 2009;66(3):275–81. doi: 10.1016/j.lungcan.2009.07.019.CrossRefPubMedGoogle Scholar
- 5.Eramo A, Haas TL, De Maria R. Lung cancer stem cells: tools and targets to fight lung cancer. Oncogene. 2010;29(33):4625–35. doi: 10.1038/onc.2010.207.CrossRefPubMedGoogle Scholar
- 6.Ni C, Zhang Z, Zhu X, Liu Y, Qu D, Wu P, et al. Prognostic value of CD166 expression in cancers of the digestive system: a systematic review and meta-analysis. PLoS ONE. 2013;8(8):e70958. doi: 10.1371/journal.pone.0070958.CrossRefPubMedPubMedCentralGoogle Scholar
- 7.Dalerba P, Dylla SJ, Park IK, Liu R, Wang X, Cho RW, et al. Phenotypic characterization of human colorectal cancer stem cells. Proc Natl Acad Sci USA. 2007;104(24):10158–63.CrossRefPubMedPubMedCentralGoogle Scholar
- 8.Vermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K, Perez Alea M, et al. Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA. 2008;105(36):13427–32. doi: 10.1073/pnas.0805706105.CrossRefPubMedPubMedCentralGoogle Scholar
- 9.Levin TG, Powell AE, Davies PS, Silk AD, Dismuke AD, Anderson EC, Swain JR, Wong MH. Characterization of the intestinal cancer stem cell marker CD166 in the human and mouse gastrointestinal tract. Gastroenterology. 2010;139(6):2072–82.e5.doi: 10.1053/j.gastro.2010.08.053.CrossRefPubMedPubMedCentralGoogle Scholar
- 10.Jiao J, Hindoyan A, Wang S, Tran LM, Goldstein AS, Lawson D, et al. Identification of CD166 as a surface marker for enriching prostate stem/progenitor and cancer initiating cells. PLoS ONE. 2012;7(8):e42564. doi: 10.1371/journal.pone.0042564.CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.CrossRefPubMedGoogle Scholar
- 12.Tachezy M, Zander H, Wolters-Eisfeld G, Müller J, Wicklein D, Gebauer F, et al. Activated leukocyte cell adhesion molecule (CD166): an “inert” cancer stem cell marker for non-small cell lung cancer? Stem Cells. 2014;32(6):1429–36.CrossRefPubMedGoogle Scholar
- 13.Clauditz TS, von Rheinbaben K, Lebok P, Minner S, Tachezy M, Borgmann K, et al. Activated leukocyte cell adhesion molecule (ALCAM/CD166) expression in head and neck squamous cell carcinoma (HNSSC). Pathol Res Pract. 2014;2010(10):649–55.CrossRefGoogle Scholar
- 14.Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55(2):74–108.CrossRefPubMedGoogle Scholar
- 15.Zhou P, Du LF, Lv GQ, Yu XM, Gu YL, Li JP, et al. Functional polymorphisms in CD166/ALCAM gene associated with increased risk for breast cancer in a Chinese population. Breast Cancer Res Treat. 2011;128(2):527–34.CrossRefPubMedGoogle Scholar
- 16.Yadav A, Gupta A, Rastogi N, Agrawal S, Kumar A, Kumar V, Mittal B. Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival. Tumour Biol. 2016;37(2):1835–44.CrossRefPubMedGoogle Scholar
- 17.Varadi V, Bevier M, Grzybowska E, Johansson R, Enquist-Olsson K, Henriksson R, et al. Genetic variation in ALCAM and other chromosomal instability genes in breast cancer survival. Breast Cancer Res Treat. 2012;131(1):311–9.CrossRefPubMedGoogle Scholar
- 18.Gerger A, Zhang W, Yang D, Bohanes P, Ning Y, Winder T, et al. Common cancer stem cell gene variants predict colon cancer recurrence. Clin Cancer Res. 2011;17(21):6934–43.CrossRefPubMedGoogle Scholar
- 19.Zhang K, Civan J, Mukherjee S, Patel F, Yang H. Genetic variations in colorectal cancer risk and clinical outcome. World J Gastroenterol. 2014;20(15):4167–77.CrossRefPubMedPubMedCentralGoogle Scholar
- 20.Colombel M, Soloway M, Akaza H, Böhle A, Palou J, Buckley R, Lamm D, Brausi M, Witjes JA, Persad R. Epidemiology, staging, grading and risk stratification of bladder cancer. Eur Urol Suppl. 2008;7(10):618–26.CrossRefGoogle Scholar
- 21.Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988;16:1215.CrossRefPubMedPubMedCentralGoogle Scholar
- 22.Jiang WG, Puntis MC, Hallett MB. Molecular and cellular basis of cancer invasion and metastasis: implications for treatment. Br J Surg. 1994;81(11):1576–90.CrossRefPubMedGoogle Scholar
- 23.Kristiansen G, Pilarsky C, Wissmann C, Stephan C, Weissbach L, Loy V, et al. ALCAM/CD166 is up-regulated in low-grade prostate cancer and progressively lost in high-grade lesions. Prostate. 2003;54(1):34–43.CrossRefPubMedGoogle Scholar
- 24.Van Kempen LC, Meier F, Egeblad M, Kersten-Niessen MJ, Garbe C, Weidle UH, et al. Truncation of activated leukocyte cell adhesion molecule: a gateway to melanoma metastasis. J Investig Dermatol. 2004;122(5):1293–301.CrossRefPubMedGoogle Scholar
- 25.Verma A, Shukla NK, Deo SV, Gupta SD, Ralhan R. MEMD/ALCAM: a potential marker for tumor invasion and nodal metastasis in esophageal squamous cell carcinoma. Oncology. 2005;68(4–6):462–70.CrossRefPubMedGoogle Scholar
- 26.Ihnen M, Kress K, Kersten JF, Kilic E, Choschzick M, Zander H, et al. Relevance of activated leukocyte cell adhesion molecule (ALCAM) in tumor tissue and sera of cervical cancer patients. BMC Cancer. 2012;4(12):140.CrossRefGoogle Scholar
- 27.Weichert W, Knösel T, Bellach J, Dietel M, Kristiansen G. ALCAM/CD166 is overexpressed in colorectal carcinoma and correlates with shortened patient survival. J Clin Pathol. 2004;57(11):1160–4.CrossRefPubMedPubMedCentralGoogle Scholar
- 28.Chappell PE, Garner LI, Yan J, Metcalfe C, Hatherley D, Johnson S, Robinson V, Lea SM, Brown MH. Structures of CD6 and its ligand CD166 give insight into their interaction. Structure. 2015;23(8):1426–36.CrossRefPubMedPubMedCentralGoogle Scholar