Lack of Association between the CDH1 -160C>A Polymorphism and Risk of Gastrointestinal Cancer - a Meta-Analysis

  • Sahami-Fard, Mohammad Hossein (Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, International Campus) ;
  • Yazd, Ehsan Farashahi (Department of Genetics, Shahid Sadoughi University of Medical Sciences) ;
  • Khazaei, Zahra (Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, International Campus) ;
  • Neamatzadeh, Hossein (Hematology and Oncology Research Center, Shahid Sadoughi University of Medical Sciences)
  • Published : 2016.05.01


E-cadherin (CDH1) genetic variations alter gene transcriptional activity of epithelial cells in vitro and may cause susceptibility to various cancers. Associations of CDH1 -160C>A polymorphism with various cancers have been widely reported. However, the results are controversial and inconsistent. To derive a more accurate estimation of the relationship, a meta-analysis was performed with regard to gastrointestinal (GI) cancer risk. Eligible studies were identified through a search of PubMed database until December 2015. Associations between the CDH1 -160C>A polymorphism and GI cancer risk was considered by odds ratios (ORs) together with their 95% confidence intervals (CIs). A total of 31 studies including 11,606 cases and 12,655 controls were involved in this meta-analysis. Overall, this meta-analysis showed no association between CDH1 -160C>A polymorphism and GI cancer risk (A vs. C: OR = 1.08, 95%CI = 0.98-1.18, P = 0.086;CA vs. CC: OR = 1.09, 95%CI = 0.97-1.22, P = 0.118; AA vs. CC: OR = 1.10, 95%CI = 0.89-1.35, P = 0.356; AA vs. CC + CA: OR = 1.06, 95%CI = 0.96-1.18, P = 0.207; CA+AA vs. CC: OR = 1.01, 95%CI = 0.84-1.22, P = 0.89). In subgroup analysis, similar results were found. In conclusion, this meta-analysis has demonstrated that there is a lack of association of the CDH1-160C>A polymorphism with GI cancer susceptibility.


  1. Agiostratidou G, Muros RM, Shioi J, et al (2006). The cytoplasmic sequence of E-cadherin promotes nonamyloidogenic degradation of A beta precursors. J Neurochem, 96, 1182-8.
  2. Al-Moundhri MS, Al-Khanbashi M, Al-Kindi M, et al (2010). Association of E-cadherin (CDH1) gene polymorphisms and gastric cancer risk. World J Gastroenterol, 16, 3432-6.
  3. Borges Bdo N, Santos Eda S, Bastos CE, et al (2010). Promoter polymorphisms and methylation of E-cadherin (CDH1) and KIT in gastric cancer patients from northern Brazil. Anticancer Res, 30, 2225-33.
  4. Breier G, Grosser M, Rezaei M (2014). Endothelial cadherins in cancer. Cell Tissue Res, 355, 523-7.
  5. Carney PA, O'Malley JP, Gough A, et al (2013). Association between documented family history of cancer and screening for breast and colorectal cancer. Prev Med, 57, 679-84.
  6. Cattaneo F, Venesio T, Molatore S, et al (2006). Functional analysis and case-control study of -160C/A polymorphism in the E-cadherin gene promoter: association with cancer risk. Anticancer Res, 26, 4627-32.
  7. Chu CM, Chen CJ, Chan DC, et al (2014). CDH1 polymorphisms and haplotypes in sporadic diffuse and intestinal gastric cancer: a case-control study based on direct sequencing analysis. World J Surg Oncol, 12, 80.
  8. Corso G, Berardi A, Marrelli D, et al (2009). CDH1 C-160A promoter polymorphism and gastric cancer risk. Eur J Cancer Prev, 18, 46-9.
  9. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  10. Govatati S, Singamsetty GK, Nallabelli N, et al (2014). Contribution of cyclin D1 (CCND1) and E-cadherin (CDH1) alterations to colorectal cancer susceptibility: a case-control study. Tumour Biol, 35, 12059-67.
  11. Grunhage F, Jungck M, Lamberti C, et al (2008). Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes. Int J Colorectal Dis, 23, 147-54.
  12. Hansen RD, Sorensen M, Tjonneland A, et al (2007). XPA A23G, XPC Lys939Gln, XPD Lys751Gln and XPD Asp312Asn polymorphisms, interactions with smoking, alcohol and dietary factors, and risk of colorectal cancer. Mutat Res, 619, 68-80.
  13. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21, 1539-58.
  14. Humar B, Toro T, Graziano F, et al (2002). Novel germline CDH1 mutations in hereditary diffuse gastric cancer families. Hum Mutat, 19, 518-25.
  15. Jenab M, McKay JD, Ferrari P, et al (2008). CDH1 gene polymorphisms, smoking, Helicobacter pylori infection and the risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC-EURGAST). Eur J Cancer, 44, 774-80.
  16. Kuraoka K, Oue N, Yokozaki H, et al (2003). Correlation of a single nucleotide polymorphism in the E-cadherin gene promoter with tumorigenesis and progression of gastric carcinoma in Japan. Int J Oncol, 23, 421-7.
  17. Li LC, Chui RM, Sasaki M, et al (2000). A single nucleotide polymorphism in the E-cadherin gene promoter alters transcriptional activities. Cancer Res, 60, 873-6.
  18. Lu Y, Xu YC, Shen J, et al (2005). E-cadherin gene C-160A promoter polymorphism and risk of non-cardia gastric cancer in a Chinese population. World J Gastroenterol, 11, 56-60.
  19. Medina-Franco H, Ramos-De la Medina A, Vizcaino G, et al (2007). Single nucleotide polymorphisms in the promoter region of the E-cadherin gene in gastric cancer: case-control study in a young Mexican population. Ann Surg Oncol, 14, 2246-9.
  20. Nakamura A, Shimazaki T, Kaneko K, et al (2002). Characterization of DNA polymorphisms in the E-cadherin gene (CDH1) promoter region. Mutat Res, 502, 19-24.
  21. Nakayama KI, Nakayama K (2006). Ubiquitin ligases: cell-cycle control and cancer. Nat Rev Cancer, 6, 369-81.
  22. Park WS, Cho YG, Park JY, et al (2003). A single nucleotide polymorphism in the E-cadherin gene promoter-160 is not associated with risk of Korean gastric cancer. J Korean Med Sci,18, 501-4.
  23. Pharoah PD, Oliveira C, Machado JC, et al (2002). CDH1 c-160a promotor polymorphism is not associated with risk of stomach cancer. Int J Cancer, 101, 196-7.
  24. Pittman AM, Twiss P, Broderick P, et al (2009). The CDH1-160C>A polymorphism is a risk factor for colorectal cancer. Int J Cancer, 125, 1622-5.
  25. Porter TR, Richards FM, Houlston RS, et al (2002). Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. Oncogene, 21, 1928-33.
  26. Shapiro L, Weis WI (2009). Structure and Biochemistry of Cadherins and Catenins. Cold Spring Harb Perspect Biol, 1.
  27. Shin Y, Kim IJ, Kang HC, et al (2004). A functional polymorphism (-347 G-->GA) in the E-cadherin gene is associated with colorectal cancer. Carcinogenesis, 25, 2173-6.
  28. Siegel R, Naishadham D, Jemal A (2012). Cancer statistics, 2012. CA Cancer J Clin, 62, 10-29.
  29. Song CG, Huang CM, Liu X, et al (2005). [Association of -160 (C-->A) polymorphism in CDH1 gene with gastric cancer risk in Fujian Chinese population]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 22, 557-9.
  30. Song F, Khan KS, Dinnes J, et al (2002). Asymmetric funnel plots and publication bias in meta-analyses of diagnostic accuracy. Int J Epidemiol, 31, 88-95.
  31. Tan XL, Nieters A, Kropp S, et al (2008). The association of cyclin D1 G870A and E-cadherin C-160A polymorphisms with the risk of colorectal cancer in a case control study and meta-analysis. Int J Cancer, 122, 2573-80.
  32. Torre LA, Bray F, Siegel RL, et al (2015). Global cancer statistics, 2012. CA Cancer J Clin, 65, 87-108.
  33. Vasioukhin V (2012). Adherens junctions and cancer. Subcell Biochem, 60, 379-414.
  34. Vincent PA, Xiao K, Buckley KM, et al (2004). VE-cadherin: adhesion at arm's length. Am J Physiol Cell Physiol, 286, 987-97.
  35. Wu MS, Huang SP, Chang YT, et al (2002). Association of the -160 C --> a promoter polymorphism of E-cadherin gene with gastric carcinoma risk. Cancer, 94, 1443-8.
  36. Xiong H, Hong J, Du W, et al (2012). Roles of STAT3 and ZEB1 proteins in E-cadherin down-regulation and human colorectal cancer epithelial-mesenchymal transition. J Biol Chem, 287, 5819-32.
  37. Yamada H, Shinmura K, Ikeda S, et al (2007). Association between CDH1 haplotypes and gastric cancer risk in a Japanese population. Scand J Gastroenterol, 42, 1479-85.
  38. Yamada T ADea 2009. Textbook of gastroenterology (5th ed.), Chichester, West Sussex: Blackwell Pub.
  39. Zhan Z, Wu J, Zhang JF, et al (2012). CDH1 gene polymorphisms, plasma CDH1 levels and risk of gastric cancer in a Chinese population. Mol Biol Rep, 39, 8107-13.
  40. Zhang B, Pan K, Liu Z, et al (2008a). Genetic polymorphisms of the E-cadherin promoter and risk of sporadic gastric carcinoma in Chinese populations. Cancer Epidemiol Biomarkers Prev, 17, 2402-8.
  41. Zhang XF, Wang YM, Ge H, et al (2008b). Association of CDH1 single nucleotide polymorphisms with susceptibility to esophageal squamous cell carcinomas and gastric cardia carcinomas. Dis Esophagus, 21, 21-9.
  42. Zou XP, Dai WJ, Cao J (2009). CDH1 promoter polymorphism (-347G-->GA) is a possible prognostic factor in sporadic colorectal cancer. World J Gastroenterol, 15, 5340-5.