Roles of E-Cadherin (CDH1) Genetic Variations in Cancer Risk: a Meta-analysis

  • Deng, Qi-Wen (Central Laboratory, Nanjing First Hospital, Nanjing Medical University) ;
  • He, Bang-Shun (Central Laboratory, Nanjing First Hospital, Nanjing Medical University) ;
  • Pan, Yu-Qin (Central Laboratory, Nanjing First Hospital, Nanjing Medical University) ;
  • Sun, Hui-Ling (Department of Life Sciences, Nanjing Normal University) ;
  • Xu, Ye-Qiong (Central Laboratory, Nanjing First Hospital, Nanjing Medical University) ;
  • Gao, Tian-Yi (Central Laboratory, Nanjing First Hospital, Nanjing Medical University) ;
  • Li, Rui (Department of Life Sciences, Nanjing Normal University) ;
  • Song, Guo-Qi (Central Laboratory, Nanjing First Hospital, Nanjing Medical University) ;
  • Wang, Shu-Kui (Central Laboratory, Nanjing First Hospital, Nanjing Medical University)
  • Published : 2014.04.30


E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis of various cancers by altering gene transcriptional activity of epithelial cells. However, published studies on the association of CDH1 gene polymorphisms and cancer risk remain contradictory, owing to differences in living habits and genetic backgrounds. To derive a more better and comprehensive conclusion, the present meta-analysis was performed including 57 eligible studies of the association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and 3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, -160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with the homozygotes (CC), and the similar result was discovered for the -160A allele in the overall analyses. In the subgroup analyses, obvious elevated risk was found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate cancer, while a decreased colorectal cancer risk was shown with the AA genotype. For the -347 G>GA polymorphism, the GAGA genotype was associated with increased cancer risk in the overall analysis with homozygous and recessive models. In addition, results of subgroup analysis indicated that the elevated risks were observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a decreased risk of cancer was found in heterozygous, dominant and allele models. Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a potential protective factor in gastric cancer and Asian descendants.


Supported by : National Nature Science Foundation of China


  1. 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.
  2. Yamada H, Shinmura K, Ikeda S, et al. (2007). Association betweenCDH1haplotypes and gastric cancer risk in a Japanese population. Scand J Gastroenterol, 42, 1479-85.
  3. 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.
  4. Zhang XF, Wang YM, Ge H, et al (2007). Association of CDH1 single nucleotide polymorphisms with susceptibility to esophageal squamous cell carcinomas and gastric cardia carcinomas. Dis Esophagus, 21, 21-9.
  5. Shin Y, Kim IJ, Kang HC, et al (2004). The E-cadherin -347G->GA promoter polymorphism and its effect on transcriptional regulation. Carcinogenesis, 25, 895-9.
  6. Takeichi M. (1991). Cadherin cell adhesion receptors as a morphogenetic regulator. Science, 251, 1451-5.
  7. Tamgue O, Chai CS, Hao L, et al (2013). Triptolide inhibits histone methyltransferase EZH2 and modulates the expression of its target genes in prostate cancer cells. Asian Pac J Cancer Prev, 14, 5663-9.
  8. Tipirisetti NR, Govatati S, Govatati S, et al (2013). Association of E-cadherin single-nucleotide polymorphisms with the increased risk of breast cancer: a study in South Indian women. Genet Test Mol Biomarkers, 17, 494-500.
  9. Tsukino H, Kuroda Y, Imai H, et al (2004). Lack of evidence for the association of E-cadherin gene polymorphism with increased risk or progression of prostate cancer. Urol Int, 72, 203-7.
  10. Wang YX, Zhao L, Wang XY, et al (2011). Association between E-cadherin (CDH1) polymorphisms and papillary thyroid carcinoma risk in Han Chinese population. Endocrine, 41, 526-31.
  11. Wang Y, Yang H, Li L, et al. (2011). E-cadherin (CDH1) gene promoter polymorphism and the risk of colorectal cancer. Int J Colorectal Dis, 27, 151-8.
  12. 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.
  13. Pittman AM, Twiss P, Broderick P, et al (2009). TheCDH1-160C>A polymorphism is a risk factor for colorectal cancer. Int J Cancer, 125, 1622-5.
  14. 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.
  15. Pecina-Slaus N (2003). Tumor suppressor gene E-cadherin and its role in normal and malignant cells. Cancer Cell Int, 3, 17.
  16. 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.
  17. Pookot D, Li LC, Tabatabai ZL, et al (2006). The E-cadherin −160 c/a polymorphism and prostate cancer risk in white and black american Men. J Urol, 176, 793-6.
  18. Porter JI (2009). Is Art Modern? Kristeller’s ‘Modern System of the Arts’ Reconsidered. Br J Aesth, 49, 1-24.
  19. Qiu LX, Li RT, Zhang JB, et al (2008). The E-cadherin (CDH1) −160 C/A polymorphism and prostate cancer risk: a metaanalysis. Eur J Hum Genet, 17, 244-9.
  20. Ringwald M, Schuh R, Vestweber D, et al (1987). The structure of cell adhesion molecule uvomorulin. Insights into the molecular mechanism of $Ca^{2+}$-dependent cell adhesion. EMBO J, 6, 3647-53.
  21. Sarrio D, Moreno-Bueno G, Hardisson D, et al (2003). Epigenetic and genetic alterations of APC and CDH1 genes in lobular breast cancer: Relationships with abnormal E-cadherin and catenin expression and microsatellite instability. Int J Cancer, 106, 208-15.
  22. Shin Y. (2004). A functional polymorphism (-347 G->GA) in the E-cadherin gene is associated with colorectal cancer. Carcinogenesis, 25, 2173-6.
  23. Lichtenstein P, Holm NV, Verkasalo PK, et al (2000). Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med, 343, 78-85.
  24. Li Y, Liang J, Kang S, et al (2008). E-cadherin gene polymorphisms and haplotype associated with the occurrence of epithelial ovarian cancer in Chinese. Gynecol Oncol, 108, 409-14.
  25. Li Y, Tang Y, Zhou R, et al (2011). Genetic polymorphism in the 3’-untranslated region of the E-cadherin gene is associated with risk of different cancers. Mol Carcinog, 50, 857-62.
  26. Li YL, Tian Z, Zhang JB, Fu BY (2012). CDH1 promoter polymorphism and stomach cancer susceptibility. Mol Biol Rep, 39, 1283-6.
  27. Lindström S, Wiklund F, Jonsson BA, et al (2005). Comprehensive genetic evaluation of common E-cadherin sequence variants and prostate cancer risk: strong confirmation of functional promoter SNP. Human Genetics, 118, 339-47.
  28. 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.
  29. Mantel N, Haenszel W. (1959). Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst, 22, 719-48.
  30. Medina-Franco H, Ramos-De Ia Medina A, Vizcaino G, Medina-Franco JL. (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.
  31. 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.
  32. Kamoto T, Isogawa Y, Shhimizu Y, et al (2005). Association of a genetic polymorphism of the E-cadherin gene with prostate cancer in a Japanese population. Jpn J Clin Oncol, 35, 158-61.
  33. Jemal A, Bray F, Center MM, et al (2011). Global cancer statistics. CA Cancer J Clin, 61, 69-90.
  34. 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.
  35. Jonsson BA, Adami HO, Hagglund M, et al (2004). -160C/A polymorphism in the E-cadherin gene promoter and risk of hereditary, familial and sporadic prostate cancer. Int J Cancer, 109, 348-52.
  36. Kangelaris KN, Gruber SB (2007). Clinical implications of founder and recurrent CDH1 mutations in hereditary diffuse gastric cancer. JAMA, 297, 2410-1.
  37. Keirsebilck A, Van Hoorde L, Gao Y, et al (1998). Mechanisms of downregulation of transfected E-cadherin cDNA during formation of invasive tumors in syngeneic mice. Invasion Metastasis, 18, 44-56.
  38. Kiemeney LA, van Houwelingen KP, Bogaerts M, et al (2006). Polymorphisms in the E-cadherin (CDH1) gene promoter and the risk of bladder cancer. Eur J Cancer, 42, 3219-27.
  39. Lei H, Sjoberg-Margolin S, Salahshor S, et al (2002). CDH1 mutations are present in both ductal and lobular breast cancer, but promoter allelic variants show no detectable breast cancer risk. Int J Cancer, 98, 199-204.
  40. 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.
  41. Goto T, Nakano M, Ito S, et al (2007). Significance of an E-cadherin Gene Promoter Polymorphism for Risk and Disease Severity of Prostate Cancer in a Japanese Population. Urology, 70, 127-30.
  42. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88.
  43. Egger M, Davey Smith G, Schneider M, Minder C (1997). Bias in meta-analysis detected by a simple, graphical test. BMJ, 315, 629-34.
  44. Ghadimi BM, Behrens J, Hoffmann I, et al (1999). Immunohistological analysis of E-cadherin, alpha-, beta- and gamma-catenin expression in colorectal cancer: implications for cell adhesion and signaling. Eur J Cancer, 35, 60-5.
  45. Govatati S, Tangudu NK, Deenadayal M, et al (2011). Association of E-cadherin single nucleotide polymorphisms with the increased risk of endometriosis in Indian women. Mol Hum Reprod, 18, 280-7.
  46. Grünhage F, Jungck M, Lamberti C, et al (2007). Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes. Int J Colorectal Dis, 23, 147-54.
  47. Hajdinjak T, Toplak N (2004). E-cadherin polymorphism --160C/A and prostate cancer. Int J Cancer, 109, 480-1.
  48. Handoll HH (2006). Systematic reviews on rehabilitation interventions. Arch Phys Med Rehabil, 87, 875.
  49. Humar B, Toro F, Graziano F, et al (2002). Novel germlineCDH1 mutations in hereditary diffuse gastric cancer families. Human Mutation, 19, 518-25.
  50. Jacobs G, Hellmig S, Huse K, et al (2011). Polymorphisms in the 3’-untranslated region of the CDH1 gene are a risk factor for primary gastric diffuse large B-cell lymphoma. Haematologica, 96, 987-95.
  51. 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.
  52. Al-Moundhri MS (2010). Association of E-cadherin (CDH1) gene polymorphisms and gastric cancer risk. World J Gastroenterol, 16, 3432.
  53. Bonilla CT, Mason L, Long, et al (2006). E-cadherin polymorphisms and haplotypes influence risk for prostate cancer. Prostate, 66, 546-56.
  54. Borges BN, Santos ES, 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.
  55. Chien MH, Chou LS, Chung TT, et al (2012). Effects of E-cadherin (CDH1) gene promoter polymorphisms on the risk and clinicopathologic development of oral cancer. Head Neck, 34, 405-11.
  56. Chien MH, Yeh KT, Li YC, et al (2011). Effects of E-cadherin (CDH1) gene promoter polymorphisms on the risk and clinicopathological development of hepatocellular carcinoma. J Surg Oncol, 104, 299-304.
  57. 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.
  58. Corso G., Marrelli D, Pascale V, et al (2012). Frequency of CDH1 germline mutations in gastric carcinoma coming from high- and low-risk areas: metanalysis and systematic review of the literature. BMC Cancer, 12, 8.
  59. Cui Y, Xue H, Lin B, et al (2011). A meta-analysis of CDH1 C-160A genetic polymorphism and gastric cancer risk. DNA Cell Biol, 30, 937-45.
  60. de Lima JM, de Souza LG., da Silva ID, et al (2009). E-cadherin and metalloproteinase-1 and -7 polymorphisms in colorectal cancer. Int J Biol Markers, 24, 99-106.

Cited by

  1. Promoter methylation and polymorphism of E-cadherin gene may confer a risk to prostate cancer: a meta-analysis based on 22 studies vol.35, pp.10, 2014,
  2. Biomarkers for Evaluation of Prostate Cancer Prognosis vol.16, pp.7, 2015,
  3. Breast cancer risk in relation to TP53 codon 72 and CDH1 gene polymorphisms in the Bangladeshi women vol.37, pp.6, 2016,
  4. miR-199a-5p induces cell invasion by suppressing E-cadherin expression in cutaneous squamous cell carcinoma vol.12, pp.1, 2016,