No association between the polymorphisms in CDX2 coding regions and colorectal cancer in Chinese

  • Xiaoping Xia
  • Enping Xu
  • Sheng Quan
  • Qiong Huang
  • Maode Lai


CDX2 has been shown to play an important role in the pathogenesis of colorectal cancer. The aim of this study was to investigate whether genetic variants in CDX2 contributed to the development and progression of colorectal cancer in a Chinese population. We detected the polymorphisms in the CDX2 coding regions in 126 patients with colorectal cancer and matched tumor-free subjects by PCR-based DHPLC. The correlation between the genotypes and clinicopathological parameters among colorectal cancer cases was also investigated. Three SNPs were identified in the coding region of the CDX2 gene. Neither the genotype frequencies nor allele frequencies of CDX2 polymorphisms showed significant difference from those in healthy controls. There were also no significant association between genotypes and clinicopathological features. When we examined the linkage disequilibrium between three SNPs using expectation-maximization algorithm, we found that there is strong linkage disequilibrium among these SNPs, but no significant difference was found in haplotypes distribution. Our present data suggest that the CDX2 polymorphisms may not be used as a useful marker to predicate susceptibility of colorectal cancer in Chinese.


CDX2 Colorectal cancer Polymorphism 



This work was supported by grants from the National Natural Science Foundation of China (NSFC: 30801326) and Natural Science Foundation of Zhejiang Province (Y206084) and Research Foundation of Education Bureau of Zhejiang Province (20061412).


  1. 1.
    Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767. doi: 10.1016/0092-8674(90)90186-I CrossRefPubMedGoogle Scholar
  2. 2.
    Vogelstein B, Kinzler KW (1993) The multistep nature of cancer. Trends Genet 9:138–141. doi: 10.1016/0168-9525(93)90209-Z CrossRefPubMedGoogle Scholar
  3. 3.
    Duluc I, Lorentz O, Fritsch C et al (1997) Changing intestinal connective tissue interactions alters homeobox gene expression in epithelial cells. J Cell Sci 110(Pt 11):1317–1324PubMedGoogle Scholar
  4. 4.
    Lorentz O, Duluc I, Arcangelis AD et al (1997) Key role of the Cdx2 homeobox gene in extracellular matrix-mediated intestinal cell differentiation. J Cell Biol 139:1553–1565. doi: 10.1083/jcb.139.6.1553 CrossRefPubMedGoogle Scholar
  5. 5.
    Chawengsaksophak K, James R, Hammond VE et al (1997) Homeosis and intestinal tumours in Cdx2 mutant mice. Nature 386:84–87. doi: 10.1038/386084a0 CrossRefPubMedGoogle Scholar
  6. 6.
    Ee HC, Erler T, Bhathal PS et al (1995) Cdx-2 homeodomain protein expression in human and rat colorectal adenoma and carcinoma. Am J Pathol 147:586–592PubMedGoogle Scholar
  7. 7.
    Hinoi T, Tani M, Lucas PC et al (2001) Loss of CDX2 expression and microsatellite instability are prominent features of large cell minimally differentiated carcinomas of the colon. Am J Pathol 159:2239–2248PubMedGoogle Scholar
  8. 8.
    Sowden J, Leigh S, Talbot I et al (1993) Expression from the proximal promoter of the carbonic anhydrase 1 gene as a marker for differentiation in colon epithelia. Differentiation 53:67–74. doi: 10.1111/j.1432-0436.1993.tb00647.x CrossRefPubMedGoogle Scholar
  9. 9.
    Sivagnanasundaram S, Islam I, Talbot I et al (2001) The homeobox gene CDX2 in colorectal carcinoma: a genetic analysis. Br J Cancer 84:218–225. doi: 10.1054/bjoc.2000.1544 CrossRefPubMedGoogle Scholar
  10. 10.
    Rozek LS, Lipkin SM, Fearon ER et al (2005) CDX2 polymorphisms, RNA expression, and risk of colorectal cancer. Cancer Res 65:5488–5492. doi: 10.1158/0008-5472.CAN-04-3645 CrossRefPubMedGoogle Scholar
  11. 11.
    Xu E, Lai M, Lv B et al (2004) A single nucleotide polymorphism in the matrix metalloproteinase-2 promoter is associated with colorectal cancer. Biochem Biophys Res Commun 324:999–1003. doi: 10.1016/j.bbrc.2004.09.150 CrossRefPubMedGoogle Scholar
  12. 12.
    Gross E, Arnold N, Goette J et al (1999) A comparison of BRCA1 mutation analysis by direct sequencing, SSCP and DHPLC. Hum Genet 105:72–78. doi: 10.1007/s004390051066 CrossRefPubMedGoogle Scholar
  13. 13.
    Taillon-Miller P, Bauer-Sardina I, Saccone NL et al (2000) Juxtaposed regions of extensive and minimal linkage disequilibrium in human Xq25 and Xq28. Nat Genet 25:324–328. doi: 10.1038/77100 CrossRefPubMedGoogle Scholar
  14. 14.
    Zhao JH, Curtis D, Sham PC (2000) Model-free analysis and permutation tests for allelic associations. Hum Hered 50:133–139. doi: 10.1159/000022901 CrossRefPubMedGoogle Scholar
  15. 15.
    Lin YM, Kato T, Satoh S et al (2000) Identification of novel polymorphisms in the AXIN1++ and CDX-2 genes. J Hum Genet 45:254–256. doi: 10.1007/s100380070036 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Xiaoping Xia
    • 1
  • Enping Xu
    • 2
  • Sheng Quan
    • 3
  • Qiong Huang
    • 2
  • Maode Lai
    • 2
  1. 1.Clinical Laboratory of Sir Run Run Shaw Hospital, Affiliated with School of MedicineZhejiang UniversityHangzhouChina
  2. 2.Department of Pathology and Pathophysiology, Center for Environmental Genomics, School of MedicineZhejiang UniversityHangzhouChina
  3. 3.Zhejiang University City CollegeHangzhouChina

Personalised recommendations