J Korean Surg Soc.  2012 Mar;82(3):156-164. 10.4174/jkss.2012.82.3.156.

Association of CTTN polymorphisms with the risk of colorectal cancer

Affiliations
  • 1Department of Surgery, Digestive Disease Research Institute and Institute of Medical Science, Wonkwang University College of Medicine, Iksan, Korea. rjk@wonkwang.ac.kr
  • 2Department of Pathology, Digestive Disease Research Institute and Institute of Medical Science, Wonkwang University College of Medicine, Iksan, Korea.

Abstract

PURPOSE
Various studies searching for biomarkers to predict tumor metastasis or prognosis in both esophageal squamous cell carcinoma (ESCC) and head and neck squamous cell carcinoma (HNSCC) are currently underway. However, few data have been reported on its association with colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) are the most common known form of human genetic variation and may contribute to an increased susceptibility to cancer including CRC. The present study aimed to investigate whether the polymorphisms in the CTTN gene are associated with susceptibility to CRC in the Korean population.
METHODS
A case-control study was performed to examine the relationship between the CTTN g.-9101C>T, g.-8748C>T, and g.72C>T polymorphisms and the risk of CRC. Polymerase chain reaction-restriction fragment length polymorphism analysis of g.-8748C>T, g.-9101C>T and Taqman analysis of g.72C>T were performed on blood samples from 218 patients with CRC and 533 control individuals. The g.-9101C>T, g.-8748C>T, and g.72C>T SNPs in CTTN and their haplotypes were analyzed.
RESULTS
The genotype and allele frequencies of g.-9101C>T, g.-8748C>T, and g.72C>T did not differ between the patient group and the control group. Further, the haplotype of CTTN g.-9101C>T, g.-8748C>T, and g.72C>T did not differ between patient group and the control group. However, the genotype and allele frequencies of CTTN g.-9101C>T were significantly increased in the lymph node positive CRC group compared to the control group.
CONCLUSION
The CTTN g.-9101C>T polymorphism may influence lymph node positive CRC.

Keyword

Genetic polymorphism; Human CTTN protein; Colorectal neoplasms

MeSH Terms

Biomarkers
Carcinoma, Squamous Cell
Case-Control Studies
Colorectal Neoplasms
Esophageal Neoplasms
Gene Frequency
Genetic Variation
Genotype
Haplotypes
Head
Humans
Lymph Nodes
Neck
Neoplasm Metastasis
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Prognosis
Carcinoma, Squamous Cell
Esophageal Neoplasms

Figure

  • Fig. 1 CTTN genotyping restriction fragment length polymorphism result. Restriction enzyme digestion of the polymerase chain reaction products for g.-9101C>T (630 bp) and g.-8748C>T (630 bp) yielded 2 fragments of 490 bp and 140 bp.


Reference

1. Salisbury BA, Pungliya M, Choi JY, Jiang R, Sun XJ, Stephens JC. SNP and haplotype variation in the human genome. Mutat Res. 2003. 526:53–61.
2. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010. 17:1471–1474.
3. Crawford NP, Colliver DW, Galandiuk S. Tumor markers and colorectal cancer: utility in management. J Surg Oncol. 2003. 84:239–248.
4. Morimoto Y, Ozaki T, Ouchida M, Umehara N, Ohata N, Yoshida A, et al. Single nucleotide polymorphism in fibroblast growth factor receptor 4 at codon 388 is associated with prognosis in high-grade soft tissue sarcoma. Cancer. 2003. 98:2245–2250.
5. van Rossum AG, Moolenaar WH, Schuuring E. Cortactin affects cell migration by regulating intercellular adhesion and cell spreading. Exp Cell Res. 2006. 312:1658–1670.
6. Greer RO Jr, Said S, Shroyer KR, Marileila VG, Weed SA. Overexpression of cyclin D1 and cortactin is primarily independent of gene amplification in salivary gland adenoid cystic carcinoma. Oral Oncol. 2007. 43:735–741.
7. Tsai WC, Jin JS, Chang WK, Chan DC, Yeh MK, Cherng SC, et al. Association of cortactin and fascin-1 expression in gastric adenocarcinoma: correlation with clinicopathological parameters. J Histochem Cytochem. 2007. 55:955–962.
8. Lee YY, Yu CP, Lin CK, Nieh S, Hsu KF, Chiang H, et al. Expression of survivin and cortactin in colorectal adenocarcinoma: association with clinicopathological parameters. Dis Markers. 2009. 26:9–18.
9. Spina C, Saccucci P, Bottini E, Gloria-Bottini F. ACP1 genetic polymorphism and colon cancer. Cancer Genet Cytogenet. 2008. 186:61–62.
10. Cao HX, Gao CM, Takezaki T, Wu JZ, Ding JH, Liu YT, et al. Genetic polymorphisms of methylenetetrahydrofolate reductase and susceptibility to colorectal cancer. Asian Pac J Cancer Prev. 2008. 9:203–208.
11. Jung H, Lee JI, Lee HH, Kim SH, Hur H, Jeon HM. Gastric cancer susceptibility according to methylenetetrahydrofolate reductase and thymidylate synthase gene polymorphism. J Korean Surg Soc. 2010. 79:27–34.
12. Stephens JC. Single-nucleotide polymorphisms, haplotypes, and their relevance to pharmacogenetics. Mol Diagn. 1999. 4:309–317.
13. Wu H, Parsons JT. Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex. J Cell Biol. 1993. 120:1417–1426.
14. Akervall JA, Jin Y, Wennerberg JP, Zätterström UK, Kjellén E, Mertens F, et al. Chromosomal abnormalities involving 11q13 are associated with poor prognosis in patients with squamous cell carcinoma of the head and neck. Cancer. 1995. 76:853–859.
15. Ormandy CJ, Musgrove EA, Hui R, Daly RJ, Sutherland RL. Cyclin D1, EMS1 and 11q13 amplification in breast cancer. Breast Cancer Res Treat. 2003. 78:323–335.
16. Takes RP, Baatenburg de Jong RJ, Schuuring E, Hermans J, Vis AA, Litvinov SV, et al. Markers for assessment of nodal metastasis in laryngeal carcinoma. Arch Otolaryngol Head Neck Surg. 1997. 123:412–419.
17. Freier K, Sticht C, Hofele C, Flechtenmacher C, Stange D, Puccio L, et al. Recurrent coamplification of cytoskeleton-associated genes EMS1 and SHANK2 with CCND1 in oral squamous cell carcinoma. Genes Chromosomes Cancer. 2006. 45:118–125.
18. Schuuring E. The involvement of the chromosome 11q13 region in human malignancies: cyclin D1 and EMS1 are two new candidate oncogenes: a review. Gene. 1995. 159:83–96.
19. Hui R, Campbell DH, Lee CS, McCaul K, Horsfall DJ, Musgrove EA, et al. EMS1 amplification can occur independently of CCND1 or INT-2 amplification at 11q13 and may identify different phenotypes in primary breast cancer. Oncogene. 1997. 15:1617–1623.
20. Timpson P, Wilson AS, Lehrbach GM, Sutherland RL, Musgrove EA, Daly RJ. Aberrant expression of cortactin in head and neck squamous cell carcinoma cells is associated with enhanced cell proliferation and resistance to the epidermal growth factor receptor inhibitor gefitinib. Cancer Res. 2007. 67:9304–9314.
21. Rothschild BL, Shim AH, Ammer AG, Kelley LC, Irby KB, Head JA, et al. Cortactin overexpression regulates actin-related protein 2/3 complex activity, motility, and invasion in carcinomas with chromosome 11q13 amplification. Cancer Res. 2006. 66:8017–8025.
22. van Rossum AG, van Bragt MP, Schuuring-Scholtes E, van der Ploeg JC, van Krieken JH, Kluin PM, et al. Transgenic mice with mammary gland targeted expression of human cortactin do not develop (pre-malignant) breast tumors: studies in MMTV-cortactin and MMTV-cortactin/-cyclin D1 bitransgenic mice. BMC Cancer. 2006. 6:58.
23. Weed SA, Du Y, Parsons JT. Translocation of cortactin to the cell periphery is mediated by the small GTPase Rac1. J Cell Sci. 1998. 111(Pt 16):2433–2443.
24. Mizutani K, Miki H, He H, Maruta H, Takenawa T. Essential role of neural Wiskott-Aldrich syndrome protein in podosome formation and degradation of extracellular matrix in src-transformed fibroblasts. Cancer Res. 2002. 62:669–674.
25. Patel AS, Schechter GL, Wasilenko WJ, Somers KD. Overexpression of EMS1/cortactin in NIH3T3 fibroblasts causes increased cell motility and invasion in vitro. Oncogene. 1998. 16:3227–3232.
26. Hirakawa H, Shibata K, Nakayama T. Localization of cortactin is associated with colorectal cancer development. Int J Oncol. 2009. 35:1271–1276.
27. Stephens JC, Schneider JA, Tanguay DA, Choi J, Acharya T, Stanley SE, et al. Haplotype variation and linkage disequilibrium in 313 human genes. Science. 2001. 293:489–493.
28. Ryk C, Kumar R, Thirumaran RK, Hou SM. Polymorphisms in the DNA repair genes XRCC1, APEX1, XRCC3 and NBS1, and the risk for lung cancer in never- and ever-smokers. Lung Cancer. 2006. 54:285–292.
29. Kupcinskas L, Wex T, Kupcinskas J, Leja M, Ivanauskas A, Jonaitis LV, et al. Interleukin-1B and interleukin-1 receptor antagonist gene polymorphisms are not associated with premalignant gastric conditions: a combined haplotype analysis. Eur J Gastroenterol Hepatol. 2010. 22:1189–1195.
30. Park KS, Kim SJ, Kim KH, Kim JC. Clinical characteristics of TIMP2, MMP2, and MMP9 gene polymorphisms in colorectal cancer. J Gastroenterol Hepatol. 2011. 26:391–397.
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