Skip to main content
SpringerLink
Log in

The significant association of CCND1 genotypes with colorectal cancer in Taiwan

  • Research Article
  • Published:
Tumor Biology

Abstract

Colorectal cancer, one million cases of diagnosis worldwide annually, is one of the most common malignant tumors and 20 % incidence caused by low penetrance susceptibility genes. Cyclin D1 (CCND1) regulating cell cycle transition may determine the susceptible individuals to genomic instability and carcinogenesis. The study aimed at examining the contribution of CCND1 genotypes to colorectal cancer risk in Taiwan. The genotypes of CCND1 A870G (rs9344) and G1722C (rs678653) were determined among 362 colorectal cancer patients and 362 age- and gender-matched cancer-free controls. Significant differences were observed between colorectal cancer and control groups in the distributions of genotypic (P = 9.71 × 10−4) and allelic (P = 0.0017) frequencies at CCND1 A870G. Additionally, individuals carried AG or GG genotype had 0.56- or 0.51-fold higher of odds ratios for developing colorectal cancer than the AA genotype (95 % confidence intervals = 0.40–0.78 and 0.32–0.81, respectively). Furthermore, G allele of CCND1 A870G performed a protective effects for nonsmokers and nonalcohol drinkers (P = 0.0012 and 0.0007, respectively) on colorectal cancer risk. These findings support the concept that the cell cycle regulation may play a role in colorectal cancer initiation and development and CCND1 A870G genotyping maybe a feasible technology for colorectal cancer early detection.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.

    Article  PubMed  Google Scholar 

  2. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin. 2011;61(2):69–90.

    Article  PubMed  Google Scholar 

  3. Nagini S. Carcinoma of the stomach: a review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol. 2012;4(7):156–69.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Jayasurya R, Sathyan KM, Lakshminarayanan K, Abraham T, Nalinakumari KR, Abraham EK, et al. Phenotypic alterations in Rb pathway have more prognostic influence than p53 pathway proteins in oral carcinoma. Mod Pathol. 2005;18(8):1056–66.

    Article  CAS  PubMed  Google Scholar 

  5. Butterworth AS, Higgins JP, Pharoah P. Relative and absolute risk of colorectal cancer for individuals with a family history: a meta-analysis. Eur J Cancer. 2006;42(2):216–27.

    Article  PubMed  Google Scholar 

  6. Houlston RS, Tomlinson IP. Polymorphisms and colorectal tumor risk. Gastroenterology. 2001;121(2):282–301.

    Article  CAS  PubMed  Google Scholar 

  7. Rasool S, Rasool V, Naqvi T, Ganai BA, Shah BA. Genetic unraveling of colorectal cancer. Tumour Biol. 2014;35(6):5067–82.

    Article  CAS  PubMed  Google Scholar 

  8. Hunter T, Pines J. Cyclins and cancer II: cyclin D and CDK inhibitors come of age. Cell. 1994;79(4):573–82.

    Article  CAS  PubMed  Google Scholar 

  9. Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer. 2001;1(3):222–31.

    Article  CAS  PubMed  Google Scholar 

  10. Ortega S, Malumbres M, Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta. 2002;1602(1):73–87.

    CAS  PubMed  Google Scholar 

  11. Cook SJ, Balmanno K, Garner A, Millar T, Taverner C, Todd D. Regulation of cell cycle re-entry by growth, survival and stress signalling pathways. Biochem Soc Trans. 2000;28(2):233–40.

    Article  CAS  PubMed  Google Scholar 

  12. Bova RJ, Quinn DI, Nankervis JS, Cole IE, Sheridan BF, Jensen MJ, et al. Cyclin D1 and p16INK4A expression predict reduced survival in carcinoma of the anterior tongue. Clin Cancer Res. 1999;5(10):2810–9.

    CAS  PubMed  Google Scholar 

  13. Michalides R, van Veelen N, Hart A, Loftus B, Wientjens E, Balm A. Overexpression of cyclin D1 correlates with recurrence in a group of forty-seven operable squamous cell carcinomas of the head and neck. Cancer Res. 1995;55(5):975–8.

    CAS  PubMed  Google Scholar 

  14. Wu Y, Fu H, Zhang H, Huang H, Chen M, Zhang L, et al. Cyclin D1 (CCND1) G870A polymorphisms and cervical cancer susceptibility: a meta-analysis based on ten case–control studies. Tumour Biol. 2014;35(7):6913–8.

    Article  CAS  PubMed  Google Scholar 

  15. Vizkeleti L, Ecsedi S, Rakosy Z, Orosz A, Lazar V, Emri G, et al. The role of CCND1 alterations during the progression of cutaneous malignant melanoma. Tumour Biol. 2012;33(6):2189–99.

    Article  CAS  PubMed  Google Scholar 

  16. Tsai MH, Tsai CW, Tsou YA, Hua CH, Hsu CF, Bau DT. Significant association of cyclin D1 single nucleotide polymorphisms with oral cancer in Taiwan. Anticancer Res. 2011;31(1):227–31.

    CAS  PubMed  Google Scholar 

  17. Shih LC, Tsai CW, Tsai MH, Tsou YA, Chang WS, Li FJ, et al. Association of cyclin D1 genotypes with nasopharyngeal carcinoma risk. Anticancer Res. 2012;32(3):1093–8.

    CAS  PubMed  Google Scholar 

  18. Hussain SMY, Thakur N, Salam I, Singh N, Mir MM, et al. Association of cyclin D1 gene polymorphisms with risk of esophageal squamous cell carcinoma in Kashmir Valley: a high risk area. Mol Carcinog. 2011;50(7):487–98.

    Article  CAS  PubMed  Google Scholar 

  19. Hsia TC, Liu CJ, Lin CH, Chang WS, Chu CC, Hang LW, et al. Interaction of CCND1 genotype and smoking habit in Taiwan lung cancer patients. Anticancer Res. 2011;31(10):3601–5.

    CAS  PubMed  Google Scholar 

  20. Yu CC, Lin VC, Huang CY, Liu CC, Wang JS, Wu TT, et al. Prognostic significance of cyclin D1 polymorphisms on prostate-specific antigen recurrence after radical prostatectomy. Ann Surg Oncol. 2013;20 Suppl 3:S492–9.

    Article  PubMed  Google Scholar 

  21. Liu B, Zhang Y, Jin M, Ni Q, Liang X, Ma X, et al. Association of selected polymorphisms of CCND1, p21, and caspase8 with colorectal cancer risk. Mol Carcinog. 2010;49(1):75–84.

    CAS  PubMed  Google Scholar 

  22. Forones NM, de Lima JM, de Souza LG, da Silva ID. Cyclin D1 A870G polymorphism in Brazilian colorectal cancer patients. J Gastrointest Cancer. 2008;39(1–4):118–23.

    Article  CAS  PubMed  Google Scholar 

  23. Grunhage F, Jungck M, Lamberti C, Berg C, Becker U, Schulte-Witte H, et al. Association of familial colorectal cancer with variants in the E-cadherin (CDH1) and cyclin D1 (CCND1) genes. Int J Color Dis. 2008;23(2):147–54.

    Article  Google Scholar 

  24. Talseth BA, Ashton KA, Meldrum C, Suchy J, Kurzawski G, Lubinski J, et al. Aurora-A and Cyclin D1 polymorphisms and the age of onset of colorectal cancer in hereditary nonpolyposis colorectal cancer. Int J Cancer. 2008;122(6):1273–7.

    Article  CAS  PubMed  Google Scholar 

  25. Tan XL, Nieters A, Kropp S, Hoffmeister M, Brenner H, Chang-Claude J. 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. 2008;122(11):2573–80.

    Article  CAS  PubMed  Google Scholar 

  26. Jiang J, Wang J, Suzuki S, Gajalakshmi V, Kuriki K, Zhao Y, et al. Elevated risk of colorectal cancer associated with the AA genotype of the cyclin D1 A870G polymorphism in an Indian population. J Cancer Res Clin Oncol. 2006;132(3):193–9.

    Article  CAS  PubMed  Google Scholar 

  27. Kruger S, Engel C, Bier A, Mangold E, Pagenstecher C, Doeberitz M, et al. Absence of association between cyclin D1 (CCND1) G870A polymorphism and age of onset in hereditary nonpolyposis colorectal cancer. Cancer Lett. 2006;236(2):191–7.

    Article  PubMed  Google Scholar 

  28. Probst-Hensch NM, Sun CL, Van Den Berg D, Ceschi M, Koh WP, Yu MC. The effect of the cyclin D1 (CCND1) A870G polymorphism on colorectal cancer risk is modified by glutathione-S-transferase polymorphisms and isothiocyanate intake in the Singapore Chinese health study. Carcinogenesis. 2006;27(12):2475–82.

    Article  CAS  PubMed  Google Scholar 

  29. Schernhammer ES, Tranah GJ, Giovannucci E, Chan AT, Ma J, Colditz GA, et al. Cyclin D1 A870G polymorphism and the risk of colorectal cancer and adenoma. Br J Cancer. 2006;94(6):928–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Hong Y, Eu KW, Seow-Choen F, Fook-Chong S, Cheah PY. GG genotype of cyclin D1 G870A polymorphism is associated with increased risk and advanced colorectal cancer in patients in Singapore. Eur J Cancer. 2005;41(7):1037–44.

    Article  CAS  PubMed  Google Scholar 

  31. Grieu F, Malaney S, Ward R, Joseph D, Iacopetta B. Lack of association between CCND1 G870A polymorphism and the risk of breast and colorectal cancers. Anticancer Res. 2003;23(5b):4257–9.

    CAS  PubMed  Google Scholar 

  32. Le Marchand L, Seifried A, Lum-Jones A, Donlon T, Wilkens LR. Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer. JAMA. 2003;290(21):2843–8.

    Article  PubMed  Google Scholar 

  33. Lewis RC, Bostick RM, Xie D, Deng Z, Wargovich MJ, Fina MF, et al. Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas. Cancer Res. 2003;63(23):8549–53.

    CAS  PubMed  Google Scholar 

  34. Porter TR, Richards FM, Houlston RS, Evans DG, Jankowski JA, Macdonald F, et al. Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. Oncogene. 2002;21(12):1928–33.

    Article  CAS  PubMed  Google Scholar 

  35. Kong S, Wei Q, Amos CI, Lynch PM, Levin B, Zong J, et al. Cyclin D1 polymorphism and increased risk of colorectal cancer at young age. J Natl Cancer Inst. 2001;93(14):1106–8.

    Article  CAS  PubMed  Google Scholar 

  36. McKay JA, Douglas JJ, Ross VG, Curran S, Murray GI, Cassidy J, et al. Cyclin D1 protein expression and gene polymorphism in colorectal cancer. Aberdeen colorectal initiative. Int J Cancer. 2000;88(1):77–81.

    Article  CAS  PubMed  Google Scholar 

  37. Yang MD, Hsu YM, Kuo YS, Chen HS, Chang CL, Wu CN, et al. Significant association of Ku80 single nucleotide polymorphisms with colorectal cancer susceptibility in Central Taiwan. Anticancer Res. 2009;29(6):2239–42.

    CAS  PubMed  Google Scholar 

  38. Bau DT, Yang MD, Tsou YA, Lin SS, Wu CN, Hsieh HH, et al. Colorectal cancer and genetic polymorphism of DNA double-strand break repair gene XRCC4 in Taiwan. Anticancer Res. 2010;30(7):2727–30.

    CAS  PubMed  Google Scholar 

  39. Yang MD, Tsai RY, Liu CS, Chang CH, Wang HC, Tsou YA, et al. Association of Caveolin-1 polymorphisms with colorectal cancer susceptibility in Taiwan. World J Gastrointest Oncol. 2010;2(8):326–31.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Donnellan R, Chetty R. Cyclin D1 and human neoplasia. Mol Pathol. 1998;51(1):1–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bala S, Peltomaki P. CYCLIN D1 as a genetic modifier in hereditary nonpolyposis colorectal cancer. Cancer Res. 2001;61(16):6042–5.

    CAS  PubMed  Google Scholar 

  42. Yang J, Zhang G, Chen J. CCND1 G870A polymorphism is associated with increased risk of colorectal cancer, especially for sporadic colorectal cancer and in Caucasians: a meta-analysis. Clin Res Hepatol Gastroenterol. 2012;36(2):169–77.

    Article  CAS  PubMed  Google Scholar 

  43. Chen B, Cao L, Yang P, Zhou Y, Wu XT. Cyclin D1 (CCND1) G870A gene polymorphism is an ethnicity-dependent risk factor for digestive tract cancers: a meta-analysis comprising 20,271 subjects. Cancer Epidemiol. 2012;36(2):106–15.

    Article  CAS  PubMed  Google Scholar 

  44. Fan YZ, Fu JY, Zhao ZM, Chen CQ. Inhibitory effect of norcantharidin on the growth of human gallbladder carcinoma GBC-SD cells in vitro. Hepatobiliary Pancreat Dis Int. 2007;6(1):72–80.

    CAS  PubMed  Google Scholar 

  45. Sobti RC, Kaur P, Kaur S, Singh J, Janmeja AK, Jindal SK, et al. Effects of cyclin D1 (CCND1) polymorphism on susceptibility to lung cancer in a North Indian population. Cancer Genet Cytogenet. 2006;170(2):108–14.

    Article  CAS  PubMed  Google Scholar 

  46. Lu C, Dong J, Ma H, Jin G, Hu Z, Peng Y, et al. CCND1 G870A polymorphism contributes to breast cancer susceptibility: a meta-analysis. Breast Cancer Res Treat. 2009;116(3):571–5.

    Article  CAS  PubMed  Google Scholar 

  47. Li Z, Jiao X, Wang C, Shirley LA, Elsaleh H, Dahl O, et al. Alternative cyclin D1 splice forms differentially regulate the DNA damage response. Cancer Res. 2010;70(21):8802–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by research grants from Taichung Armed Forces General Hospital (103A04 and 103A24) and in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW103-TDU-B-212-113002). The assistance from Mei-Due Yang and Tsai-Ping Ho in sample and questionnaire collection, and genotyping work from Hong-XueJi, Chieh-Lun Hsiao, Tzu-Chia Wang, Yun-Ru Syu, Lin-Lin Hou, and Chia-En Miao were highly appreciated by the authors.

Conflicts of interest

None

Author information

Author notes

    Authors and Affiliations

    1. Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China

      Chung-Yu Huang & Hao-Ai Shui

    2. Terry Fox Cancer Research Laboratory, China Medical University Hospital, 2 Yuh-Der Road, Taichung, 404, Taiwan, Republic of China

      Chia-Wen Tsai, Chin-Mu Hsu, Wen-Shin Chang & Da-Tian Bau

    3. Taichung Armed-Forces General Hospital, Taichung, Taiwan, Republic of China

      Chung-Yu Huang

    4. Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, Republic of China

      Wen-Shin Chang & Da-Tian Bau

    5. Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, Republic of China

      Da-Tian Bau

    Authors
    1. Chung-Yu Huang
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Chia-Wen Tsai
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Chin-Mu Hsu
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Wen-Shin Chang
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Hao-Ai Shui
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Da-Tian Bau
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding authors

    Correspondence to Hao-Ai Shui or Da-Tian Bau.

    Additional information

    Chung-Yu Huang and Chia-Wen Tsai contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Huang, CY., Tsai, CW., Hsu, CM. et al. The significant association of CCND1 genotypes with colorectal cancer in Taiwan. Tumor Biol. 36, 6533–6540 (2015). https://doi.org/10.1007/s13277-015-3347-9

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13277-015-3347-9

    Keywords

    Search

    Navigation