Tumor Biology

, Volume 36, Issue 8, pp 6533–6540 | Cite as

The significant association of CCND1 genotypes with colorectal cancer in Taiwan

Research Article

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.

Keywords

Colorectal cancer Cyclin D1 Drinking Genotype Polymorphism Smoking 

Notes

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

References

  1. 1.
    Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin. 2010;60(5):277–300.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.CrossRefPubMedGoogle Scholar
  6. 6.
    Houlston RS, Tomlinson IP. Polymorphisms and colorectal tumor risk. Gastroenterology. 2001;121(2):282–301.CrossRefPubMedGoogle Scholar
  7. 7.
    Rasool S, Rasool V, Naqvi T, Ganai BA, Shah BA. Genetic unraveling of colorectal cancer. Tumour Biol. 2014;35(6):5067–82.CrossRefPubMedGoogle Scholar
  8. 8.
    Hunter T, Pines J. Cyclins and cancer II: cyclin D and CDK inhibitors come of age. Cell. 1994;79(4):573–82.CrossRefPubMedGoogle Scholar
  9. 9.
    Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer. 2001;1(3):222–31.CrossRefPubMedGoogle Scholar
  10. 10.
    Ortega S, Malumbres M, Barbacid M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim Biophys Acta. 2002;1602(1):73–87.PubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.PubMedGoogle Scholar
  13. 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.PubMedGoogle Scholar
  14. 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.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 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.PubMedGoogle Scholar
  17. 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.PubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.PubMedGoogle Scholar
  20. 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.CrossRefPubMedGoogle Scholar
  21. 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.PubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 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.CrossRefGoogle Scholar
  24. 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.CrossRefPubMedGoogle Scholar
  25. 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.CrossRefPubMedGoogle Scholar
  26. 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.CrossRefPubMedGoogle Scholar
  27. 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.CrossRefPubMedGoogle Scholar
  28. 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.CrossRefPubMedGoogle Scholar
  29. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 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.CrossRefPubMedGoogle Scholar
  31. 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.PubMedGoogle Scholar
  32. 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.CrossRefPubMedGoogle Scholar
  33. 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.PubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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.CrossRefPubMedGoogle Scholar
  36. 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.CrossRefPubMedGoogle Scholar
  37. 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.PubMedGoogle Scholar
  38. 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.PubMedGoogle Scholar
  39. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Donnellan R, Chetty R. Cyclin D1 and human neoplasia. Mol Pathol. 1998;51(1):1–7.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Bala S, Peltomaki P. CYCLIN D1 as a genetic modifier in hereditary nonpolyposis colorectal cancer. Cancer Res. 2001;61(16):6042–5.PubMedGoogle Scholar
  42. 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.CrossRefPubMedGoogle Scholar
  43. 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.CrossRefPubMedGoogle Scholar
  44. 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.PubMedGoogle Scholar
  45. 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.CrossRefPubMedGoogle Scholar
  46. 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.CrossRefPubMedGoogle Scholar
  47. 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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Graduate Institute of Medical SciencesNational Defense Medical CenterTaipeiRepublic of China
  2. 2.Terry Fox Cancer Research LaboratoryChina Medical University HospitalTaichungRepublic of China
  3. 3.Taichung Armed-Forces General HospitalTaichungRepublic of China
  4. 4.Graduate Institute of Clinical Medical ScienceChina Medical UniversityTaichungRepublic of China
  5. 5.Department of Bioinformatics and Medical EngineeringAsia UniversityTaichungRepublic of China

Personalised recommendations