Evaluation of Relative Frequency of Single Nucleotide Polymorphism G870A (rs9344) in CyclinD1 Gene in Colorectal Cancer Patients and Healthy Subjects of Isfahan Province, Iran

Document Type : Original Article (s)

Authors

1 MSc Student, Department of Genetic, School of Sciences, Shahrekord University, Shahrekord, Iran

2 Professor, Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

3 Assistant Professor, Department of Genetics, School of Sciences, Shahrekord University, Shahrekord, Iran

Abstract

Background: Colorectal cancer (CRC) is one of the most common cancers in the world. High activity of CyclinD1 gene has been seen in the progress of this cancer. A common polymorphism (G870A) in exon 4 of CyclinD1 produces a variant transcript with longer half-life and may cause uncontrollable cellular growth thus contributing to cancer development. This study was performed to evaluate the frequency of CCND1 G870A polymorphism between CRC cases and controls.Methods: DNA samples from peripheral blood leukocytes of 50 patients with sporadic colorectal cancer and 50 healthy subjects were extracted. CCND1 G870A polymorphism was genotyped by polymerase chain reaction -restriction fragment length polymorphism (PCR-RFLP) in healthy subjects and patients. Statistical analysis was performed by chi-squared test via SPSS software.Findings: Relationship between CCND1 G870A polymorphism in allele frequencies between cases and controls were not observed (P = 0.204). While the frequency of AA genotype was significantly higher in patients (P = 0.040, 95% CI = 1.13-5.54, OR = 2.25).Conclusion: According to the significant association observed between certain genotypes of this locus (AA) with colorectal cancer, it can be used in the future as a good prognostic marker in CRC screening programs.

Keywords


  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin 2015; 65(1): 5-29.
  2. Mahmodlou R, Mohammadi P, Sepehrvand N. Colorectal cancer in northwestern iran. ISRN Gastroenterol 2012; 2012: 968560.
  3. Li D, Conti DV. Detecting gene-environment interactions using a combined case-only and case-control approach. Am J Epidemiol 2009; 169(4): 497-504.
  4. Kato JY, Yoneda-Kato N. New twist in the regulation of cyclin D1. Biomol Concepts 2010; 1(5-6): 403-9.
  5. Yang Y, Wang F, Shi C, Zou Y, Qin H, Ma Y. Cyclin D1 G870A polymorphism contributes to colorectal cancer susceptibility: evidence from a systematic review of 22 case-control studies. PLoS One 2012; 7(5): e36813.
  6. Loh SF, Cooper C, Selinger CI, Barnes EH, Chan C, Carmalt H, et al. Cell cycle marker expression in benign and malignant intraductal papillary lesions of the breast. J Clin Pathol 2015; 68(3): 187-91.
  7. Pabalan N, Bapat B, Sung L, Jarjanazi H, Francisco-Pabalan O, Ozcelik H. Cyclin D1 Pro241Pro (CCND1-G870A) polymorphism is associated with increased cancer risk in human populations: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2008; 17(10): 2773-81.
  8. Knudsen KE, Diehl JA, Haiman CA, Knudsen ES. Cyclin D1: polymorphism, aberrant splicing and cancer risk. Oncogene 2006; 25(11): 1620-8.
  9. Solomon DA, Wang Y, Fox SR, Lambeck TC, Giesting S, Lan Z, et al. Cyclin D1 splice variants. Differential effects on localization, RB phosphorylation, and cellular transformation. J Biol Chem 2003; 278(32): 30339-47.
  10. Gylfe AE, Katainen R, Kondelin J, Tanskanen T, Cajuso T, Hanninen U, et al. Eleven candidate susceptibility genes for common familial colorectal cancer. PLoS Genet 2013; 9(10): e1003876.
  11. Abuli A, Bessa X, Gonzalez JR, Ruiz-Ponte C, Caceres A, Munoz J, et al. Susceptibility genetic variants associated with colorectal cancer risk correlate with cancer phenotype. Gastroenterology 2010; 139(3): 788-96, 796.
  12. Le ML, 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.
  13. Lu F, Gladden AB, Diehl JA. An alternatively spliced cyclin D1 isoform, cyclin D1b, is a nuclear oncogene. Cancer Res 2003; 63(21): 7056-61.
  14. Li Y, Zhang S, Geng JX, Yu Y. Effects of the cyclin D1 polymorphism on lung cancer risk--a meta-analysis. Asian Pac J Cancer Prev 2012; 13(5): 2325-8.
  15. Rydzanicz M, Golusinski P, Mielcarek-Kuchta D, Golusinski W, Szyfter K. Cyclin D1 gene (CCND1) polymorphism and the risk of squamous cell carcinoma of the larynx. Eur Arch Otorhinolaryngol 2006; 263(1): 43-8.
  16. Yu CP, Yu JC, Sun CA, Tzao C, Ho JY, Yen AM. Tumor susceptibility and prognosis of breast cancer associated with the G870A polymorphism of CCND1. Breast Cancer Res Treat 2008; 107(1): 95-102.
  17. 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.
  18. 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.
  19. 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.
  20. Yaylim-Eraltan I, Arikan S, Yildiz Y, Cacina C, Ergen HA, Tuna G, et al. The influence of cyclin D1 A870G polymorphism on colorectal cancer risk and prognosis in a Turkish population. Anticancer Res 2010; 30(7): 2875-80.
  21. 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.
  22. 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.
  23. Sameer AS, Parray FQ, Dar MA, Nissar S, Banday MZ, Rasool S, et al. Cyclin D1 G870A polymorphism and risk of colorectal cancer: a case control study. Mol Med Rep 2013; 7(3): 811-5.
  24. Zhang LQ, Wang J, Shang JQ, Bai JL, Liu FY, Guan X, et al. Cyclin D1 G870A polymorphism and colorectal cancer susceptibility: a meta-analysis of 20 populations. Int J Colorectal Dis 2011; 26(10): 1249-55.
  25. 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.
  26. Ruder EH, Laiyemo AO, Graubard BI, Hollenbeck AR, Schatzkin A, Cross AJ. Non-steroidal anti-inflammatory drugs and colorectal cancer risk in a large, prospective cohort. Am J Gastroenterol 2011; 106(7): 1340-50.
  27. Vainio H, Morgan G, Kleihues P. An international evaluation of the cancer-preventive potential of nonsteroidal anti-inflammatory drugs. Cancer Epidemiol Biomarkers Prev 1997; 6(9): 749-53.