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Combination of genetic variants in cyclin D1 and retinoblastoma genes predict clinical outcome in oral cancer patients

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Tumor Biology

Abstract

Oral cancer is a dreadful disease with a wide variation in geographical distribution. In order to identify some useful biomarkers for the disease prognosis, the present study assessed the influence of single nucleotide polymorphisms (SNPs) in cell cycle genes on survival in a well-annotated set of patients with oral squamous cell carcinoma (OSCC). The study examined 12 sequence variants or SNPs in selected cell cycle genes, with prognostic outcomes in 311 oral cancer patients. Our analysis showed that SNPs in cyclin D1:rs9344 and retinoblastoma:rs427686 genes showed a strong correlation with disease-free survival. In addition, the cumulative effect of these SNPs significantly and independently predicts the survival. Thus, the current study identified genotypes (SNP signature), which can be used as novel prognostic biomarkers to stratify patients based on disease-free survival and therefore maybe helpful in therapeutic decision-making.

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References

  1. Tanaka T, Tanaka M, Tanaka T. Oral carcinogenesis and oral cancer chemoprevention: a review. Pathol Res Int. 2011;2011:431246.

    Article  Google Scholar 

  2. Warnakulasuriya S. Global epidemiology of oral and oropharyngeal cancer. Oral Oncol. 2009;45(4–5):309–16.

    Article  PubMed  Google Scholar 

  3. Brinkman BM, Wong DT. Disease mechanism and biomarkers of oral squamous cell carcinoma. Curr Opin Oncol. 2006;18(3):228–33.

    Article  CAS  PubMed  Google Scholar 

  4. Nevins JR. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins. Science. 1992;258(5081):424–9.

    Article  CAS  PubMed  Google Scholar 

  5. Paternot S, Bockstaele L, Bisteau X, Kooken H, Coulonval K, Roger PP. Rb inactivation in cell cycle and cancer: the puzzle of highly regulated activating phosphorylation of CDK4 versus constitutively active CDK-activating kinase. Cell Cycle. 2010;9(4):689–99.

    Article  CAS  PubMed  Google Scholar 

  6. Hisanaga S, Endo R. Regulation and role of cyclin-dependent kinase activity in neuronal survival and death. J Neurochem. 2010;115(6):1309–21.

    Article  CAS  PubMed  Google Scholar 

  7. Todd R, Hinds PW, Munger K, Rustgi AK, Opitz OG, Suliman Y, et al. Cell cycle dysregulation in oral cancer. Crit Rev Oral Biol Med. 2002;13(1):51–61.

    Article  CAS  PubMed  Google Scholar 

  8. Regezi JA, Dekker NP, McMillan A, Ramirez-Amador V, Meneses-Garcia A, Ruiz-Godoy Rivera LM, et al. p53, p21, Rb, and MDM2 proteins in tongue carcinoma from patients <35 versus >75 years. Oral Oncol. 1999;35(4):379–83.

    Article  CAS  PubMed  Google Scholar 

  9. Pande P, Mathur M, Shukla NK, Ralhan R. pRb and p16 protein alterations in human oral tumorigenesis. Oral Oncol. 1998;34(5):396–403.

    Article  CAS  PubMed  Google Scholar 

  10. Bae DS, Cho SB, Kim YJ, Whang JD, Song SY, Park CS, et al. Aberrant expression of cyclin D1 is associated with poor prognosis in early stage cervical cancer of the uterus. Gynecol Oncol. 2001;81(3):341–7.

    Article  CAS  PubMed  Google Scholar 

  11. Barnes DM, Gillett CE. Cyclin D1 in breast cancer. Breast Cancer Res Treat. 1998;52(1–3):1–15.

    Article  CAS  PubMed  Google Scholar 

  12. Palmqvist R, Stenling R, Oberg A, Landberg G. Expression of cyclin D1 and retinoblastoma protein in colorectal cancer. Eur J Cancer. 1998;34(10):1575–81.

    Article  CAS  PubMed  Google Scholar 

  13. Callender T, el-Naggar AK, Lee MS, Frankenthaler R, Luna MA, Batsakis JG. PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. Cancer. 1994;74(1):152–8.

    Article  CAS  PubMed  Google Scholar 

  14. El-Naggar AK, Lai S, Clayman GL, Zhou JH, Tucker SA, Myers J, et al. Expression of p16, Rb, and cyclin D1 gene products in oral and laryngeal squamous carcinoma: biological and clinical implications. Hum Pathol. 1999;30(9):1013–8.

    Article  CAS  PubMed  Google Scholar 

  15. Mineta H, Miura K, Suzuki I, Takebayashi S, Amano H, Araki K, et al. Low p27 expression correlates with poor prognosis for patients with oral tongue squamous cell carcinoma. Cancer. 1999;85(5):1011–7.

    Article  CAS  PubMed  Google Scholar 

  16. Hopkins J, Cescon DW, Tse D, Bradbury P, Xu W, Ma C, et al. Genetic polymorphisms and head and neck cancer outcomes: a review. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2008;17(3):490–9.

    Article  CAS  Google Scholar 

  17. Wu X, Gu J, Grossman HB, Amos CI, Etzel C, Huang M, et al. Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet. 2006;78(3):464–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wu X, Gu J, Wu TT, Swisher SG, Liao Z, Correa AM, et al. Genetic variations in radiation and chemotherapy drug action pathways predict clinical outcomes in esophageal cancer. J Clin Oncol. 2006;24(23):3789–98.

    Article  CAS  PubMed  Google Scholar 

  19. Wagner KW, Ye Y, Lin J, Vaporciyan AA, Roth JA, Wu X. Genetic variations in epigenetic genes are predictors of recurrence in stage I or II non-small cell lung cancer patients. Clin Cancer Res. 2012;18(2):585–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Azad AK, Bairati I, Samson E, Cheng D, Mirshams M, Qiu X, et al. Validation of genetic sequence variants as prognostic factors in early-stage head and neck squamous cell cancer survival. Clin Cancer Res. 2012;18(1):196–206.

    Article  CAS  PubMed  Google Scholar 

  21. Quintela-Fandino M, Hitt R, Medina PP, Gamarra S, Manso L, Cortes-Funes H, et al. DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy. J Clin Oncol. 2006;24(26):4333–9.

    Article  CAS  PubMed  Google Scholar 

  22. Wang Z, Sturgis EM, Zhang F, Lei D, Liu Z, Xu L, et al. Genetic variants of p27 and p21 as predictors for risk of second primary malignancy in patients with index squamous cell carcinoma of head and neck. Mol Cancer. 2012;11:17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Murali A, Nalinakumari KR, Thomas S, Kannan S. Association of single nucleotide polymorphisms in cell cycle regulatory genes with oral cancer susceptibility. Br J Oral Maxillofac Surg. 2014;52(7):652–8.

    Article  PubMed  Google Scholar 

  24. Ye Y, Lippman SM, Lee JJ, Chen M, Frazier ML, Spitz MR, et al. Genetic variations in cell-cycle pathway and the risk of oral premalignant lesions. Cancer. 2008;113(9):2488–95.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Shubeita HE, Sambrook JF, McCormick AM. Molecular cloning and analysis of functional cDNA and genomic clones encoding bovine cellular retinoic acid-binding protein. Proc Natl Acad Sci U S A. 1987;84(16):5645–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Livak KJ. Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Gene Anal. 1999;14(5–6):143–9.

    Article  CAS  Google Scholar 

  27. Sole X, Guino E, Valls J, Iniesta R, Moreno V. SNPStats: a web tool for the analysis of association studies. Bioinformatics. 2006;22(15):1928–9.

    Article  CAS  PubMed  Google Scholar 

  28. Savas S, Liu G. Genetic variations as cancer prognostic markers: review and update. Hum Mutat. 2009;30(10):1369–77.

    Article  CAS  PubMed  Google Scholar 

  29. Rajaraman P, Wang SS, Rothman N, Brown MM, Black PM, Fine HA, et al. Polymorphisms in apoptosis and cell cycle control genes and risk of brain tumors in adults. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2007;16(8):1655–61.

    Article  CAS  Google Scholar 

  30. 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 

  31. Hung RJ, Boffetta P, Canzian F, Moullan N, Szeszenia-Dabrowska N, Zaridze D, et al. Sequence variants in cell cycle control pathway, X-ray exposure, and lung cancer risk: a multicenter case–control study in Central Europe. Cancer Res. 2006;66(16):8280–6.

    Article  CAS  PubMed  Google Scholar 

  32. Sathyan KM, Nalinakumari KR, Abraham T, Kannan S. CCND1 polymorphisms (A870G and C1722G) modulate its protein expression and survival in oral carcinoma. Oral Oncol. 2008;44(7):689–97.

    Article  CAS  PubMed  Google Scholar 

  33. 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.

    Article  CAS  PubMed  Google Scholar 

  34. Zhang W, Gordon M, Press OA, Rhodes K, Vallbohmer D, Yang DY, et al. Cyclin D1 and epidermal growth factor polymorphisms associated with survival in patients with advanced colorectal cancer treated with Cetuximab. Pharmacogenet Genomics. 2006;16(7):475–83.

    Article  CAS  PubMed  Google Scholar 

  35. Lesueur F, Song H, Ahmed S, Luccarini C, Jordan C, Luben R, et al. Single-nucleotide polymorphisms in the RB1 gene and association with breast cancer in the British population. Br J Cancer. 2006;94(12):1921–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Song H, Ramus SJ, Shadforth D, Quaye L, Kjaer SK, Dicioccio RA, et al. Common variants in RB1 gene and risk of invasive ovarian cancer. Cancer Res. 2006;66(20):10220–6.

    Article  CAS  PubMed  Google Scholar 

  37. Goode EL, Fridley BL, Vierkant RA, Cunningham JM, Phelan CM, Anderson S, et al. Candidate gene analysis using imputed genotypes: cell cycle single-nucleotide polymorphisms and ovarian cancer risk. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2009;18(3):935–44.

    Article  CAS  Google Scholar 

  38. Thakur N, Hussain S, Nasare V, Das BC, Basir SF, Bharadwaj M. Association analysis of p16 (CDKN2A) and RB1 polymorphisms with susceptibility to cervical cancer in Indian population. Mol Biol Rep. 2012;39(1):407–14.

    Article  CAS  PubMed  Google Scholar 

  39. Starinsky S, Figer A, Ben-Asher E, Geva R, Flex D, Fidder HH, et al. Genotype phenotype correlations in Israeli colorectal cancer patients. Int J Cancer. 2005;114(1):58–73.

    Article  CAS  PubMed  Google Scholar 

  40. Yu JC, Ding SL, Chang CH, Kuo SH, Chen ST, Hsu GC, et al. Genetic susceptibility to the development and progression of breast cancer associated with polymorphism of cell cycle and ubiquitin ligase genes. Carcinogenesis. 2009;30(9):1562–70.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The present study was financially supported by the FIST grant, no. 043/RDAUG/05/CSTE, of the Kerala State Committee for Science, Technology, and Environment, Government of Kerala, India. Abitha Murali was a recipient of Senior Research Fellowship of the Indian Council of Medical Research, Government of India.

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Authors and Affiliations

  1. Laboratory of Cell Cycle Regulation & Molecular Oncology, Division of Cancer Research, Regional Cancer Centre, Thiruvananthapuram, 695 011, Kerala, India

    Abitha Murali & S. Kannan

  2. Division of Surgical Oncology, Regional Cancer Centre, Thiruvananthapuram, 695 011, Kerala, India

    Bipin T. Varghese

  3. Division of Radiation Oncology, Regional Cancer Centre, Thiruvananthapuram, 695 011, Kerala, India

    R. Rejnish Kumar

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  1. Abitha Murali
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  4. S. Kannan
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Correspondence to S. Kannan.

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Murali, A., Varghese, B.T., Kumar, R.R. et al. Combination of genetic variants in cyclin D1 and retinoblastoma genes predict clinical outcome in oral cancer patients. Tumor Biol. 37, 3609–3617 (2016). https://doi.org/10.1007/s13277-015-4179-3

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  • DOI: https://doi.org/10.1007/s13277-015-4179-3

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