Cyclin D1 and p21 gene variants and oral squamous cell carcinoma risk and prognosis

Authors

  • Saša Jović Clinic for Maxillofacial Surgery, Military Medical Academy, Belgrade, Serbia
  • Katarina Zeljić Faculty of Biology, University of Belgrade, Belgrade, Serbia
  • Nemanja Ivković Institute of Medical Research, Military Medical Academy, Belgrade, Serbia
  • Debora Štefik Institute of Medical Research, Military Medical Academy, Belgrade, Serbia
  • Ružica Kozomara 1. Clinic for Maxillofacial Surgery, Military Medical Academy, Belgrade, Serbia; 2. Medical Faculty of Military Medical Academy, University of Defense, Belgrade, Serbia
  • Srboljub Stošić 1. Clinic for Maxillofacial Surgery, Military Medical Academy, Belgrade, Serbia; 2. Medical Faculty of Military Medical Academy, University of Defense, Belgrade, Serbia
  • Gordana Šupić 1. Medical Faculty of Military Medical Academy, University of Defense, Belgrade, Serbia; 2. Institute of Medical Research, Military Medical Academy, Belgrade, Serbia

DOI:

https://doi.org/10.2298/ABS210813037J

Keywords:

p21, cyclin D1, gene polymorphism, oral squamous cell carcinoma

Abstract

Paper description:

  • p21 and cyclin D1, encoded by the CDKN1A and the CCND1 genes, respectively, are important regulators of cell cycle progression and could be associated with oral cancer.
  • Gene variants within the CDKN1A (rs1801270, rs1059234) and CCND1 (rs9344) were genotyped by real-time PCR in a group of 104 oral cancer patients and 107 healthy controls.
  • CCND1 polymorphism rs9344 was significantly associated with increased oral cancer risk but not with its prognosis.
  • Variant rs9344 in the CCND1 gene could be considered as a potential marker for oral cancer susceptibility and might be potentially useful for future cancer risk assessment.

Abstract: Cyclin-dependent kinase inhibitor p21 (encoded by the CDKN1A gene) and cyclin D1 (encoded by the CCND1 gene) are important regulators of cell cycle progression and could have important effects in the complex process of neoplastic transformation. The current study aimed to investigate variants in CDKN1A (rs1801270, rs1059234) and CCND1 (rs9344) genes as potential risk and prognostic factors in oral squamous cell carcinoma (OSCC) patients. The study included 104 OSCC patients and 107 healthy individuals without a history of cancer. Genotypes were assessed by real-time PCR and TaqMan SNP genotyping. Significant differences in genotype distribution between OSCC cases and the control group were observed for the CCND1 rs9344 variant (p=0.017). According to the odds ratio (OR), adjusted for age and sex, the rs9344 heterozygous GA and homozygous mutated AA genotypes were associated with an increased OSCC susceptibility (OR=2.295, p=0.007; OR=2.029, p=0.037, respectively). Variants rs1801270 and rs105923 in CDKN1A were not associated with OSCC risk. There were no differences in overall survival among OSCC patients stratified by genotypes of the analyzed variants in CDKN1A and CCND1. Variant rs9344 in the CCND1 gene might be considered as a potential molecular risk factor for OSCC susceptibility but not for disease prognosis.

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References

Montero PH, Patel SG. Cancer of the oral cavity. Surg Oncol Clin N Am. 2015;24(3):491-508.

https://doi.org/10.1016/j.soc.2015.03.006

Markopoulos AK. Current Aspects on Oral Squamous Cell Carcinoma. Open Dent J. 2012;6:126-30.

https://doi.org/10.2174/1874210601206010126

Friedlander PL. Genomic Instability in Head and Neck Cancer Patients. Head Neck. 2001;23(8):683-91.

https://doi.org/10.1002/hed.1096

Poon RY, Jiang W, Toyoshima H, Hunter T. Cyclin-Dependent Kinases Are Inactivated by a Combination of P21 and Thr-14/Tyr-15 Phosphorylation After UV-Induced DNA Damage. J Biol Chem. 1996;271(22):13283-91.

https://doi.org/10.1074/jbc.271.22.13283

Matsuoka S, Edwards MC, Bai C, Parker S, Zhang P, Baldini A, Harper JW, Elledge SJ. p57KIP2, a Structurally Distinct Member of the P21cip1 Cdk Inhibitor Family, Is a Candidate Tumor Suppressor Gene. Genes Dev. 1995;9(6):650-62.

https://doi.org/10.1101/gad.9.6.650

Xiong Y, Hannon GJ, Zhang H, Casso D, Kobayashi R, Beach D. p21 Is a Universal Inhibitor of Cyclin Kinases. Nature. 1993;366(6456):701-4.

https://doi.org/10.1038/366701a0

Souto-García A, Fernández-Somoano A, Pascual T, Álvarez-Avellón SM, Tardón A. Association of p21 Ser31Arg and p53 Arg72Pro Polymorphisms with Lung Cancer Risk in CAPUA Study. Lung Cancer (Auckl). 2012;3:69-78.

https://doi.org/10.2147/LCTT.S35287

Betticher DC, Thatcher N, Altermatt HJ, Hoban P, Ryder WD, Heighway J. Alternate Splicing Produces a Novel Cyclin D1 Transcript. Oncogene. 1995;11(5):1005-11.

Tanić N, Milašin J, Dramićanin T, Bošković M, Vukadinović, M, Milošević V, Tanić N. TP53 and C-Myc Co-Alterations: a Hallmark of Oral Cancer Progression. J Med Biochem. 2013;32(4):380-8.

https://doi.org/10.2478/jomb-2014-0009

Xu HM, Xu LF, Hou TT, Luo LF, Chen GB, Sun XW, Lou XY. GMDR: Versatile Software for Detecting Gene-Gene and Gene-Environment Interactions Underlying Complex Traits. Curr Genomics. 2016;17(5):396-402.

https://doi.org/10.2174/1389202917666160513102612

Lou XY, Chen GB, Yan L, Ma JZ, Mangold JE, Zhu J, Elston R, Ming DL. A Combinatorial Approach to Detecting Gene-Gene and Gene-Environment Interactions in Family Studies. Am J Hum Genet. 2008;83(4):457-67.

https://doi.org/10.1016/j.ajhg.2008.09.001

Chen GB, Xu Y, Xu HM, Li MD, Zhu J, Lou XY. Practical and Theoretical Considerations in Study Design for Detecting Gene-Gene Interactions Using MDR and GMDR Approaches. PLoS One. 2011;6(2):e16981.

https://doi.org/10.1371/journal.pone.0016981

Karimian A, Ahmadi Y, Yousefi B. Multiple Functions of P21 in Cell Cycle, Apoptosis and Transcriptional Regulation after DNA Damage. DNA Repair. 2016;42:63-71.

https://doi.org/10.1016/j.dnarep.2016.04.008

Li G, Liu Z, Sturgis EM, Shi Q, Chamberlain RM, Spitz MR, Wei Q. Genetic Polymorphisms of P21 Are Associated With Risk of Squamous Cell Carcinoma of the Head and Neck. Carcinogenesis. 2005;26(9):1596-602.

https://doi.org/10.1093/carcin/bgi105

Holley SL, Matthias C, Jahnke V, Fryer AA, Strange RC, Hoban PR. Association of Cyclin D1 Polymorphism with Increased Susceptibility to Oral Squamous Cell Carcinoma. Oral Onc. 2005;41(2):156-60.

https://doi.org/10.1016/j.oraloncology.2004.08.005

Zheng Y, Shen H, Sturgis EM, Wang LE, Eicher SA, Strom SS, Frazier ML, Spitz MR, Wei Q. Cyclin D1 Polymorphism and Risk for Squamous Cell Carcinoma of the Head and Neck: a Case-Control Study. Carcinogenesis. 2001;22(8):1195-9.

https://doi.org/10.1093/carcin/22.8.1195

Thakur N, Kumari S, Mehrotra R. Association Between Cyclin D1 G870A (Rs9344) Polymorphism and Cancer Risk in Indian Population: Meta-Analysis and Trial Sequential Analysis. Biosci Rep. 2018;38(6):BSR20180694.

https://doi.org/10.1042/BSR20180694

Knudsen KE. The Cyclin D1b Splice Variant: an Old Oncogene Learns New Tricks. Cell Div. 2006;1:15.

https://doi.org/10.1186/1747-1028-1-15

Knudsen KE, Diehl JA, Haiman CA, Knudsen ES. Cyclin D1: Polymorphism, Aberrant Splicing and Cancer Risk. Oncogene. 2006;25(11):1620-8.

https://doi.org/10.1038/sj.onc.1209371

Ramos-García P, Gil-Montoya JA, Scully C, Ayén A, González-Ruiz L, Navarro-Triviño FJ, Gonzalez-Moles MA. An Update on the Implications of Cyclin D1 in Oral Carcinogenesis. Oral Dis. 2017;23(7):897-912.

https://doi.org/10.1111/odi.12620

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.

Gomes CC, Drummond SN, Guimarães AL, Andrade CI, Mesquita RA, Gomez RS. P21/ WAF1 and Cyclin D1 Variants and Oral Squamous Cell Carcinoma. J Oral Pathol Med. 2008;37(3):151-6.

https://doi.org/10.1111/j.1600-0714.2007.00604.x

Atac A, Riecke B, Assaf AT, Gröbe A, Friedrich RE, Heiland M, Izbicki JR, Kluwe L, Blessmann M. Lack of Evidence for Predictive and Prognostic Value of Cyclin D1 Gene Polymorphism CCND1 G870A for Oral Squamous Cell Carcinoma. Anticancer Res. 2014;34(1):235-8.

Wang L, Wang Z, Gao X, Li X, Sun X, Liu C. Association Between Cyclin D1 Polymorphism and Oral Cancer Susceptibility: a Meta-Analysis. Tumour Biol. 2014;35(2):1149-55.

https://doi.org/10.1007/s13277-013-1154-8

Zhuo XL, Ling JJ, Zhao HY, Zhou Y, Song YF, Tan YH. Lack of Association of the Cyclin D1 G870A Variation with Oral Carcinoma Risk: Evidence From 2,404 Subjects. Exp Ther Med. 2012;4(4):748-54.

https://doi.org/10.3892/etm.2012.648

Murali A, Varghese BT, Kumar RR, Kannan S. Combination of Genetic Variants in Cyclin D1 and Retinoblastoma Genes Predict Clinical Outcome in Oral Cancer Patients. Tumour Biol. 2016;37(3):3609-17.

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

Zhong S, Nukui T, Buch S, Diergaarde B, Weissfeld LA, Grandis J, Romkes M, Weissfeld JL. Effects of ERCC2 Lys751Gln (A35931C) and CCND1 (G870A) Polymorphism on Outcome of Advanced-Stage Squamous Cell Carcinoma of the Head and Neck are Treatment Dependent. Cancer Epidemiol Biomarkers Prev. 2011;20(11):2429-37.

https://doi.org/10.1158/1055-9965.EPI-11-0520

Karunakaran K, Muniyan R. Genetic Alterations and Alinical Aimensions of Oral Cancer: a Review. Molecular Biology Reports. 2020;47(11):9135-48.

https://doi.org/10.1007/s11033-020-05927-0

Li J, Li Z, Kan Q, Sun S, Li Y, Wang S. Association of p21 3' UTR Gene Polymorphism with Cancer Risk: Evidence from a Meta-analysis. Sci Rep. 2015;5:13189.

https://doi.org/10.1038/srep13189

Wang Z, Sturgis EM, Zhang F, Lei D, Liu Z, Xu L, Song X, Wei Q, Li G. 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.

https://doi.org/10.1186/1476-4598-11-17

Keshava C, Frye BL, Wolff MS, McCanlies EC, Weston A. Waf-1 (p21) and p53 Polymorphisms in Breast Cancer. Cancer Epidemiol Biomarkers Prev. 2002;11(1):127-30.

Jaiswal PK, Singh V, Mittal RD. Polymorphism at P21 codon 31 and Dinucleotide Polymorphism of P73 Gene and Susceptibility to Bladder Cancer in Individuals from North India. Indian J Hum Genet. 2013;19(3):293-300.

https://doi.org/10.4103/0971-6866.120815

Tsai MH, Chen WC, Tsai FJ. Correlation of p21 Gene Codon 31 Polymorphism and TNF-alpha Gene Polymorphism with Nasopharyngeal Carcinoma. J Clin Lab Anal. 2002;16(3):146-50. https://doi.org/10.1002/jcla.10032

Zintzaras E, Lau J. Synthesis of Genetic Association Studies for Pertinent Gene-Disease Associations Requires Appropriate Methodological and Statistical Approaches. JClin Epidemiol. 2008;61(7):634-45. https://doi.org/10.1016/j.jclinepi.2007.12.011

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Published

2021-12-15

How to Cite

1.
Jović S, Zeljić K, Ivković N, Štefik D, Kozomara R, Stošić S, Šupić G. Cyclin D1 and p21 gene variants and oral squamous cell carcinoma risk and prognosis. Arch Biol Sci [Internet]. 2021Dec.15 [cited 2022Dec.8];73(4):437-45. Available from: https://www.serbiosoc.org.rs/arch/index.php/abs/article/view/6911

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