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Published in: Medical Oncology 7/2014

01-07-2014 | Original Paper

Investigation of the association of hRRM1 and p53R2 gene polymorphisms in head and neck squamous cell carcinomas

Authors: Kadir Serkan Orhan, Ender Coskunpinar, Deniz Kanliada, Yasemin Musteri Oltulu, Bora Basaran, Mehmet Celik, Bedia Cakmakoglu, Kemal Deger

Published in: Medical Oncology | Issue 7/2014

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Abstract

Head and neck squamous epithelial cell cancer (HNSCC), the world’s fifth most common type of cancers, is associated with short life expectancy and high death rates if not detected in early stages. The aim of this study was to investigate hRRM1 and p53R2 gene polymorphisms by using real-time PCR technique in patients with head and neck cancer. In total, 87 patients with head and neck malignancies and 87 control group who have not any malignancies were included in the study between January 2011 and February 2012 in Istanbul University Faculty of Medicine Department of ORL. In the study, real-time PCR was used to detect hRRM1 (rs12806698 C/A) and p53R2 (rs2290707 G/T) gene polymorphisms in Turkish HNSCC patients and healthy individuals. Genomic DNA isolation was performed according to the kit protocol with spin column. LightCycler 1.5 system was used to perform SNP genotyping using hybridization probes consisting of 3′-fluorescein and a 5′-LightCycler Red labeled pair of oligonucleotide probes. There were significant differences in the distribution of hRRM1 genotypes. Frequency of individuals with hRRM1 AA genotype was higher in patients with less differentiation when compared with well differentiation [p 0.025, Fisher’s exact test, odds ratio (OR) 0.140, 95 % confidence intervals (CI) 0.024–0.797]. It is observed that A allele carriers have nearly twofold risk for development of the disease (p = 0.022; χ 2 5.24; OR 2.02, 95 % CI 1.10–3.72).
Literature
1.
go back to reference Marcu LG, Yeoh E. A review of risk factors and genetic alterations in head and neck carcinogenesis and implications for current and future approaches to treatment. J Cancer Res Clin Oncol. 2009;135(10):1303–14.PubMedCrossRef Marcu LG, Yeoh E. A review of risk factors and genetic alterations in head and neck carcinogenesis and implications for current and future approaches to treatment. J Cancer Res Clin Oncol. 2009;135(10):1303–14.PubMedCrossRef
2.
go back to reference Liu BQ, Peto R, Chen ZM, Boreham J, Wu YP, et al. Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths. Br Med J. 1998;317:1411–22.CrossRef Liu BQ, Peto R, Chen ZM, Boreham J, Wu YP, et al. Emerging tobacco hazards in China: 1. Retrospective proportional mortality study of one million deaths. Br Med J. 1998;317:1411–22.CrossRef
3.
go back to reference Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med. 1993;328:184–94.PubMedCrossRef Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med. 1993;328:184–94.PubMedCrossRef
4.
go back to reference Maier H, Dietz A, Gewelke U, Heller WD, Weidauer H. Tobacco, alcohol and the risk of head and neck cancer. Clin Invest. 1992;70:320–7. Maier H, Dietz A, Gewelke U, Heller WD, Weidauer H. Tobacco, alcohol and the risk of head and neck cancer. Clin Invest. 1992;70:320–7.
6.
go back to reference Jaber MA. Oral epithelial dysplasia in non-users of tobacco and alcohol: an analysis of clinicopathologic characteristics and treatment outcome. J Oral Sci. 2010;52(1):13–21.PubMedCrossRef Jaber MA. Oral epithelial dysplasia in non-users of tobacco and alcohol: an analysis of clinicopathologic characteristics and treatment outcome. J Oral Sci. 2010;52(1):13–21.PubMedCrossRef
7.
go back to reference Ashraf MJ, Maghbul M, Azarpira N, Khademi B. Expression of Ki67 and P53 in primary squamous cell carcinoma of the larynx. Indian J Pathol Microbiol. 2010;53(4):661–5.PubMedCrossRef Ashraf MJ, Maghbul M, Azarpira N, Khademi B. Expression of Ki67 and P53 in primary squamous cell carcinoma of the larynx. Indian J Pathol Microbiol. 2010;53(4):661–5.PubMedCrossRef
8.
go back to reference Chen X, Bargonetti J, Prives C. p53, through p21 (WAF1/CIP1), induces cyclin D1 synthesis. Cancer Res. 1995;55:4257–63.PubMed Chen X, Bargonetti J, Prives C. p53, through p21 (WAF1/CIP1), induces cyclin D1 synthesis. Cancer Res. 1995;55:4257–63.PubMed
9.
go back to reference Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, et al. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature. 2000;404:42–9.PubMedCrossRef Tanaka H, Arakawa H, Yamaguchi T, Shiraishi K, Fukuda S, et al. A ribonucleotide reductase gene involved in a p53-dependent cell-cycle checkpoint for DNA damage. Nature. 2000;404:42–9.PubMedCrossRef
10.
go back to reference Yamaguchi T, Matsuda K, Sagiya Y, Iwadate M, Fujino MA. p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint. Cancer Res. 2001;61:8256–62.PubMed Yamaguchi T, Matsuda K, Sagiya Y, Iwadate M, Fujino MA. p53R2-dependent pathway for DNA synthesis in a p53-regulated cell cycle checkpoint. Cancer Res. 2001;61:8256–62.PubMed
11.
go back to reference Nakano K, Balint E, Ashcrof M, Vousden KH. A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene. 2000;19:4283–9.PubMedCrossRef Nakano K, Balint E, Ashcrof M, Vousden KH. A ribonucleotide reductase gene is a transcriptional target of p53 and p73. Oncogene. 2000;19:4283–9.PubMedCrossRef
12.
go back to reference Kauppi B, Nielsen BB, Ramaswamy S, Larsen IK, Thelander M, et al. The three-dimensional structure of mammalian ribonucleotide reductase protein R2 reveals a more-accessible iron-radical site than Escherichia coli R2. J Mol Biol. 1996;262:706–20.PubMedCrossRef Kauppi B, Nielsen BB, Ramaswamy S, Larsen IK, Thelander M, et al. The three-dimensional structure of mammalian ribonucleotide reductase protein R2 reveals a more-accessible iron-radical site than Escherichia coli R2. J Mol Biol. 1996;262:706–20.PubMedCrossRef
13.
go back to reference Rova U, Adrait A, Potsch S, Graslund A, Thelander L. Evidence by mutagenesis that Tyr370 of the mouse ribonucleotide reductase R2 protein is the connecting link in the intersubunit radical transfer pathway. J Biol Chem. 1999;274:23746–51.PubMedCrossRef Rova U, Adrait A, Potsch S, Graslund A, Thelander L. Evidence by mutagenesis that Tyr370 of the mouse ribonucleotide reductase R2 protein is the connecting link in the intersubunit radical transfer pathway. J Biol Chem. 1999;274:23746–51.PubMedCrossRef
15.
16.
go back to reference Jordheim LP, Sève P, Trédan O, Dumontet C. The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer. Lancet Oncol. 2011;12(7):693–702.PubMedCrossRef Jordheim LP, Sève P, Trédan O, Dumontet C. The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer. Lancet Oncol. 2011;12(7):693–702.PubMedCrossRef
17.
go back to reference Qiu W, Zhou B, Darwish D, Shao J, Yen Y. Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits. Biochem Biophys Res Commun. 2006;340(2):428–34.PubMedCrossRef Qiu W, Zhou B, Darwish D, Shao J, Yen Y. Characterization of enzymatic properties of human ribonucleotide reductase holoenzyme reconstituted in vitro from hRRM1, hRRM2, and p53R2 subunits. Biochem Biophys Res Commun. 2006;340(2):428–34.PubMedCrossRef
18.
go back to reference Kosaka Y, Mimori K, Fukagawa T, Ishikawa K, Etoh T, et al. Clinical significance of molecular detection of matrix metalloproteinase-1 in bone marrow and peripheral blood in patients with gastric cancer. Ann Surg Oncol. 2012;19(3):430–7.CrossRef Kosaka Y, Mimori K, Fukagawa T, Ishikawa K, Etoh T, et al. Clinical significance of molecular detection of matrix metalloproteinase-1 in bone marrow and peripheral blood in patients with gastric cancer. Ann Surg Oncol. 2012;19(3):430–7.CrossRef
19.
go back to reference Ekmekçi A, Konaç E, Önen HI. Gen polimorfizmi ve kansere yatkınlık. Marmara Med J. 2008;21(3):282–95. Ekmekçi A, Konaç E, Önen HI. Gen polimorfizmi ve kansere yatkınlık. Marmara Med J. 2008;21(3):282–95.
20.
go back to reference Kolberg M, Strand KR, Graff P, Andersson KK. Structure, function, and mechanism of ribonucleotide reductases. Biochim Biophys Acta. 2004;1699:1–34.PubMedCrossRef Kolberg M, Strand KR, Graff P, Andersson KK. Structure, function, and mechanism of ribonucleotide reductases. Biochim Biophys Acta. 2004;1699:1–34.PubMedCrossRef
21.
go back to reference Fan H, Huang A, Villegas C, Wright JA. The R1 component of mammalian ribonucleotide reductase has malignancy-suppressing activity as demonstrated by gene transfer experiments. Proc Natl Acad Sci USA. 1997;94:13181–6.PubMedCentralPubMedCrossRef Fan H, Huang A, Villegas C, Wright JA. The R1 component of mammalian ribonucleotide reductase has malignancy-suppressing activity as demonstrated by gene transfer experiments. Proc Natl Acad Sci USA. 1997;94:13181–6.PubMedCentralPubMedCrossRef
22.
go back to reference Zhou BS, Tsai P, Ker R, Tsai J, Ho R, et al. Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential. Clin Exp Metastasis. 1998;16:43–9.PubMedCrossRef Zhou BS, Tsai P, Ker R, Tsai J, Ho R, et al. Overexpression of transfected human ribonucleotide reductase M2 subunit in human cancer cells enhances their invasive potential. Clin Exp Metastasis. 1998;16:43–9.PubMedCrossRef
23.
go back to reference Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006;24:4731–7.PubMedCrossRef Bepler G, Kusmartseva I, Sharma S, Gautam A, Cantor A, et al. RRM1 modulated in vitro and in vivo efficacy of gemcitabine and platinum in non-small-cell lung cancer. J Clin Oncol. 2006;24:4731–7.PubMedCrossRef
24.
go back to reference Gautam A, Bepler G. Suppression of lung tumor formation by the regulatory subunit of ribonucleotide reductase. Cancer Res. 2006;66:6497–502.PubMedCrossRef Gautam A, Bepler G. Suppression of lung tumor formation by the regulatory subunit of ribonucleotide reductase. Cancer Res. 2006;66:6497–502.PubMedCrossRef
25.
go back to reference Bepler G, Sharma S, Cantor A, Gautam A, Haura E, et al. RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol. 2004;22:1878–85.PubMedCrossRef Bepler G, Sharma S, Cantor A, Gautam A, Haura E, et al. RRM1 and PTEN as prognostic parameters for overall and disease-free survival in patients with non-small-cell lung cancer. J Clin Oncol. 2004;22:1878–85.PubMedCrossRef
26.
go back to reference Bepler G, Gautam A, McIntyre LM, Beck AF, Chervinsky DS, et al. Prognostic significance of molecular genetic aberrations on chromosome segment 11p15.5 in non-small-cell lung cancer. J Clin Oncol. 2002;20:1353–60.PubMedCrossRef Bepler G, Gautam A, McIntyre LM, Beck AF, Chervinsky DS, et al. Prognostic significance of molecular genetic aberrations on chromosome segment 11p15.5 in non-small-cell lung cancer. J Clin Oncol. 2002;20:1353–60.PubMedCrossRef
27.
go back to reference Sato J, Kimura T, Saito T, Anazawa T, Kenjo A, et al. Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2011;18:700–11.PubMedCrossRef Sato J, Kimura T, Saito T, Anazawa T, Kenjo A, et al. Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma. J Hepatobiliary Pancreat Sci. 2011;18:700–11.PubMedCrossRef
28.
go back to reference Zhang K, Wu J, Wu X, Wang X, Wang Y, et al. p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest. Mol Cancer Ther. 2011;10(2):269–78.PubMedCentralPubMedCrossRef Zhang K, Wu J, Wu X, Wang X, Wang Y, et al. p53R2 inhibits the proliferation of human cancer cells in association with cell-cycle arrest. Mol Cancer Ther. 2011;10(2):269–78.PubMedCentralPubMedCrossRef
29.
go back to reference Okumura H, Natsugoe S, Yokomakura N, Kita Y, Matsumoto M, et al. Expression of p53R2 is related to prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 2006;12(12):3740–5.PubMedCrossRef Okumura H, Natsugoe S, Yokomakura N, Kita Y, Matsumoto M, et al. Expression of p53R2 is related to prognosis in patients with esophageal squamous cell carcinoma. Clin Cancer Res. 2006;12(12):3740–5.PubMedCrossRef
Metadata
Title
Investigation of the association of hRRM1 and p53R2 gene polymorphisms in head and neck squamous cell carcinomas
Authors
Kadir Serkan Orhan
Ender Coskunpinar
Deniz Kanliada
Yasemin Musteri Oltulu
Bora Basaran
Mehmet Celik
Bedia Cakmakoglu
Kemal Deger
Publication date
01-07-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 7/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0012-x

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