Abstract
During the transformation process single nucleotide polymorphisms (SNPs) of key genes, such as p53 Arg72Pro or EGF A61G, may mediate various cellular processes. These variants may be associated with colorectal cancer risk (CRC), but conflicting findings have been reported. The purpose of this study was to determine the association of the SNPs in 5′ UTR of EGF A61G and p53 Arg72Pro and CRC in the Slovak population. The present case-control study was carried out in 173 confirmed CRC patients and 303 healthy subjects. Genotyping was performed by PCR-RFLP methods. Significant association was observed between age and CRC risk (p=0.001). Lower CRC risk was seen in younger patients carrying genotype p53 Arg72Pro (0.14; 95% CI 0.02–0.99, p=0.049). Gender-stratified analysis showed a significant inverse association of the polymorphism EGF G61G with CRC risk (0.48; 95% CI 0.2–0.9, p=0.04) only in male patients. Tumour site genotype distribution revealed that female patients with localized colon cancer were significantly associated with p53 Pro72Pro genotype (4.0; 95% CI 1.27–12.7, p=0.04) whereas the cancer of rectosigmoid junction was associated with the EGF G61G genotype (4.5; 95% CI 1.2–16.97, p=0.02). Combination of p53 Arg72Pro or EGF A61G polymorphisms were not associated with CRC risk by using logistic regression.
[1] Hezova R, et al. Common polymorphisms in GSTM1, GSTT1, GSTP1, GSTA1 and susceptibility to CRC the Central-European population. European Journal of Medical Research 17: 17, 2012 http://dx.doi.org/10.1186/2047-783X-17-1710.1186/2047-783X-17-17Search in Google Scholar PubMed PubMed Central
[2] Ferlay J, et al. Estimates of worldwide burden of cancer in 2008: Globocan 2008. Int J Cancer 127: 2893–2917, 2010 http://dx.doi.org/10.1002/ijc.2551610.1002/ijc.25516Search in Google Scholar PubMed
[3] Center MM, Jemal A and Ward, E. International Trends in Colorectal Cancer Incidence Rates. Cancer Epidemiol Biomarkers Prev 18: 1688, 2009 http://dx.doi.org/10.1158/1055-9965.EPI-09-009010.1158/1055-9965.EPI-09-0090Search in Google Scholar PubMed
[4] Aylon Y and Oren M. New plays in the p53 theatre. Curr. Opin. Genet Dev 21: 86–92, 2010 http://dx.doi.org/10.1016/j.gde.2010.10.00210.1016/j.gde.2010.10.002Search in Google Scholar PubMed PubMed Central
[5] Whibley C, Pharoah PDP and Hollstein M. p53 polymorphisms: cancer implications. Nature Reviews Cancer 9: 95–107, 2009 http://dx.doi.org/10.1038/nrc258410.1038/nrc2584Search in Google Scholar PubMed
[6] Katkoori VR, Jia X, Shanmugam C, Wan W, et al. Prognostic significance of p53 codon 72 polymorphism differs with race in colorectal adenocarcinoma. Clin Cancer Res 15: 2406–2416, 2009 http://dx.doi.org/10.1158/1078-0432.CCR-08-171910.1158/1078-0432.CCR-08-1719Search in Google Scholar PubMed PubMed Central
[7] Murphy ME. Polymorphic variants in the p53 pathway. Cell Death Differ 13: 916–920, 2006 http://dx.doi.org/10.1038/sj.cdd.440190710.1038/sj.cdd.4401907Search in Google Scholar PubMed
[8] Thomas M, Kalita A, Labrecque S, et al. Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol 19: 1092–100, 1999 10.1128/MCB.19.2.1092Search in Google Scholar PubMed PubMed Central
[9] Dumont P, Leu JI, Della PA, George DL, and Murphy M. The codon 72 polymorphic variants of p53 have markedly diff erent apoptotic potential. Nat Genet 33: 357–365, 2003 http://dx.doi.org/10.1038/ng109310.1038/ng1093Search in Google Scholar PubMed
[10] Sullivan A, Syed N, Gasco M et al. Polymorphism in wildtype p53 modulates response to chemotherapy in vitro and in vivo. Oncogene 23: 3328–3337, 2004 http://dx.doi.org/10.1038/sj.onc.120742810.1038/sj.onc.1207428Search in Google Scholar PubMed
[11] Gemignani F, Moreno V, Landi S et al. ATP53 polymorphism is associated with increased risk of CRC and with reduced levels of TP53 mRNA. Oncogene 23: 1954–1956, 2004 http://dx.doi.org/10.1038/sj.onc.120730510.1038/sj.onc.1207305Search in Google Scholar
[12] Zhu ZZ, Wang AZ, Jia HR et al. Association of the TP53 codon 72 polymorphism with CRC in a Chinese population. Jpn J Clin Oncol 37: 385–390, 2007 http://dx.doi.org/10.1093/jjco/hym03410.1093/jjco/hym034Search in Google Scholar
[13] Sameer AS, Shah ZA, Syeed N, et al. TP53 Pro47Ser and Arg72Pro polymorphisms and CRC predisposition in an ethnic Kashmiri population. Genet Mol Res 9: 651–660, 2010 http://dx.doi.org/10.4238/vol9-2gmr75110.4238/vol9-2gmr751Search in Google Scholar
[14] Själander A, Birgander R, Athlin L et al. P53 germ line haplotypes associated with increased risk for colorectal cancer. Carcinogenesis 16: 1461–1464, 1995 http://dx.doi.org/10.1093/carcin/16.7.146110.1093/carcin/16.7.1461Search in Google Scholar
[15] Sayhan N, Yazici H, Budak M, et al. P53 codon 72 genotypes in colon cancer. Association with human papillomavirus infection. Res Commun Mol Pathol Pharmacol 109: 25–34, 2001 Search in Google Scholar
[16] Hamajima N, Matsuo K, Suzuki T, et al. No associations of p73 G4C14-to-A4T14 at exon 2 and p53 Arg72Pro polymorphisms with the risk of digestive tract cancers in Japanese. Cancer Lett 181: 81–5, 2002 http://dx.doi.org/10.1016/S0304-3835(02)00041-110.1016/S0304-3835(02)00041-1Search in Google Scholar
[17] Schneider-Stock R, Boltze C, Peters B, et al. Selective loss of codon 72 proline p53 and frequent mutational inactivation of the retained arginine allele in CRC. Neoplasia 6: 529–535, 2004 http://dx.doi.org/10.1593/neo.0417810.1593/neo.04178Search in Google Scholar
[18] Pérez LO, Abba MC, Dulout FN et al. Evaluation of p53 codon 72 polymorphismin adenocarcinomas of the colon and rectum in La Plata, Argentina. World J Gastroenterol 12: 1426–1429, 2006 10.3748/wjg.v12.i9.1426Search in Google Scholar
[19] Economopoulos KP, Sergentanis TN, Zagouri F, et al. Association between p53 Arg72Pro polymorphism and CRC risk: a meta-analysis. Onkologie 33: 666–74, 2010 http://dx.doi.org/10.1159/00032221010.1159/000322210Search in Google Scholar
[20] Sucheston L, et al. Natural selection and functional genetic variation in the p53 pathway. Hum Mol Genet 20: 1502–1508, 2011 http://dx.doi.org/10.1093/hmg/ddr02810.1093/hmg/ddr028Search in Google Scholar
[21] Alroy I and Yarden Y. The ErbB signaling network in embryogenesis and oncogenesis: signal diversification through combinatorial ligand-receptor interactions. FEBS Lett: 410: 83–86, 1997 http://dx.doi.org/10.1016/S0014-5793(97)00412-210.1016/S0014-5793(97)00412-2Search in Google Scholar
[22] Burgering BM and Coffer PJ. Protein kinase B (c-Akt) in phosphatidylinositol-3-OH kinase signal transduction. Nature 376: 599–602, 1995 http://dx.doi.org/10.1038/376599a010.1038/376599a0Search in Google Scholar
[23] Chan TO, Rittenhouse SE and Tsichlis PN. AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation. Annu Rev Biochem 68: 965–1014, 1999 http://dx.doi.org/10.1146/annurev.biochem.68.1.96510.1146/annurev.biochem.68.1.965Search in Google Scholar
[24] Llorens F, Hummel M, Pastor X, et al. Multiple platform assessment of the EGF dependent transcriptome by microarray and deep tag sequencing analysis. BMC Genomics 12: 326, 2011 http://dx.doi.org/10.1186/1471-2164-12-32610.1186/1471-2164-12-326Search in Google Scholar
[25] Petit AM, et al. Neutralizing antibodies against EGF and ErbB-2/neu receptor tyrosine kinases down-regulate vascular endothelial growth factor production by tumor cells in vitro and in vivo: angiogenic implications for signal transduction therapy of solid tumors. Am J Pathol 151: 1523–1530, 1997 Search in Google Scholar
[26] Nicholson S, et al. EGFR results of a 6 year followup study in operable breast cancer with emphasis on the node negative subgroup. Br J Cancer. 1991 January; 63(1): 146–150 http://dx.doi.org/10.1038/bjc.1991.3010.1038/bjc.1991.30Search in Google Scholar
[27] Scagliotti GV, Selvaggi G, Novello S, Hirsch FR. The biology of EGFR in lung cancer. Clin Cancer Res 10, 2004. 10.1158/1078-0432.CCR-040007Search in Google Scholar
[28] Obradovic J, Jurisic V. Evaluation of current methods to detect the mutations of EGFR in non-small cell lung cancer patients. Multidiscip Respir Med. 2012 Dec 11;7(1):52 http://dx.doi.org/10.1186/2049-6958-7-5210.1186/2049-6958-7-52Search in Google Scholar
[29] Messa C, Russo F, Caruso MG et al. EGF, TGF-alpha and EGFR in human colorectal adenocarcinoma. Acta Oncol 37: 285–289, 1998 http://dx.doi.org/10.1080/02841869842959510.1080/028418698429595Search in Google Scholar
[30] Shahbazi M, Pravica V, Nasreen N et al. Association between functional polymorphism in EGF gene and malignant melanoma. Lancet 359: 397–401, 2002 http://dx.doi.org/10.1016/S0140-6736(02)07600-610.1016/S0140-6736(02)07600-6Search in Google Scholar
[31] Hamai Y, Matsumura S, Matsusaki K, et al. A single nucleotide polymorphism in the 5′ untranslated region of the EGF gene is associated with occurrence and malignant progression of gastric cancer. Pathobiology 72: 133–8, 2005 http://dx.doi.org/10.1159/00008411610.1159/000084116Search in Google Scholar PubMed
[32] Goto Y, Ando T, Goto H and Hamajima N. No association between EGF gene polymorphism and gastric cancer. Cancer Epidemiol Biomarkers Prev 14: 2454–6, 2005 http://dx.doi.org/10.1158/1055-9965.EPI-05-040110.1158/1055-9965.EPI-05-0401Search in Google Scholar PubMed
[33] Costa BM, Ferreira P, Costa S, et al. Association between functional EGF G61A polymorphism and glioma risk. Clin Cancer Res 13: 2621–2626, 2007 http://dx.doi.org/10.1158/1078-0432.CCR-06-260610.1158/1078-0432.CCR-06-2606Search in Google Scholar PubMed
[34] Tanabe KK, Lemoine A, Finkelstein DM, et al. EGF gene functional polymorphism and the risk of hepatocellular carcinoma in patients with cirrhosis. JAMA 299: 53–60, 2008 http://dx.doi.org/10.1001/jama.2007.6510.1001/jama.2007.65Search in Google Scholar PubMed
[35] Wu GC, Hasenberg T, Magdeburg R, et al. Association Between EGF, TGF-b1, VEGF gene polymorphism and colorectal cancer. World J Surg 33: 124–129, 2009 http://dx.doi.org/10.1007/s00268-008-9784-510.1007/s00268-008-9784-5Search in Google Scholar PubMed
[36] Kovar FM, Thallinger C, Marsik CL, et al. The EGF 61A/G polymorphism-a predictive marker for recurrence of liver metastases from CRC. Wien Klin Wochenschr 121: 638–643, 2009 http://dx.doi.org/10.1007/s00508-009-1250-310.1007/s00508-009-1250-3Search in Google Scholar PubMed
[37] Tenti P, et al. p53 codon 72 polymorphism does not affect the risk of cervical cancer in patients from Northern Italy. Cancer Epidemiol Biomarkers Prev 9: 435–438, 2000 Search in Google Scholar
[38] Scheckenbach K, et al. Cancer Epidemiol Biomarkers Prev 13: 1805–1809, 2004 10.1158/1055-9965.1805.13.11Search in Google Scholar
[39] Santos LE, Guilhen AC, de Andrade RA, et al. The role of TP53 Pro47Ser and Arg72Pro SNPs in the susceptibility to bladder cancer. Urol Oncol 29: 291–294, 2011 http://dx.doi.org/10.1016/j.urolonc.2009.03.02610.1016/j.urolonc.2009.03.026Search in Google Scholar PubMed
[40] Srivastava P, Jaiswal PK, Singh V, et al.: Role of p53 gene polymorphism and bladder cancer predisposition in northern India. Cancer Biomark 8: 21–28, 2010 10.3233/DMA-2011-0816Search in Google Scholar PubMed
[41] Zorića A, Horvat A, Balija M and Slade N. The Arg72Pro Polymorphism of TP53 in Croatian Population. Croat Chem Acta 85: 239–243, 2012 http://dx.doi.org/10.5562/cca186610.5562/cca1866Search in Google Scholar
[42] Aizat AA, Shahpudin SN, Mustapha MA, et al. Association of Arg72Pro of P53 polymorphism with CRC susceptibility risk in Malaysian population. Asian Pac J Cancer Prev 12: 2909–2913, 2011 Search in Google Scholar
[43] Cao Z, Song JH, Park YK et al. The p53 codon 72 polymorphism and susceptibility to CRC in Korean patients. Neoplasma 56: 114–118, 2009 http://dx.doi.org/10.4149/neo_2009_02_11410.4149/neo_2009_02_114Search in Google Scholar PubMed
[44] Eren F, Akkiprik M, Atuğ Ö, et al. R72P Polymorphism of TP53 in Ulcerative Colitis Patients is Associated with the Incidence of Colectomy, Use of Steroids and the Presence of a Positive Family History. Pathol Oncol Res 16: 563–568, 2010 http://dx.doi.org/10.1007/s12253-010-9255-910.1007/s12253-010-9255-9Search in Google Scholar PubMed
[45] Tang NP, Wu YM, Wang B, Ma J. Systematic review and meta-analysis of the association between P53 codon 72 polymorphism and CRC. Eur J Surg Oncol 36: 431–438, 2010 http://dx.doi.org/10.1016/j.ejso.2010.03.01010.1016/j.ejso.2010.03.010Search in Google Scholar PubMed
[46] Denisov EV, Cherdyntseva NV, Litviakov NV, et al. TP53 Gene Polymorphisms in Cancer Risk: The Modulating Effect of Ageing, Ethnicity and TP53 Somatic Abnormalities, Tumor Suppressor Genes, Dr. Yue Cheng (Ed.), ISBN: 978-953-307-879-3, 2012 Search in Google Scholar
[47] Brozek W, Krivwanek S, Bonner E, et al. Mutual Associations between Malignancy, Age, Gender, and Subsite Incidence of CRC. Anticancer research 29: 3721–3726, 2009 Search in Google Scholar
[48] Troisi RJ, Freedman AN, Devesa SS. Incidence of colorectal carcinoma in the U.S.: an update of trends by gender, race, age, subsite and stage, 1975–1994. Cancer 85: 1670–1676, 1999 http://dx.doi.org/10.1002/(SICI)1097-0142(19990415)85:8<1670::AID-CNCR5>3.0.CO;2-M10.1002/(SICI)1097-0142(19990415)85:8<1670::AID-CNCR5>3.0.CO;2-MSearch in Google Scholar
[49] Austoker J. Screening for colorectal cancer. BMJ 309: 382–386, 1994 http://dx.doi.org/10.1136/bmj.309.6951.38210.1136/bmj.309.6951.382Search in Google Scholar
[50] Mates IN, et al. Single Nucleotide Polymorphisms in CRC: Associations with Tumor Site and TNM Stage. J Gastrointestin Liver Dis 21: 45–52, 2012 Search in Google Scholar
[51] Vogelstein B and Kinzler KW. Cancer genes and the pathways they control. Nat Med 10: 789–799, 2004 http://dx.doi.org/10.1038/nm108710.1038/nm1087Search in Google Scholar
[52] Gervaz P, Bucher P and Morel P. Two colons-two cancers: paradigm shift and clinical implications. J Surg Oncol 88: 261–266, 2004 http://dx.doi.org/10.1002/jso.2015610.1002/jso.20156Search in Google Scholar
[53] Koushik A, Tranah GJ, Ma J, et al. p53 Arg72Pro polymorphism and risk of colorectal adenoma and cancer. Int J Cancer 119: 1863–1868, 2006 http://dx.doi.org/10.1002/ijc.2205710.1002/ijc.22057Search in Google Scholar
[54] Dakouras A, Nikiteas N, Papadakis E, et al. P53Arg72 homozygosity and its increased incidence in left-sided sporadic colorectal adenocarcinomas, in a Greek-Caucasian population. Anticancer Res 28: 1039–1043, 2008 Search in Google Scholar
[55] Olschwang S, Laurent-Puig P, Vassal A, et al. Characterization of a frequent polymorphism in the coding sequence of the TP53 gene in colonic cancer patients and a control population. Hum Genet 86: 369–370, 1991 http://dx.doi.org/10.1007/BF0020183610.1007/BF00201836Search in Google Scholar
[56] Koenders PG, Peters WH, Wobbes T, et al. EGFR levels are lower in carcinomatous than in normal CRC tissue. Br J Cancer 65: 189–192, 1992 http://dx.doi.org/10.1038/bjc.1992.3910.1038/bjc.1992.39Search in Google Scholar
[57] Spindler KL, Nielsen JN, Ornskov D, et al. EGF A61G polymorphism and EGF gene expression in normal colon tissue from patients with CRC. Acta Oncol 46: 1113–1117, 2007 http://dx.doi.org/10.1080/0284186070133885310.1080/02841860701338853Search in Google Scholar
[58] Lanuti M, et al. A functional EGF polymorphism, EGF serum levels, and esophageal adenocarcinoma risk and outcome. Clin Cancer Res 14: 3216–3222, 2008 http://dx.doi.org/10.1158/1078-0432.CCR-07-493210.1158/1078-0432.CCR-07-4932Search in Google Scholar
[59] Graziano F, Ruzzo A, Loupakis F, et al. Pharmacogenetic profiling for cetuximab plus irinotecan therapy in patients with refractory advanced CRC. J Clin Oncol 26(9): 1427–1434, 2008 http://dx.doi.org/10.1200/JCO.2007.12.460210.1200/JCO.2007.12.4602Search in Google Scholar
[60] Lurje G, et al. Polymorphisms in cyclooxygenase-2 and EGFR are associated with progression-free survival independent of K-ras in metastatic CRC patients treated with single-agent cetuximab. Clin Cancer Res 14: 7884–7895, 2008 http://dx.doi.org/10.1158/1078-0432.CCR-07-516510.1158/1078-0432.CCR-07-5165Search in Google Scholar PubMed
[61] Lurje G, et al. Genetic variations in angiogenesis pathway genes predict tumor recurrence in localized adenocarcinoma of the esophagus. Ann Surg 251: 857–864, 2010 http://dx.doi.org/10.1097/SLA.0b013e3181c97fcf10.1097/SLA.0b013e3181c97fcfSearch in Google Scholar PubMed
[62] Lieskovan S, Vallbohmer D, Zhang W, et al.: EGF61 Polymorphism Predicts Complete Pathologic Response to Cetuximab-Based Chemoradiation Independent of KRAS Status in Locally Advanced Rectal Cancer Patients. Clin Cancer Res, 2011 10.1158/1078-0432.CCR-10-2666Search in Google Scholar PubMed PubMed Central
© 2014 Versita Warsaw
This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.
