Meme Kanserinde TP53 (RS1042522) Polimorfizmi

Year 2016, Volume: 2 Issue: 1, 28 - 31, 31.01.2016

Nihal Üren Tuğcan Korak Duygu Altınok Emel Ergül Bahadır Güllüoğlu Turgay Şimşek Zafer Cantürk Zafer Utkan Ali Sazcı

https://doi.org/10.30934/kusbed.358489

Cited By: 1

Abstract

Amaç: TP53 geni temel olarak DNA tamiri, apoptozis, hücre yaşlanması ve hücre döngüsü kontrolünde görev alan en önemli tümör baskılayıcı genlerden biridir. TP53 rs1042522 (Arg72Pro) polimorfizmi tümör baskılama sırasında P53 protein yapısında değişikliğe neden olan bir polimorfizmdir. Bu verilere dayanarak, bu çalışmanın amacı TP53 rs1042522 polimorfizmi ve meme kanseri riski arasındaki ilişkiyi araştırmaktır.

Yöntem: TP53 rs1042522 polimorfizmi için 508 meme kanserli kadın hastadan ve 367 sağlıklı kadından alınan periferik kanlardan DNA izole edilerek PCR-RFLP yöntemi ile genotipleme yapıldı. İstatistiksel analiz, %95 güven aralığında χ2 testi ile yapıldı ve Hardy-Weinberg eşitliği (HWE) test edilen hastalar ve kontrol popülasyonu için doğrulandı.

Bulgular: Genotip frekansları sırasıyla hasta ve kontrollerde GG alleli için %48.6, %46.3, GC alleli için %40.7, %44.7ve CC alleli için de %10.6, %9.0 şeklindedir. Vaka ve control genotipleri arasında istatistiksel olarak fark olmadığı bulundu (χ2=1.591, P= 0.451). Allel frekansı G alleli için vakalarda %69.0 ve kontrollerde %69.0, C alleli için vakalarda %31.0 kontrollerde %31.0 şeklinde ortaya çıktı. Sonuçlar istatistiksel olarak anlamsız bulundu (G allel: p=0.424, C allel: p=0.501). TP53 rs1042522 genotip dağılımı kontrol popülasyonu için Hardy-Weinberg eşitliğine göre kararlı bulundu (p>0.05).

Sonuç: Çalışmamızda meme kanseri ile p53 geninde yer alan rs1042522 polimorfizminin tek başına değerlendirildiğinde meme kanseri riski ile ilişkisi olmadığı bulunmuştur. P53’ün karsinogenezdeki rolünden ve özellikle de programlı hücre ölümünden sorumlu çeşitli proteinlerle etkileşime girmesinden dolayı rs1042522 polimorfizmini diğer proteinlerdeki değişimlerle birlikte çalışmak daha anlamlı olabilir. Ayrıca, farklı TP53 polimorfizmleri ile hücre döngüsünde görevli siklin, sikline bağımlı kinazlar ve p21 gibi genlerin ortak etkilerine odaklanılabilinir ya da bu polimorfizmin daha geniş bir hasta popülasyonunda tümörlerin klinikopatolojik özellikleri ile birlikte değerlendirilmesi daha anlamlı sonuçlar verebilir.

Keywords

P53 geni, rs1042522, polimorfizm, meme kanseri

TP53 (RS1042522) Polymorphism In Breast Cancer

Abstract

Objectives: TP53 gene is one of the most important tumour suppressor gene that mainly plays a role in DNA repair, cell apoptosis, cell senescence and cell cycle control. TP53 rs1042522 (Arg72Pro) polymorphism is nonsynonymous polymorphism that alters P53 protein capacity during tumour suppression. Based on the data above, the purpose of this study is to investigate association between TP53 rs1042522 polymorphism and breast cancer risk in hospital-based Turkish women population.

Methods: After DNA isolation from peripheral blood of 508 breast cancer patients and 367 healthy women the genotyping for TP53 rs1042522 polymorphism in both groups was done by a PCR-RFLP method. Statistical analysis was done by the χ2 test with 95% confidence intervals and the Hardy-Weinberg equilibrium was confirmed for tested patient and control populations.

Results: Genotype frequencies were 48.6%, 46.3% for GG, 40.7%, 44.7% for GC and 10.6%, 9.0% for CC in breast cancer and controls, respectively. There was not statistical difference between genotypes in cases and controls (χ2=1.591, P= 0.451). Allele frequencies for G allele were 69.0% in cases and 69.0% in controls, for C allele 31.0% in cases and 31.0 % in controls. Also, this results were found to be not statistically significant for G and C alleles (G allele: p=0.424, C allele: p=0.501). The distribution of TP53 rs1042522 genotypes was in agreement with HWE for controls (p>0.05).

Conclusion: There is no statistically significant association between rs1042522 and the risk of breast cancer in studied hospital- based Turkish women population. For further, rs1042522 polymorphism may be associated with other genetic factors due to the interaction of p53 with various proteins that play role in programmed cell death. Also, the combined effect of TP53 polymorphisms and the genes such as cyclins, cyclin-dependent kinases and p21 which are related with cell cycle control can be studied or clinicopathological characteristics of breast cancer patients might be evaluated in terms of p53 rs1042522 genotypes in larger population size.

Keywords

P53 gene, rs1042522, polymorphism, breast cancer

References

• Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011; 61: 69–90.
• Zhang YX, Wang XM, Kang S, et al. Common variants in the PALB2 gene confer susceptibility to breast cancer: a meta-analysis. APJCP. 2013; 14: 7149-54.
• Özmen V. Breast Cancer In The World and Turkey, J Breast Health, 2008; 4: 7-12
• Lu J, Wei Q, Bondy ML et al. Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <or=55 years. Carcinogenesis. 2006; 27(11): 2209-16.
• Saadatian Z, Gharesouran J, Ghojazadeh M et al. Association of rs1219648 in FGFR2 and rs1042522 in TP53 with Premenopausal Breast Cancer in an Iranian Azeri Population. Asian Pac J Cancer Prev. 2014; 15(18): 7955-7958.
• Ergul E, Sazci A. Molecular Genetics of Breast Cancer. Turk J Med Sci, 31; 2001: 1-14.
• Ebner F, Schremmer-Danninger E, Rehbock J. The role of TP53 and p21 gene polymorphisms in breast cancer biology in a well specified and characterized German cohort. J Cancer Res Clin Oncol. 2010; 136: 1369–75.
• Hamaguchi M, Nishio M, Toyama T et al. Possible Difference in Frequencies of Genetic Polymorphisms of Estrogen Receptor a, Estrogen Metabolism and P53 GenesBetween Estrogen Receptor-positive and -negative Breast Cancers. Jpn J Clin Oncol. 2008; 38(11): 734–42.
• Vymetalkova V, Soucek P, Kunicka T et al. Genotype and Haplotype Analyses of TP53 Gene in Breast Cancer Patients: Association with Risk and Clinical Outcomes. PLoS ONE. 2015; 10(7): e0134463.
• Dahabreh IJ, Schmid CH, Lau J et al. Genotype Misclassification in Genetic Association Studies of the rs1042522TP53 (Arg72Pro) Polymorphism: A Systematic Review of Studies of Breast,Lung, Colorectal, Ovarian, and Endometrial Cancer. Am J Epidemiol. 2013; 15; 177(12): 1317-25.
• Dumont P, Leu JI, Della Pietra AC et al. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genetics. 2003; 33(3): 357-65.
• Dahabreh IJ, Schmid CH, Lau J et al. Genotype misclassification in genetic association studies of the rs1042522 TP53 (Arg72Pro) polymorphism: a systematic review of studies of breast, lung, colorectal, ovarian, and endometrial cancer. Am J Epidemiol. 2013; 177: 1317–25.
• Cheng H, Ma B, Jiang R et al. Individual and combined effects ofMDM2 SNP309 and TP53 Arg72Pro on breast cancer risk: an updated meta-analysis. Mol Biol Rep. 2012; 39: 9265–74.
• Hu Z, Li X, Yuan R, et al. Three common TP53polymorphisms in susceptibility to breast cancer, evidencefrom meta-analysis. Breast Cancer Res Treat. 2010; 120: 705-14.
• He XF, Su J, Zhang Y, et al. Association between the p53polymorphisms and breast cancer risk: meta-analysis basedon case-control study. Breast Cancer Res Treat. 2011; 130: 517-29.
• Buyru N, Tigli H, Dalay N. P53 codon 72 polymorphism in breast cancer. Oncol Rep. 2003; 10: 711–14.
• Papadakis EN, Dokianakis DN, Spandidos DA. p53codon 72 polymorphism as a risk factor in the developmentof breast cancer. Mol Cell Biol Res Commun. 2000; 3: 389-92.
• Zhuo W, Zhang Y, Xiang Z, et al. Polymorphisms of TP53 codon 72 with breast carcinoma risk: evidence from 12226 cases and 10782 controls. J Exp Clin Cancer Res. 2009; 28: 115.
• Zhang Z, Wang M, Wu D, et al. P53 codon 72 polymorphism contributes to breast cancer risk: a metaanalysis based on 39 case-control studies. Breast Cancer Res Treat. 2010; 120: 509-17.
• Miller SA, Dykes DD, Polesky HF. A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res. 1988; 16(3): 1215.
• Storey A, Thomas M, Kalita A. et al. Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998; 393(6682): 229-34.
• Kara N, Karakus N, Ulusoy AN et al. P53 codon 72 and HER2 codon 655 polymorphisms inTurkish breast cancer patients. DNA Cell Biol. 2010; 29: 7.
• Akkiprik M, Sonmez O, Gulluoglu BM et al. Analysis of p53 gene polymorphisms and protein over-expressionin patients with breast cancer. Pathol Oncol Res. 2009; 15: 359–68.
• Ergul E, Ozel MD,Sazci A et al. TP53 Arg72Pro polymorphism in Turkish patients with sporadic amyotrophic lateral sclerosis. Neurobiol Aging. 2011; 32(11): 2107. e1-2
• Hao XD, Yang Y, Song X et al. Correlation of telomere length shortening with TP53 somatic mutations, polymorphisms and allelic loss in breast tumors and esophageal cancer. Oncol Rep. 2012; 29: 226-236.