The comparison between TP53 gene polymorphisms (c.[215G>C]) homozygotes and heterozygotes in Breast Cancer Patients: A clinicopathological analysis
Purpose: TP53 is a tumor suppressor gene which participates in regulation of cell cycle check points, DNA repair, and apoptosis. The aim of this study was to compare TP53 germ line gene polymorphisms (c.[215G>C]) wild – type homozygotes GG with heterozygotes GC according to clinicopathological factors.
Methods: We reviewed the medical records of 87 (22% TP53 gene homozygotes and 78% heterozygotes) breast cancer patients who were diagnosed and treated in COI in Gliwice. Polymorphism profile was assessed by RFLP-PCR technique.
Results: The presence of lobular invasive carcinoma was observed insignificantly more often in homozygotes, especially in the group of patients at the age below 50 years (29% vs. 4%, p = 0.095). Patients being TP53 gene heterozygotes had larger tumor size (T > 2) than homozygotes (16% vs. 5%, p = 0.450). There was observed a tendency to the presence of lymph node metastases (53% vs. 34%, p = 0.182) and higher Ki67 (> 20%) (69% vs. 46%, p = 0.209) in TP53 gene homozygotes. HER2 overexpression was associated with TP53 heterozygotes, especially in the group of patients at the age above 50 years (33% vs. 8%, p = 0.144). A negative receptor status was reported more frequently in homozygotes (43% vs.21%, p = 0.340) in patients with age below 50 years. Similarly higher histological grade G3 was detected more often in homozygotes in patients at the age below 50 years (80% vs. 33%, p = 0.130).
Conclusion: TP53 gene homozygotes and heterozygotes differ from each other in respect of clinicopathological factors such as: histological type, lymph node metastases, higher Ki67 (> 20%), histological grade G3, ER/PR status, tumor size (T > 2), HER2 overexpression, cancer in family history and diabetes. Patient’s age was associated with the pathological characteristics of tumor.
Wang Y, Helland A, Holm R, et al. TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival. Br J Cancer. 2004;90:678–85.
Langerød A, Zhao H, Borgan Ø, et al. TP53 mutation status and gene expression profiles are powerful prognostic markers of breast cancer. Breast Cancer Res. 2007;9(3):R30.
Chae BJ, Bae JS, Lee A, et al. p53 as a specific prognostic factor in triple-negative breast cancer. Jpn J Clin. Oncol. 2009;39(4):217–24.
Knoop AS, Bentzen SM, Nielsen MM, et al. Value of epidermal growth factor receptor, HER2, p53, and steroid receptors in predicting the efficacy of tamoxifen in high-risk postmenopausal breast cancer patients. J Clin Oncol. 2001;19:3376–84.
Campomenosi P, Monti P, Aprile A, et al. p53 mutants can often transactivate promoters containing a p21 but not Bax or PIG3 responsive elements. Oncogene. 2001; 20:3573–9.
Gasco M, Yulug IG, Crook T. TP53 mutations in familial breast cancer: Functional aspects. Hum Mutat. 2003;21(3):301-6.
Miller LD, Smeds J, George J, et al. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival. Proc Natl Acad Sci USA. 2005;102:13550–5.
Toyama T, Zhang Z, Nishio M, et al. Association of TP53 codon 72 polymorphism and the outcome of adjuvant therapy in breast cancer patients. Breast Cancer Res. 2007;9(3):R34.
Merino D, Malkin D. p53 and hereditary cancer. Subcell Biochem. 2014;85:1-16.
Qu L, He B, Pan Y, et al. Association between polymorphisms in RAPGEF1, TP53, NRF1 and type 2 diabetes in Chinese Han population. Diabetes Res Clin Pract. 2011;91(2):171-6.
Minamino T, Orimo M, Shimizu I, et al. A crucial role for adipose tissue p53 in the regulation of insulin resistance. Nat Med. 2009;15(9):1082-7.
Reiling E, Lyssenko V, Boer JMA, et al. Codon 72 polymorphism (rs1042522) of TP53 is associated with changes in diastolic blood pressure over time. Eur J Hum Genet. 2012; 20(6):696–700.
Fernández-Cuesta L, Oakman C, Falagan-Lotsch P, et al. Prognostic and predictive value of TP53 mutations in node-positive breast cancer patients treated with anthracycline- or anthracycline/taxane-based adjuvant therapy: results from the BIG 02-98 phase III trial. Breast Cancer Res. 2012;14(3):R70.
Olivier M, Langerød A, Carrieri P, et al. The clinical value of somatic TP53 gene mutations in 1,794 patients with breast cancer. Clin Cancer Res. 2006;12:1157–67.
Powell B, Soong R, Iacopetta B, et al. Prognostic significance of mutations to different structural and functional regions of the p53 gene in breast cancer. Clin Cancer Res. 2000;6:443–51.
Hamaguchi M, Nishio M, Toyama T, et al. Possible difference in frequencies of genetic polymorphisms of Estrogen Receptor a, Estrogen Metabolism and P53 Genes between Estrogen Receptor-positive and -negative breast cancers. Jpn J Clin Oncol. 2008; 38(11)734–42.
Li FP, Fraumeni JF Jr, Mulvihill JJ, et al. A cancer family syndrome in twenty-four kindreds. Cancer Res. 1988;48:5358–62.
Langerod A, Zhao H, Borgan O, et al. TP53 mutation status and gene expression profiles are powerful prognostic markers of breast cancer. Breast Cancer Res. 2007;9:R30.
Bertheau P, Lehmann-Che J, Varna M, et al. p53 in breast cancer subtypes and new insights into response to chemotherapy. Breast. 2013; 22(2):S27-9.
Melhem-Bertrandt A, Bojadzieva J, Ready KJ, et al. Early onset HER2-positive breast cancer is associated with germline TP53 mutations. Cancer. 2012; 118:908–13.
Rath MG, Masciari S, Gelman R, et al. Prevalence of germline TP53 mutations in HER2-positive breast cancer patient. Breast Cancer Res Treat. 2013;139(1):193–8.
This work is licensed under a Creative Commons Attribution 3.0 License.
International Journal of Cancer Therapy and Oncology (ISSN 2330-4049)
© International Journal of Cancer Therapy and Oncology (IJCTO)
To make sure that you can receive messages from us, please add the 'ijcto.org' domain to your e-mail 'safe list'. If you do not receive e-mail in your 'inbox', check your 'bulk mail' or 'junk mail' folders.