Clinical Significance of TP53 (R72P) and MDM2 (T309G) Polymorphisms in Breast Cancer Patients

Overview

Journal Clin Transl Oncol

Specialty Oncology

Date 2015 Nov 11

PMID 26553387

Citations 6

Authors

P Yadav

M Masroor

K Tanwer

R Mir

J Javid

I Ahmad

M Zuberi

R C M Kaza

S K Jain

N Khurana

P C Ray

A Saxena

Affiliations

Soon will be listed here.

Abstract

Introduction: TP53 gene is the most frequently altered tumor suppressor gene in breast cancer. It has been observed that MDM2 plays a central role in regulating the TP53 pathway. This study aimed to investigate the role of TP53 Arg72Pro and MDM2 T309G polymorphisms in breast cancer patients.

Material And Method: The TP53 (Arg72Pro) and MDM2 (T309G) polymorphisms were studied in a hospital-based case control study by AS-PCR in 100 breast cancer patients and 100 healthy control subjects.

Results: It was observed that TP53 Arg72Pro polymorphism was significantly associated with breast cancer (χ (2) = 9.92, p = 0.007). A significantly increased breast cancer risk was associated with the Proline allele [odds ratio 1.84 (95 % CI: 1.22-2.77), risk ratio 1.34 (95 % CI: 1.11-1.63), p value 0.003], HER2/neu status (p = 0.01) and distant metastasis (p = 0.05). On the other hand, we have found a significant correlation between MDM2 (T309G) polymorphism with HER2/neu status (χ (2) = 11.14, p = 0.003) and distant metastasis (p value = 0.04).

Conclusion: Our finding suggests that TP53 (Arg72Pro) polymorphism may play a significant role as risk factor for breast cancer in north Indian breast cancer patients. While MDM2 (T309G) polymorphism may not be directly associated with the risk of breast cancer occurrence in the same population, but it may play role in disease progression by triggering TP53.

Citing Articles

North India Cancer Risk: A Detailed Review with Focus on Jammu and Kashmir Demographics.

Sudershan A, Bharti S, Sudershan S, Bhagat M, Bhagat S, Behlam I Asian Pac J Cancer Prev. 2024; 25(10):3489-3506.

PMID: 39471015 PMC: 11711370. DOI: 10.31557/APJCP.2024.25.10.3489.

Associations of and Polymorphisms with Early-Stage Breast Cancer.

Bartnykaite A, Savukaityte A, Ugenskiene R, Dauksaite M, Korobeinikova E, Gudaitiene J J Clin Med. 2021; 10(4).

PMID: 33669778 PMC: 7922970. DOI: 10.3390/jcm10040866.

p.Arg72Pro polymorphism of P53 and breast cancer risk: a meta-analysis of case-control studies.

Diakite B, Kassogue Y, Dolo G, Wang J, Neuschler E, Kassogue O BMC Med Genet. 2020; 21(1):206.

PMID: 33076844 PMC: 7574232. DOI: 10.1186/s12881-020-01133-8.

A case-control study on the SNP309T → G and 40-bp Del1518 of the MDM2 gene and a systematic review for MDM2 polymorphisms in the patients with breast cancer.

Jalilvand A, Yari K, Aznab M, Rahimi Z, Salahshouri Far I, Mohammadi P J Clin Lab Anal. 2020; 34(12):e23529.

PMID: 32951271 PMC: 7755803. DOI: 10.1002/jcla.23529.

Significant Association of the MDM2 T309G Polymorphism with Breast Cancer Risk in a Turkish Population.

Yilmaz M, Tas A, Donmez G, Kacan T, Silig Y Asian Pac J Cancer Prev. 2018; 19(4):1059-1062.

PMID: 29699057 PMC: 6031795. DOI: 10.22034/APJCP.2018.19.4.1059.

References

Ma H, Hu Z, Zhai X, Wang S, Wang X, Qin J . Polymorphisms in the MDM2 promoter and risk of breast cancer: a case-control analysis in a Chinese population. Cancer Lett. 2005; 240(2):261-7. DOI: 10.1016/j.canlet.2005.09.019. View

Storey A, Thomas M, Kalita A, Harwood C, Gardiol D, Mantovani F . Role of a p53 polymorphism in the development of human papillomavirus-associated cancer. Nature. 1998; 393(6682):229-34. DOI: 10.1038/30400. View

Xu Y, Yao L, Ouyang T, Li J, Wang T, Fan Z . p53 Codon 72 polymorphism predicts the pathologic response to neoadjuvant chemotherapy in patients with breast cancer. Clin Cancer Res. 2005; 11(20):7328-33. DOI: 10.1158/1078-0432.CCR-05-0507. View

Greenblatt M, BENNETT W, Hollstein M, Harris C . Mutations in the p53 tumor suppressor gene: clues to cancer etiology and molecular pathogenesis. Cancer Res. 1994; 54(18):4855-78. View

Szkandera J, Absenger G, Dandachi N, Regitnig P, Lax S, Stotz M . Analysis of functional germline polymorphisms for prediction of response to anthracycline-based neoadjuvant chemotherapy in breast cancer. Mol Genet Genomics. 2012; 287(9):755-64. DOI: 10.1007/s00438-012-0715-7. View

Petenkaya A, Bozkurt B, Akilli-Ozturk O, Kaya H, Gur-Dedeoglu B, Yulug I . Lack of association between the MDM2-SNP309 polymorphism and breast cancer risk. Anticancer Res. 2007; 26(6C):4975-7. View

Arva N, Gopen T, Talbott K, Campbell L, Chicas A, White D . A chromatin-associated and transcriptionally inactive p53-Mdm2 complex occurs in mdm2 SNP309 homozygous cells. J Biol Chem. 2005; 280(29):26776-87. DOI: 10.1074/jbc.M505203200. View

Singh V, Rastogi N, Mathur N, Singh K, Singh M . Association of polymorphism in MDM-2 and p53 genes with breast cancer risk in Indian women. Ann Epidemiol. 2007; 18(1):48-57. DOI: 10.1016/j.annepidem.2007.06.006. View

Chen J, Wu X, Lin J, Levine A . mdm-2 inhibits the G1 arrest and apoptosis functions of the p53 tumor suppressor protein. Mol Cell Biol. 1996; 16(5):2445-52. PMC: 231233. DOI: 10.1128/MCB.16.5.2445. View

10.

Surekha D, Sailaja K, Rao D, Padma T, Raghunadharao D, Vishnupriya S . Codon 72 and G13964C intron 6 polymorphisms of TP53 in relation to development and progression of breast cancer in India. Asian Pac J Cancer Prev. 2012; 12(8):1893-8. View

11.

Thomas M, Kalita A, Labrecque S, Pim D, Banks L, Matlashewski G . Two polymorphic variants of wild-type p53 differ biochemically and biologically. Mol Cell Biol. 1999; 19(2):1092-100. PMC: 116039. DOI: 10.1128/MCB.19.2.1092. View

12.

Kahlenborn C, Modugno F, Potter D, Severs W . Oral contraceptive use as a risk factor for premenopausal breast cancer: a meta-analysis. Mayo Clin Proc. 2006; 81(10):1290-302. DOI: 10.4065/81.10.1290. View

13.

Parkin D, Bray F, Ferlay J, Pisani P . Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001; 94(2):153-6. DOI: 10.1002/ijc.1440. View

14.

Boersma B, Howe T, Goodman J, Yfantis H, Lee D, Chanock S . Association of breast cancer outcome with status of p53 and MDM2 SNP309. J Natl Cancer Inst. 2006; 98(13):911-9. DOI: 10.1093/jnci/djj245. View

15.

Smith T, Miller M, Lohman K, Case L, Hu J . DNA damage and breast cancer risk. Carcinogenesis. 2003; 24(5):883-9. DOI: 10.1093/carcin/bgg037. View

16.

Dumont P, Leu J, Della Pietra 3rd A, George D, Murphy M . The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet. 2003; 33(3):357-65. DOI: 10.1038/ng1093. View

17.

Hong Y, Miao X, Zhang X, Ding F, Luo A, Guo Y . The role of P53 and MDM2 polymorphisms in the risk of esophageal squamous cell carcinoma. Cancer Res. 2005; 65(20):9582-7. DOI: 10.1158/0008-5472.CAN-05-1460. View

18.

Candeias M, Malbert-Colas L, Powell D, Daskalogianni C, Maslon M, Naski N . P53 mRNA controls p53 activity by managing Mdm2 functions. Nat Cell Biol. 2009; 10(9):1098-105. DOI: 10.1038/ncb1770. View

19.

Veronesi U, Boyle P, Goldhirsch A, Orecchia R, Viale G . Breast cancer. Lancet. 2005; 365(9472):1727-41. DOI: 10.1016/S0140-6736(05)66546-4. View

20.

Jain N, Singh V, Hedau S, Kumar S, Daga M, Dewan R . Infection of human papillomavirus type 18 and p53 codon 72 polymorphism in lung cancer patients from India. Chest. 2005; 128(6):3999-4007. DOI: 10.1378/chest.128.6.3999. View