P Yadav1, M Masroor1, K Tanwer1, R Mir2, J Javid2, I Ahmad1, M Zuberi1, R C M Kaza3, S K Jain3, N Khurana4, P C Ray1, A Saxena5. 1. Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. 2. Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, 71491, Saudi Arabia. 3. Department of Surgery, Maulana Azad Medical College and Associated Hospitals, New Delhi, India. 4. Department of Pathology, Maulana Azad Medical College and Associated Hospitals, New Delhi, India. 5. Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, New Delhi, 110002, India. prasant.mamc@hotmail.com.
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.
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 TP53Arg72Pro and MDM2T309G polymorphisms in breast cancerpatients. 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 cancerpatients and 100 healthy control subjects. RESULTS: It was observed that TP53Arg72Pro 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 cancerpatients. 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.
Authors: A Storey; M Thomas; A Kalita; C Harwood; D Gardiol; F Mantovani; J Breuer; I M Leigh; G Matlashewski; L Banks Journal: Nature Date: 1998-05-21 Impact factor: 49.962
Authors: Nicoleta C Arva; Tamara R Gopen; Kathryn E Talbott; Latoya E Campbell; Agustin Chicas; David E White; Gareth L Bond; Arnold J Levine; Jill Bargonetti Journal: J Biol Chem Date: 2005-05-20 Impact factor: 5.157
Authors: Amy L Sherborne; Vincent Lavergne; Katharine Yu; Leah Lee; Philip R Davidson; Tali Mazor; Ivan V Smirnoff; Andrew E Horvai; Mignon Loh; Steven G DuBois; Robert E Goldsby; Joseph P Neglia; Sue Hammond; Leslie L Robison; Rosanna Wustrack; Joseph F Costello; Alice O Nakamura; Kevin M Shannon; Smita Bhatia; Jean L Nakamura Journal: Clin Cancer Res Date: 2016-09-28 Impact factor: 12.531