Effect of p53 Codon 72 Polymorphism on Clinical Outcome in Locally Advanced Breast Cancer Patients Receiving Anthracycline Based Neoadjuvant Chemotherapy

    Published on:January 2017
    Journal of Young Pharmacists, 2017; 9(1):114-119
    Original Article | doi:10.5530/jyp.2017.9.21
    Authors:

    Sambasivam Gopinath*1 , Deepak Gopal Shewade1, Biswajit Dubashi2, Dharanipragada Kadambari3, Ananthakrishnan Ramesh4, Ramasamy Kesavan1

    1Department of Pharmacology, JIPMER, Puducherry, INDIA.

    2Department of Medical oncology, JIPMER, Puducherry, INDIA.

    3Department of Surgery, JIPMER, Puducherry, INDIA.

    4Department of Radio Diagnosis, JIPMER, Puducherry, INDIA.

    Abstract:

    Background: Breast cancer is the second most common cancer in the world after lung cancer and the most common cancer among women. Most of the women exhibit interindividual variation to cytotoxic therapy. It may be due to the genetic polymorphism of genes involved in pharmacokinetics and pharmacodynamics pathways of drugs. Various studies implicated the role of p53 gene polymorphism in the sensitivity of apoptosis. Objective: The objective of the study was to know the effect of p53 tumor suppressor gene 72 codon polymorphism on response in breast cancer patients receiving anthracycline-based neoadjuvant chemotherapy. Results: A total of 170 patients were enrolled for the study. The median age of the patient group was 50 year (23-60). The majority of patients were post-menopausal (61%). Most of the patients were node positive and also found to have grade II tumor. Hormone receptor positivity of estrogen, progesterone, and human epidermal growth factor were 48%, 37%, and 60%. The genotype of 72 G>C codon polymorphism was done by real time-polymerase chain reaction The frequencies of wild homozygous variant GG, heterozygous variant GC, and mutant homozygous variant CC were found to be 42%, 43%, and 15% respectively. 145 patients were assessed for response of which 133 patients were found be responders and 12 patients were found be non-responders. The genotype frequency of P5379G>A variant were significantly different between patients having a complete and partial response in the recessive genetic model (RR=0.2972, C.I=0.078-1.122, P=0.03.). However there was no association of genotypes with progression-free survival and overall survival. Conclusion: This study concludes that p53 gene polymorphism partially may have a role in predicting the response in breast cancer patients.

    Key words: p53 tumor suppressor gene, Single nucleotide polymorphism, Anthracyclines, Tumor response, Pathological response.

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