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TP53 alterations and colorectal cancer predisposition in south Indian population: A case-control study

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Tumor Biology

Abstract

The objective of the present study was to investigate the association between TP53 gene single nucleotide polymorphisms (SNPs) and colorectal cancer (CRC) predisposition in south Indian population and to evaluate the role of TP53 expression in the pathophysiology of CRC. A genetic association study was conducted in 103 CRC cases and 107 controls of south Indian origin. We genotyped ten selected TP53 SNPs by polymerase chain reaction-sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D′) for pairwise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand the role of TP53 in the pathophysiology of CRC, the expression pattern was evaluated in analogous tumor and normal tissues from 23 CRC patients by Western blot analysis. The frequencies of Pro72Pro (P = 0.0033) genotype and Ser47/Pro72 (P = 0.00171) haplotype were significantly higher in patients as compared to controls. Strong LD was observed between codon 47 and 72 in cases (D′ = 0.32) as compared to controls (D′ = 0.21). The polymorphism was not observe at the remaining eight SNPs loci analyzed. Furthermore, increased TP53 expression was observed in tumor tissue than in analogous normal tissue of CRC patients. Interestingly, advanced stage tumors showed more elevated TP53 expression compared to early stage tumors. In conclusion, the TP53 Pro72Pro genotype and Ser47/Pro72 haplotype has an increased risk for CRC predisposition in south Indian population. In addition, elevated TP53 expression appears to be useful prognostic marker for CRC.

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Acknowledgments

We deeply thank all the medical staff and study subjects involved in this study.

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Authors and Affiliations

  1. Department of Zoology, Acharya Nagarjuna University, Guntur, India

    Gopi Krishna Singamsetty, Anil Kumar kuraganti & Kondaiah Kassetty

  2. Department of Biochemistry, Krishna University, Nuzvid, India

    Sravanthi Malempati

  3. Department of Biotechnology, Montessori Mahila Kalasala, Acharya Nagarjuna University, Vijayawada, India

    Srichandana Bhogadhi

  4. Centre for Cellular and Molecular Biology (CCMB), Hyderabad, India

    Ravinder Kondreddy & Naveen Kumar Tangudu

  5. Department of Biochemistry, Osmania University, Hyderabad, India

    Suresh Govatati & Manjula Bhanoori

  6. Department of Zoology, RC College, Acharya Nagarjuna University, Guntur, India

    Sowdamani Govatati

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  1. Gopi Krishna Singamsetty
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  2. Sravanthi Malempati
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Correspondence to Kondaiah Kassetty.

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Gopi Krishna Singamsetty and Sravanthi Malempati contributed equally to this work.

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Singamsetty, G.K., Malempati, S., Bhogadhi, S. et al. TP53 alterations and colorectal cancer predisposition in south Indian population: A case-control study. Tumor Biol. 35, 2303–2311 (2014). https://doi.org/10.1007/s13277-013-1305-y

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