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Contribution of cyclin D1 (CCND1) and E-cadherin (CDH1) alterations to colorectal cancer susceptibility: a case–control study

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Tumor Biology

Abstract

Cyclin D1 (CCND1) and E-cadherin (CDH1) are two important genes of the β-catenin/LEF pathway that is involved in tumorigenesis of various cancers including colorectal cancer (CRC). However, studies of the association between genetic variants of these two genes and CRC have shown conflicting results. We conducted a genetic association study in South Indian population (cases, 103; controls, 107) to assess the association of CCND1 870G/A and CDH1 −160C/A single nucleotide polymorphisms (SNPs) with CRC risk. Genotyping of SNPs was performed by PCR sequencing analysis. Haplotype frequencies for multiple loci and the standardized disequilibrium coefficient (D′) for pair-wise linkage disequilibrium (LD) were assessed by Haploview Software. In addition, to better understand the role of CCND1 and CDH1 in the pathophysiology of CRC, the expression pattern was evaluated in analogous tumor and adjacent normal tissues from 23 CRC patients by Western blot analysis. The frequencies of CCND1 870A/A (P = 0.045) genotype, CDH1 −160A allele (P = 0.042), and 870A/−160A haplotype (P = 0.002) were significantly higher in patients as compared with controls. Strong LD was observed between 870G/A and −160C/A SNPs in cases (D′ = 0.76) as compared to controls (D′ = 0.32). Furthermore, elevated CCND1 and diminished CDH1 expression was observed in tumor tissue as compared with analogous normal tissue of CRC patients. Interestingly, advanced-stage tumors showed wider expression alterations than in early-stage tumors. In conclusion, CCND1 870G/A and CDH1 −160C/A SNPs may modify the risk of CRC susceptibility in South Indian population. In addition, elevated CCND1 and diminished CDH1 expression appears to be useful prognostic markers for CRC.

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Acknowledgments

We deeply thank all the medical staff and study subjects involved in this study. Dr. Suresh Govatati acknowledges the financial support from the University Grants Commission, New Delhi, under its Dr. D.S. Kothari postdoctoral scheme [No.F.4-2/2006 (BSR)/13-1014/2013 (BSR)]. The authors are thankful to Dr. Nageswara Rao Tipirisetti, CDFD, Hyderabad, for fruitful discussions at all stages of the manuscript preparation.

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Authors and Affiliations

  1. Department of Biochemistry, Sri Krishnadevaraya University, Anantapur, India

    Suresh Govatati & Varadacharyulu Nallanchakravarthula

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

    Gopi Krishna Singamsetty & Kondaiah Kassetty

  3. Department of Biotechnology, Indian Institute of Technology Madras, Chennai, India

    Nayudu Nallabelli

  4. Department of Biochemistry, Krishna University Dr MRAR PG Center , Nuzvid, India

    Sravanthi Malempati

  5. Department of Advanced Research Centre, Narayana Medical College and Hospitals, Nellore, India

    Pasupuleti Sreenivasa Rao

  6. Department of Zoology, Osmania University, Hyderabad, India

    Venkata Kranthi Kumar Madamchetty & Rudramadevi Kanapuram

  7. Department of Zoology, RC College, Acharya Nagarjuna University, Repalle, India

    Sowdamani Govatati

  8. CSIR-Centre for Cellular and Molecular Biology, Hyderabad, India

    Nagesh Narayana

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

    Manjula Bhanoori

  10. Department of Zoology, GCW for Women, Acharya Nagarjuna University, Guntur, India

    Kondaiah Kassetty

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  1. Suresh Govatati
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Correspondence to Kondaiah Kassetty.

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Suresh Govatati and Gopi Krishna Singamsetty contributed equally to this work.

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Govatati, S., Singamsetty, G.K., Nallabelli, N. et al. Contribution of cyclin D1 (CCND1) and E-cadherin (CDH1) alterations to colorectal cancer susceptibility: a case–control study. Tumor Biol. 35, 12059–12067 (2014). https://doi.org/10.1007/s13277-014-2505-9

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