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  • Oncogenomics
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Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer

Oncogene volume 21, pages 1928–1933 (2002)Cite this article

Abstract

The molecular basis for most non-HNPCC familial colorectal cancer cases is unknown, but there is increasing evidence that common genetic variants may play a role. We investigated the contribution of polymorphisms in two genes implicated in the pathogenesis of colorectal cancer, cyclin D1 (CCND1) and E-cadherin (CDH1), to familial and sporadic forms of the disease. The CCND1 870A/G polymorphism is thought to affect the expression of CCND1 through mRNA splicing and has been reported to modify the penetrance of HNPCC. Inactivation of E-cadherin is common in colorectal cancer, and truncating germline mutations have been reported to confer susceptibility to colorectal as well as diffuse gastric cancer. The −160A/C CDH1 polymorphism appears to affect expression of CDH1 and may therefore also confer an increased risk. We found a significantly higher frequency of CCND1 870A allele in 206 familial cases compared to 171 controls (P=0.03). Odds ratios in heterozygotes and homozygotes were 1.7 (95% CI: 1.0–2.66) and 1.8 (95% CI: 1.0–3.3) respectively. The difference was accounted for by an over-representation of A allele in non-HNPCC familial cases (P=0.007). Over-representation of the CCND1 A allele was also seen in sporadic colorectal cancer cases compared to controls but this did not attain statistical significance (P=0.08). No significant differences between the frequency of CDH1 −160A/C genotypes in familial, sporadic colorectal cancer cases and controls were seen, although a possible association between the low expressing A allele and right-sided tumours was detected in familial cases.

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Acknowledgements

We thank the many patients, clinicians and scientists who contributed to this study. We are grateful to the Birmingham United Hospitals Endowment Fund (TR Porter, FM Richards, ER Maher, JA Jankowski) and The Wellcome Trust (JA Jankowski) for financial support.

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Authors and Affiliations

  1. Department of Paediatrics and Child Health, Section of Medical and Molecular Genetics, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Timothy R Porter, Frances M Richards & Eamonn R Maher

  2. Section of Cancer Genetics, Institute of Cancer Research, 15, Cotswold Road, Sutton, Surrey, SM2 5NG, UK

    Richard S Houlston

  3. Department of Medical Genetics, St. Mary's Hospital, Manchester

    D Gareth R Evans

  4. UK

    D Gareth R Evans

  5. Department of Medicine, University of Birmingham, Edgbaston, Birmingham, B15 2TH, UK

    Janusz A Jankowski

  6. West Midlands Regional Genetics Service, Birmingham Women's Hospital, Edgbaston, Birmingham, B15 2TG, UK

    Fiona Macdonald

  7. Oxford Regional Genetics Service, Churchill Hospital, Oxford, OX3 7LJ, UK

    Gail Norbury & Ian Tomlinson

  8. North West Thames Genetics Service, Kennedy-Galton Centre, Northwick Park Hospital, Harrow, UK

    Stewart J Payne & Samantha A Fisher

  9. Molecular and Population Genetics Laboratory, Imperial Cancer Research Fund, 44, Lincoln's Inn Fields, London, WC2A 3PX, UK

    Ian Tomlinson

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  1. Timothy R Porter
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  2. Frances M Richards
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Correspondence to Eamonn R Maher.

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Porter, T., Richards, F., Houlston, R. et al. Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer. Oncogene 21, 1928–1933 (2002). https://doi.org/10.1038/sj.onc.1205245

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