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Cyclin D1 A870G Polymorphism in Brazilian Colorectal Cancer Patients

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Abstract

Introduction

Cyclin D1 (CCND1) is a regulatory protein involved in the cell cycle. A common G to A polymorphism in the CCND1 gene is implicated on the splicing of the CCND1 transcript, and this protein may be associated to a deregulated cell proliferation.

Aim

Correlate the polymorphism A870G of CCND1 to the risk of colorectal cancer (CRC), to environmental risk factors and clinical aspects in Brazilian patients.

Patients and Methods

One hundred twenty-three Brazilian patients with colorectal cancer were matched by age and sex to 120 healthy individuals. PCR-RFLP was performed to investigate the A870G CCND1 genotype.

Results

Between the cases 70 were men, the mean age was 62.6 years, 74.78% were stage II or III, and 91% were well or moderately differentiated. The patients were followed for a mean time of 37.22 months. The frequency of ethanol and fat intake was similar among the groups. Patients with a family history of CRC had a higher frequency of CRC compared with the controls (OR 4.16, CI 1.89–9.16). There was no difference in the frequency of the alleles A (43.8% versus 43.9%) and G (56.3% versus 56.1%) in the groups. In analysis of both control and cancer group, the influence of sex, smoking, alcohol, fiber, or meat intake did not differ significantly according to CCND1 genotype. The genotype AA or AG was associated with an increased risk of CRC (OR 3.63 CI 1.25–10.5) in patients with a family history of cancer. We did not find any association among the genotypes and localization of the tumor or prognosis. Although a difference on age onset of the tumor and genotype was not observed, patients with GG genotype had a mean 8 years lower than the others. This genotype was also associated to an increase risk of metastatic disease (OR 3.47, CI 1.38–8.68, p = 0.024).

Conclusion

We did not find a correlation among the polymorphism of CCND1 A870G and colorectal cancer risk or between this polymorphism and lifestyle habits, diet, or follow-up. GG genotype patients had an increased risk of advanced disease and between the young patients, this genotype was associated to a lower mean age. On the other hand, the genotype AA or AG had been involved to a higher risk of CRC in patients with family history of CRC.

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Acknowledgments

We thank all patients and controls who agreed to join our study. This study was financially supported by Fundaçao de Amparo a Pesquisa do Estado de Sao Paulo, State of Sao Paulo Research, Brazil.

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Authors and Affiliations

  1. Oncology Group/Gastroenterology Division, Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, Brazil

    Nora Manoukian Forones, Jacqueline Miranda de Lima, Lessileia Gomes de Souza & Ismael Dale Cotrim Guerreiro da Silva

  2. Disciplina de Gastroenterologia Clínica, Universidade Federal de Sao Paulo, R. Botucatu 740, 2º andar, São Paulo, CEP: 04023-900, Brazil

    Nora Manoukian Forones

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  1. Nora Manoukian Forones
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  2. Jacqueline Miranda de Lima
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  3. Lessileia Gomes de Souza
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Correspondence to Nora Manoukian Forones.

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Forones, N.M., de Lima, J.M., de Souza, L.G. et al. Cyclin D1 A870G Polymorphism in Brazilian Colorectal Cancer Patients. J Gastrointest Canc 39, 118–123 (2008). https://doi.org/10.1007/s12029-009-9057-z

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  • DOI: https://doi.org/10.1007/s12029-009-9057-z

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