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Polymorphisms in cycloxygenase-2 gene and breast cancer prognosis: association between PTGS2 haplotypes and histopathological features

  • Epidemiology
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Abstract

Cyclooxygenase-2 (COX-2) overexpression is associated with worse prognosis in breast cancer. COX-2 is encoded by a polymorphic gene, called PTGS2, and its expression may be genetically influenced. In this article, we investigate the association between PTGS2 haplotypes and histopathological parameters with prognostic value on the clinical outcome of breast cancer. The study involved 606 women under current treatment for non-metastatic breast cancer. Patients were genotyped for rs689465, rs689466, rs20417, and rs5275, and their haplotypes were inferred. The distribution of PTGS2 genotypes and haplotypes was evaluated according to histopathological categorical groups used for prognostic determination of low/intermediate versus high risk of tumor recurrence. Our results indicate positive associations between variant genotypes of rs689465 and estrogen receptor negativity (OR: 1.59, 95% CI: 1.04–2.44, P: 0.02) or HER2 positivity (OR: 1.79, 95% CI: 1.00–3.18, P: 0.03), and between variant genotypes of rs20417 and estrogen receptor negativity (OR: 1.75, 95% CI: 1.15–2.57, P: 0.005), progesterone receptor negativity (OR: 1.56, 95% CI: 1.09–2.22, P: 0.01) or HER2 positivity (OR: 1.80, 95% CI: 1.04–3.13, P: 0.02). In contrast, variant genotypes of rs689466 are negatively associated with estrogen receptor negativity (OR: 0.57, 95% CI: 0.33–0.98, P: 0.03). A total of eight haplotypes were inferred, and there was a significant difference in their distribution as a function of tumor size (P: 0.011), estrogen receptor status (P: 0.018), and HER2 status (P: 0.025). PTGS2 haplotype *7 (formed by rs689465G, rs689466A, rs20417C, and rs5275T) is positively associated with higher tumor size (OR: 3.72, 95% CI: 1.19–11.22, P: 0.006), estrogen receptor negativity (OR: 2.43, 95% CI: 0.97–5.98, P: 0.032), progesterone receptor negativity (OR: 2.58, 95% CI: 1.05–6.39, P: 0.02), and HER2 positivity (OR: 4.17, 95% CI: 1.19–14.44, P: 0.007). Our results suggest that PTGS2 haplotype *7 may contribute to higher growth of untreated breast cancer and that PTGS2 haplotypes need to be considered in the characterization of breast cancer prognosis.

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Acknowledgments

This study was supported by grants from Conselho Nacional de Pesquisa e Desenvolvimento (CNPq474522/2010-5), from Fundação Carlos Chagas Filho de Amparo à Pesquisa no Rio de Janeiro (FAPERJ), and from INCT para Controle do Câncer (CNPq 573806/2008-0; FAPERJ E26/170.026/2008). JSFV, DNP, and VIB are graduate students and received a scholarship from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), LMA is an undergraduate student, with a scholarship from FAPERJ. We thank Dr. Guilherme Suarez-Kurtz for the use of laboratory facilities, and the personnel from the Breast Cancer Hospital in the Brazilian National Cancer Institute, for logistic support.

Conflict of interest

The authors declare that they have no conflicts of interest.

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Authors and Affiliations

  1. Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro—UFRJ, RJ, Brazil

    Juliana S. Festa-Vasconcellos, Diogo N. Piranda & Rosane Vianna-Jorge

  2. Divisão de Farmacologia, Coordenação de Pesquisa-Instituto Nacional do Câncer—INCA, Rua André Cavalcanti, 37, 3º Andar, RJ, 20231-050, Brazil

    Juliana S. Festa-Vasconcellos, Diogo N. Piranda, Laura M. Amaral, Vanessa Indio-do-Brasil & Rosane Vianna-Jorge

  3. Escola Nacional de Saúde Pública—FIOCRUZ, RJ, Brazil

    Vanessa Indio-do-Brasil & Sérgio Koifman

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  1. Juliana S. Festa-Vasconcellos
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  2. Diogo N. Piranda
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  3. Laura M. Amaral
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Correspondence to Rosane Vianna-Jorge.

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Festa-Vasconcellos, J.S., Piranda, D.N., Amaral, L.M. et al. Polymorphisms in cycloxygenase-2 gene and breast cancer prognosis: association between PTGS2 haplotypes and histopathological features. Breast Cancer Res Treat 132, 251–258 (2012). https://doi.org/10.1007/s10549-011-1828-0

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