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Epidermal growth factor receptor gene polymorphisms are associated with prognostic features of breast cancer

Marcelo Sobral Leite12, Letícia Carlos Giacomin1, Diogo Nascimento Piranda13, Juliana Simões Festa-Vasconcellos13, Vanessa Indio-do-Brasil123, Sérgio Koifman4, Rodrigo Soares de Moura-Neto56, Marcelo Alex de Carvalho17 and Rosane Vianna-Jorge134*

Author Affiliations

1 Programa de Farmacologia, Coordenação de Pesquisa, Instituto Nacional do Câncer, Rua André Cavalcanti, 37, 3° andar CEP: 20231-050, Rio de Janeiro, RJ, Brazil

2 Department of Molecular Pathology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, Plesmanlaan 121

3 Programa de Pós-Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

4 Escola Nacional de Saúde Pública - FIOCRUZ, Rio de Janeiro, RJ, Brazil

5 Departamento de Botânica, Instituto de Biologia, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

6 Instituto Nacional de Metrologia, Qualidade e Tecnologia, Rio de Janeiro, RJ, Brazil

7 Instituto Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil

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BMC Cancer 2014, 14:190  doi:10.1186/1471-2407-14-190

Published: 14 March 2014



The epidermal growth factor receptor (EGFR) is differently expressed in breast cancer, and its presence may favor cancer progression. We hypothesized that two EGFR functional polymorphisms, a (CA)n repeat in intron 1, and a single nucleotide polymorphism, R497K, may affect EGFR expression and breast cancer clinical profile.


The study population consisted of 508 Brazilian women with unilateral breast cancer, and no distant metastases. Patients were genotyped for the (CA)n and R497K polymorphisms, and the associations between (CA)n polymorphism and EGFR transcript levels (n = 129), or between either polymorphism and histopathological features (n = 505) were evaluated. The REMARK criteria of tumor marker evaluation were followed.


(CA)n lengths ranged from 14 to 24 repeats, comprehending 11 alleles and 37 genotypes. The most frequent allele was (CA)16 (0.43; 95% CI = 0.40–0.46), which was set as the cut-off length to define the Short allele. Variant (CA)n genotypes had no significant effect in tumoral EGFR mRNA levels, but patients with two (CA)n Long alleles showed lower chances of being negative for progesterone receptor (ORadjusted = 0.42; 95% CI = 0.19–0.91). The evaluation of R497K polymorphism indicated a frequency of 0.21 (95% CI = 0.19 – 0.24) for the variant (Lys) allele. Patients with variant R497K genotypes presented lower proportion of worse lymph node status (pN2 or pN3) when compared to the reference genotype Arg/Arg (ORadjusted = 0.32; 95% CI = 0.17–0.59), which resulted in lower tumor staging (ORadjusted = 0.34; 95% CI = 0.19-0.63), and lower estimated recurrence risk (OR = 0.50; 95% CI = 0.30-0.81). The combined presence of both EGFR polymorphisms (Lys allele of R497K and Long/Long (CA)n) resulted in lower TNM status (ORadjusted = 0.22; 95% CI = 0.07-0.75) and lower ERR (OR = 0.25; 95% CI = 0.09-0.71). When tumors were stratified according to biological classification, the favorable effects of variant EGFR polymorphisms were preserved for luminal A tumors, but not for other subtypes.


The data suggest that the presence of the variant forms of EGFR polymorphisms may lead to better prognosis in breast cancer, especially in patients with luminal A tumors.

Breast cancer; EGFR; Gene polymorphisms; Gene expression; Prognostic estimates