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The purpose of this study was to clarify the roles of polymorphisms from the classical nuclear estrogen receptor ESR1 and from the recently described estrogen receptor coupled to G proteins GPR30 [1], in breast cancer susceptibility and prognosis. Three single nucleotide polymorphisms (SNPs), rs2234693 and rs9340799 from ESR1 and rs3808350 from GPR30 were genotyped in 260 breast cancer patients and 259 controls. SNPs were analyzed by PCR-RFLP and by real-time PCR with TaqMan probes. Genotypes were correlated with established breast cancer prognostic markers. For rs9340799, our results showed a significant association between A allele and breast cancer susceptibility, particularly for homozygous (OR-7.33, 95%CI, 4.3-12.6; p < 0.0005). The occurrence of polymorphisms rs2234693 and rs3808350 did not differ between breast cancer patients and controls. However, for rs2234693, CC genotype was significantly associated with higher (G2/G3) tumor grade (p < 0,05; OR-1.01, 95%CI, 1.01-4.98) and in postmenopausal women, the TT variant was associated with lower (G1) tumor grade (p = 0,02, OR-1.9, 95% CI, 1.09-3.45). No significant association was found with the presence of estrogen receptors or with HER2 overexpression in tumor samples. In conclusion, our work confirms the role of ESR1 polymorphisms in breast cancer: rs9340799 in breast cancer susceptibility and rs2234693 in breast cancer prognosis. For GPR30 SNP rs3808350, none association was found.

Polymorphisms of estrogen receptors, ERα and GPR30: association with breast cancer susceptibility and prognosis