ABSTRACT
BACKGROUND: Prolonged exposure to estrogens was found to be a risk factor for breast cancer. The molecular mechanism has been suggested to be the binding of estrogen receptors in mammary tissue, which promotes the proliferation of breast tissue. Different biomarkers mapping estrogen receptor alpha (ESR1) have been associated with breast cancer risk, although the size of the effect is not consistent among different reports. Variation in the estrogen receptor gene PvuII has been associated with an increased risk of developing breast cancer. However, some studies suggest that its effect might be constrained to a definite subgroup of patients. MATERIAL/METHODS: In this study the involvement of PvuII in breast cancer was analyzed in an independent sample of 444 unrelated breast cancer cases and 704 controls of Spanish origin. A case-control comparison was performed and the genotype distributions examined according to different tumor and population parameters. RESULTS: A trend towards association was observed in adjusted case-control association analysis (p=0.07). PvuII was associated with the familial forms of breast cancer (OR=3.81, p=0.02). T allele frequency was higher among patients with highly differentiated tumors (p=0.02), positive for steroid receptors (p=0.06), and negative for p53 (p=0.02). However, the PvuII genetic background did not affect disease-free survival time (p=0.65). CONCLUSIONS: The PvuII T allele may be a germline risk factor for familial forms of breast cancer and is associated with a specific subset of immunohistochemical tumor phenotype.
Subject(s)
Biomarkers, Tumor/genetics , Breast Neoplasms/genetics , Estrogen Receptor alpha/genetics , Genetic Predisposition to Disease , Alleles , Biomarkers, Tumor/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Case-Control Studies , Estrogen Receptor alpha/metabolism , Humans , Phenotype , Polymorphism, Single NucleotideABSTRACT
Nitric oxide (NO) plays a central role in the physiololgy and pathology of diverse tissues. Different studies provide data suggesting that the endothelial cell nitric oxide synthase (NOS3) expression in peritumoral microvessels might be a prognostic indicator in breast cancer patients. However, the putative contribution of common NOS3 germline variants to breast cancer risk remained unknown. A recent work comprising 269 breast cancer patients and 244 controls suggested that NOS3 Glu298Asp polymorphism is associated to breast cancer risk (OR=1.9). We performed an independent analysis of these results in 440 unrelated patients and 321 controls from Spanish population. Although our study was 90% powered to detect ORs >/=1.55, did not find any significant difference in the Glu298Asp allele distribution between cases and controls (P > 0.42). These putative reasons for this result are discussed.
