2784

GNB3

guanine nucleotide binding protein (G protein), beta polypeptide 3;GNB3;guanine nucleotide binding protein (G protein), beta polypeptide 3

G protein, beta-3 subunit|GTP-binding regulatory protein beta-3 chain|guanine nucleotide-binding protein G(I)/G(S)/G(T) beta subunit 3|guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3|hypertension associated protein|transducin beta chain 3

12p13

protein-coding

The 825C>T polymorphism in the gene for the G-protein beta3 subunit (GNB3) has been linked to the occurrence of a splice variant of GNB3 and distinct cellular and metabolic features and may be associated with malignant disease. 500 patients with histologically confirmed breast cancer and 500 female age-matched healthy control subjects were genotyped for the GNB3 polymorphism to analyze its role for breast cancer. Prevalences of GNB3 CC, CT and TT genotypes were similar among patients (49.7, 39.8, 10.5%) and controls (50.1, 42.4, 7.5%, P = 0.25). The GNB3 genotype was furthermore not linked to tumor size, histological grading, estrogen or progesterone receptor status and age at diagnosis. In an exploratory analysis, carriage of a 825-T allele was associated with a longer metastasis-free period in patients with primary low-grade breast cancer, but not in those with primary high-grade breast cancer (Cox regression, P = 0.025). We conclude that the GNB3 825C>T polymorphism does not appear to be associated with breast cancer risk, but may influence development of metastasis in low-grade tumors.

Breast cancer is the most frequently diagnosed cancer among women in western countries and bone metastases of breast cancer cause significant morbidity. G proteins are important components of a multitude of transmembrane receptors and are involved in the regulation of intracellular signaling pathways such as parathormone receptors 1 and 2 (PTH1 and 2), extracellular calcium-sensing receptor, the calcitonin receptor and the OPG/RANKL-system. A common polymorphism in the gene encoding the G protein beta3-subunit, GNB3 825C > T, has been linked to increased G protein activation. To analyse the role of this polymorphism in bone metastasis of breast cancer, we determined GNB3 825C > T genotypes in 500 female breast cancer patients. According to breast cancer staging, patients were divided in three groups, representing patients without metastases (n = 250), those with metastases other than bone (n = 117), and those with bone metastasis (n = 133). Frequency of the GNB3 825 TT genotype was significantly lower among patients with bone metastases (3.1%) than among those with other metastases (12.8%; P = 0.004) or no metastases (13.3%; P < 0.001). In a Cox regression analysis, relative risk of the GNB3 TT genotype for bone metastasis was 0.22 (95%