A polymorphism in the G protein beta3-subunit gene is associated with bone metastasis risk in breast cancer patients

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 pathway...

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Bibliographic Details
Published in:Breast cancer research and treatment 2008-10, Vol.111 (3), p.449-452
Main Authors: Clar, H, Langsenlehner, U, Krippl, P, Renner, W, Leithner, A, Gruber, G, Hofmann, G, Yazdani-Biuki, B, Langsenlehner, T, Windhager, R
Format: Article
Language:English
Subjects:
Adult
Aged
Bone Neoplasms - genetics
Bone Neoplasms - prevention & control
Bone Neoplasms - secondary
Breast Neoplasms - genetics
Breast Neoplasms - pathology
Female
Gene Expression Regulation, Neoplastic
Gene Frequency
Genetic Predisposition to Disease
Heterotrimeric GTP-Binding Proteins - genetics
Humans
Middle Aged
Neoplasm Staging
Polymorphism, Genetic
Proportional Hazards Models
Retrospective Studies
Risk Assessment
Risk Factors
Time Factors
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Summary: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% CI 0.08-0.61; P = 0.004) for bone metastasis. We conclude that the homozygous GNB3 825 TT genotype may be protective against development of bone metastasis in breast cancer patients. The precise mechanism for this remains to be determined, but could be due to a direct involvement of G protein-coupled receptors in bone metabolism.
ISSN:0167-6806