Abstract Background: The objective of this study was to analyze the genotype distributions and allele frequencies for Threonine431Asparagine (Thr431Asn) and Arginine83Lysine (Arg83Lys) polymorphisms of the Rho kinase2 (ROCK2) gene among the breast cancer patients.Material and Methods: In this case-control study, 223 patients with breast cancer were recruited and divided into two groups according to metastases (n=128) and without metastases (n=95). Genomic DNA from the patients and the control cases (n=150) was analyzed by real-time PCR using a Light-Cycler.Results: Neither genotype distributions nor the allele frequencies for the Arg83Lys polymorphism showed a significant difference between the groups. Although no marked changes was observed with no metastasis group, a statistically significant association was found between the control and metastatic group for the Thr431Asn polymorphism of the ROCK2 gene. Further analysis revealed that there were marked associations of this polymorphism with bone, liver, and lung metastases. Homozygous carriers of the Thr431Thr genotype were more frequent among the metastatic patients (39.8%) than among controls (26.0%; P =0.0485). There was also an increase in Thr431 allele (60.5% in patients vs 51.7% in controls) and decrease in Asn431 allele frequencies (48.3% in control vs 39.5% in patients) in metastatic groups (P =0.0356). Progesterone and estrogen receptor negativity was more frequent among metastatic patients carrying a Thr431 allele when compared to the nonmetastatic group.Discussion: Our resulsts are the first to demonstrate that Thr431Asn polymorphism of the ROCK2 gene could be a risk factor for the metastases of the breast cancer, and may help in predicting the prognosis. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3038.