Abstract Abstract #3094 Background: Human BCCIPalpha (Tok-1alpha) was identified as a BRCA2 and CDKN1A (p21, or p21(Waf1/Cip1)) Interacting Protein. BCCIP binds to a highly conserved domain proximate to the C-terminus of BRCA2 protein and the C-terminal domain of the CDK-inhibitor p21. Previous reports showed that BCCIP alpha enhances the inhibitory activity of p21 toward CDK2 and that BCCIP alpha inhibits the growth of certain tumor cells. In cancers harboring wild type p53, the p53 transactivation activity may be compromised by other mechanisms. It is clear from previous reports that BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 and BCCIPalpha is an important cofactor for BRCA2 in tumor suppression. In this study, specific SNPs in BCCIP, CDKN2A, BRCA2 and KLF6 (tumor suppressor gene) were screened to evaluate the potential influence of these genes in the predisposition to breast cancer.
 Materials & Methods: Blood was drawn from 204 primary breast cancer patients and 197 normal healthy subjects. An informed consent was obtained from all the study subjects. Genotyping was done using polymerase chain reaction followed by restriction enzyme digestion. SPSS version10.1 for windows software was used for data analysis.
 Results: A relatively high frequency of the mutant alleles showing significant association with breast cancer was observed when compared with age, gender and ethnic matched control subjects (KLF6- p<0.0001; BRCA2- p<0.028; CDKN2A- p<0.018). Association among these gene variables were determined using spearman correlation coefficients. Significant correlations were observed among BCCIP-BRCA2 (p< 0.003); BCCIP-CDKN2A (p< 0.004), BRCA2-CDKN2A (p<0.037) genes.
 Conclusions: Our results confirm the strong correlation of BCCIP gene with BRCA2 and CDKN2A gene. A strong association of KLF6 (tumor suppressor gene) gene with breast cancer was observed but no such correlation was identified with BCCIP, CDKN2A and/or BRCA2 suggesting that KLF6 gene may be involved in tumorigenesis using different regulating pathway. To better understand the role of these genes in the progression of breast carcinoma, gene expression studies will be performed using quantitative PCR. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3094.