Polymorphisms of the SIPA1 gene and sporadic breast cancer susceptibility

The SNPs genotyped in this study were identified in a previous study and the genotyping assays were carried out using TaqMan SNP Genotyping Assays. The data were analysed with chi-square method and the Monte Carlo style CLUMP analysis program.Results indicated significance with SIPA1 SNP rs3741378; the CC genotype was more frequently observed in the breast cancer group compared to the disease-free control group, indicating the variant C allele was associated with increased breast cancer incidence.This observation indicates SNP rs3741378 as a novel potential sporadic breast cancer predisposition SNP. While it showed association with hormonal receptor status in breast cancer group in a previous pilot study, this exonic missense SNP (Ser (S) to Phe (F)) changes a hydrophilic residue (S) to a hydrophobic residue (F) and may significantly alter the protein functions of SIPA1 in breast tumourgenesis. SIPA1 SNPs rs931127 (5' near gene), and rs746429 (synonymous (Ala (A) to Ala (A)), did not show significant associations with breast cancer incidence, yet were associated with lymph node metastasis in the previous study. This suggests that SIPA1 may be involved in different stages of breast carcinogenesis and since this study replicates a previous study of the associated SNP, it implicates variants of the SIPA1 gene as playing a potential role in breast cancer.The novel breast cancer gene SIPA1 was originally identified as a candidate gene for breast cancer metastasis from mouse studies. Mouse Sipa1 was established as a candidate for underlying the breast cancer metastasis efficiency modifier locus Mtes 1 by Park et al [1]. The Mtes 1 loci in the mouse genome were recognized as a genetic region that substantially influenced the metastatic efficiency of mammary tumours in the mouse. The mouse Mtes 1 locus is orthologous to human chromosome 11q12-11q13, which is known to harbor the metastasis suppressor gene BRMS1. Utilizing a Multiple Cross Mapping strategy, mouse Sipa1 was id