Polymorphisms rs12998 and rs5780218 in KiSS1 suppressor metastasis gene in Mexican patients with breast cancer.

AIMS: KiSS1 is a metastasis suppressor gene associated with inhibition of cellular chemotaxis and invasion attenuating the metastasis in melanoma and breast cancer cell lines. Along the KiSS-1 gene at least 294 SNPs have been described; however the association of these polymorphisms as genetic markers for metastasis in breast cancer studies has not been investigated. Here we describe two simple PCR-RFLPs protocols to identify the rs5780218 (9DelT) and the rs12998 (E20K) KiSS1 polymorphisms and the allelic, genotypic, and haplotypic frequencies in Mexican general population (GP) and patients with benign breast disease (BBD) or breast cancer (BC). RESULTS: The rs5780218 polymorphism was individually associated with breast cancer (P = 0.0332) and the rs12998 polymorphism shows statistically significant differences when GP versus case (BC and BBD) groups were compared (P < 0.0001). The H1 Haplotype (G/-) occurred more frequently in BC group (0.4256) whereas H2 haplotype (G/T) was the most prevalent in BBD group (0.4674). CONCLUSIONS: Our data indicated that the rs5780218 polymorphism individually confers susceptibility for development of breast cancer in Mexican population and a possible role as a genetic marker in breast cancer metastasis for H1 haplotype (Wt/variant) in KiSS1 gene must be analyzed in other populations.

EcoRI polymorphism of the metastasis-suppressor gene NME1 in Mexican patients with breast cancer.

Human breast cancer cells with high metastatic potential show reduced expression of the metastasis-suppressor gene NME1. There are two polymorphic sites for the restriction enzymes BglII and EcoRI, both detectable by Southern blot analysis. Although the BglII site has been analyzed for loss of heterozygosity, the biallelic EcoRI site polymorphism has not been studied in association with breast cancer, complications or metastasis. We analyzed EcoRI site allele frequencies in Mexican patients with breast cancer, using polymerase chain reaction -restriction fragment length polymorphisms. The polymorphic allelic frequencies in the cases and reference groups were 0.4215 and 0.3375, respectively; this difference was not statistically significant (chi2=0.8687, p=0.3512). Thus, EcoR1 polymorphic site was not associated with breast cancer in this series, but could be analyzed in association with metastases and might be informative in the evaluation of loss of heterozygosity in women with breast cancer.