Polymorphisms rs12998 and rs5780218 inKiSS1Suppressor Metastasis Gene in Mexican Patients with Breast Cancer

Abstract

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.

Single nucleotide variants in metastasis‐related genes are associated with breast cancer risk, by lymph node involvement and estrogen receptor status, in women with European and African ancestry

“…One SNP we examined, rs3795573, was predicted to affect binding (RegulomeDB score 2b). One prior study found that rs5780218 was significantly associated with risk of breast cancer among Mexican patients , but this SNP is not in LD with any of the ones we included.…”

Evaluation of the correlation of MACC1, CD44, Twist1, and KiSS-1 in the metastasis and prognosis for colon carcinoma

“…KiSS-1 is considered a metastatic suppressor in many cancers [ 11 , 25 , 26 ]. Results have demonstrated that the normal expression of KiSS-1 can suppress tumor cell growth, motility, and migration.…”

“…The KiSS-1 gene, which encodes a 145-amino-acid protein, can bind to the G protein-coupled receptor 54 (GPR54, also called KiSS-1R). KiSS-1 can control cell-cell adhesion by promoting E-cadherin expression and cell-matrix adhesion and cytoskeleton remodeling through inhibition of MMP expression [ 11 , 24 , 25 ]. KiSS-1 expression is also reported to suppress the metastatic potential of tumor cells but not tumorigenicity [ 25 , 26 ].…”

“…KiSS-1 can control cell-cell adhesion by promoting E-cadherin expression and cell-matrix adhesion and cytoskeleton remodeling through inhibition of MMP expression [ 11 , 24 , 25 ]. KiSS-1 expression is also reported to suppress the metastatic potential of tumor cells but not tumorigenicity [ 25 , 26 ]. Further studies have demonstrated that downregulation of KiSS-1 may be involved in the process of tumor invasiveness and metastasis [ 11 , 25 , 26 ].…”

“…KiSS-1 expression is also reported to suppress the metastatic potential of tumor cells but not tumorigenicity [ 25 , 26 ]. Further studies have demonstrated that downregulation of KiSS-1 may be involved in the process of tumor invasiveness and metastasis [ 11 , 25 , 26 ].…”