Amal MH Mackawy and Ola Megahed
Background: Multiple genes are known to influence the cancer metastasis but the effect of the germline heritable genetic polymorphisms on the predisposition and metastasis is not yet well known. Signal-induced proliferation associated gene1 (SIPA1) was considered as a modifying factor in the breast carcinoma (BC) metastasis process. Molecular studies on Sipa 1 gene suggested its essential role as cell adhesion regulator and metastasis modulator. The present study relied on the hypothesis that Sipa1 gene may be contributed to the risk of breast cancer occurrence and aggressiveness as well.
Objective: We aimed to examine the association of SIPA1 single nucleotide polymorphisms (SNPs) and human breast cancer incidence and prognosis in Egyptian female patients.
Patient and Methods: Two common SNPs (rs3741378 C>T and rs746429 A>G) were genotyped in 80 Egyptian females; 50 patients with breast cancer and 30 breast carcinoma free females.
Results: The rs3741378 TT genotype enhanced the incidence of breast carcinoma in comparison with the genotypes rs3741378 CC and TC (X2=7.08, P=0.029), Sipa 1 rs3741378 T allele had a high frequency in BC cases compared to controls (OR (95%)=2.593 (1.339-5.02), P=0.04). Sipa 1 rs3741378 TT genotype also displayed significant association with clinical stages, grades and lymph node metastasis (X2=12.73, P=0.013), (X2=10.88, P=0.028), (X2=6.534, P=0.010; OR (95%)=0.324 [0.134-0.781]), respectively. Pointing to those patients carrying the rs3741378 TT genotype had a higher tumor progression rate with advanced tumor grades. Oppositely, these associations could not be detected for rs746429 A>G.
Conclusion: Our results suggest that the Sipa1 promoter rs3741378 C>T SNP was contributed to BC risk and progression, which may be considered as a foretelling biomarker of BC risk and progression.
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