Review of FSCN1 polymorphism and susceptibility to breast cancer in Egyptian and Chinese patients

Breast cancer is a major cause of cancer-related morbidity and mortality in women worldwide. Beyond high-penetrance susceptibility genes, common genetic variants with modest effects may also influence breast cancer risk. Fascin-1, encoded by FSCN1, is an actin-bundling protein that regulates cytoskeletal remodelling, cell motility, and metastasis, and its overexpression has been linked to aggressive breast cancer phenotypes. However, the role of FSCN1 germline polymorphisms in breast cancer susceptibility remains insufficiently defined. This systematic review aimed to critically appraise and synthesise existing evidence on the association between FSCN1 single-nucleotide polymorphisms (SNPs) and breast cancer risk. A comprehensive literature search of PubMed, Embase, Web of Science, and the Cochrane Library was conducted up to December 31, 2025. Eligible studies were case-control designs evaluating associations between FSCN1 polymorphisms and breast cancer, with sufficient genotype or allele frequency data. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Given heterogeneity in populations and investigated SNPs, a qualitative synthesis was performed. Four case-control studies involving Chinese and Egyptian populations met the inclusion criteria. Sample sizes ranged from 96 to 316 cases and 50 to 222 controls. All studies employed PCR-TaqMan genotyping and demonstrated Hardy-Weinberg equilibrium in control groups. Associations between FSCN1 polymorphisms and breast cancer risk varied by SNP and population. The rs56156320 AC genotype was associated with increased risk in a Chinese case-control study, whereas the rs3801004 and rs852479 variants showed protective associations in Egyptian populations. Other polymorphisms exhibited inconsistent or non-significant associations. Overall study quality was moderate to high, but effect estimates were heterogeneous. Current evidence suggests that FSCN1 polymorphisms may influence breast cancer susceptibility in an allele-specific and population-dependent manner. Larger, multi-ethnic studies incorporating functional genomics are needed to clarify their role in breast cancer risk stratification.