Association of FGFR۲ Gene Polymorphisms (rs۲۹۸۱۵۸۲ and rs۱۲۱۹۶۴۸) with Breast Cancer Susceptibility in Iranian Women: A Case-Control Study with Haplotype and Expression Analysis

Background: Breast cancer is the most common malignancy among women in Iran, characterized by a relatively early age of onset and a rising incidence rate. The single-nucleotide polymorphisms rs۲۹۸۱۵۸۲ and rs۱۲۱۹۶۴۸, located in intron ۲ of the FGFR۲ gene, have been linked to breast cancer susceptibility in genome-wide association studies (GWAS). Nevertheless, their significance in the Iranian population has not been extensively investigated.This study investigates the association of FGFR۲ polymorphisms (rs۲۹۸۱۵۸۲ and rs۱۲۱۹۶۴۸) with breast cancer risk in Iranian women, alongside haplotype interactions and gene expression profiling.Methods: A case-control study was conducted with ۱۶۰ participants (۸۰ cases and ۸۰ age-matched controls). FGFR۲ SNPs were genotyped with PCR-RFLP. Chi-square tests were used to analyze associations of haplotypes. FGFR۲ expression was evaluated in breast cancer subtypes using GEO (GDS۲۶۳۵, GDS۳۸۵۳) and Expression Atlas datasets. Statistical analyses were carried out using SPSS version ۲۲.۰ (IBM Corp., Armonk, NY, USA), with statistical significance defined as P<۰.۰۵. Hardy–Weinberg equilibrium (HWE) was verified for both SNPs in the control group (P>۰.۰۵).Results: The TT genotype of rs۲۹۸۱۵۸۲ was significantly associated with increased breast cancer risk (P=۰.۰۰; OR=۳.۵۶۶). No independent association was found for rs۱۲۱۹۶۴۸ (P>۰.۰۵). Haplotypes AC and AT were significantly associated with elevated risk (P=۰.۰۰۴ and P=۰.۰۰۱, respectively). FGFR۲ expression was upregulated in lobular carcinoma and downregulated in ductal carcinoma compared to healthy controls (P<۰.۰۵).Conclusion: The rs۲۹۸۱۵۸۲ TT genotype and specific haplotypes (AC, AT) are associated with increased breast cancer risk in Iranian women, supporting FGFR۲ as a potential biomarker for early detection and personalized risk assessment in this population.

کلیدواژه ها:

Breast cancer ، single nucleotide polymorphism ، Fibroblast growth factor receptor ۲ ، rs۲۹۸۱۵۸۲ ، rs۱۲۱۹۶۴۸