Personalized and Precision Medicine Journal
Where Innovations Meets Personalized and Precision Medicine

Association of FGFR2 Gene Polymorphisms (rs2981582 and rs1219648) with Breast Cancer Susceptibility in Iranian Women: A Case-Control Study with Haplotype and Expression Analysis

Document Type : Original Article

Authors

Sahar Adl 1
Ahmad Hamta 2

1 Department of Biology, Faculty of Basic Sciences, Arak University, Arak, Iran

2 Department of Biology, Faculty of Basic Sciences, Arak University, Arak, Iran.

https://doi.org/10.22034/ppmj.2026.735666
Abstract
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 rs2981582 and rs1219648, located in intron 2 of the FGFR2 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 FGFR2 polymorphisms (rs2981582 and rs1219648) with breast cancer risk in Iranian women, alongside haplotype interactions and gene expression profiling.
Methods: A case-control study was conducted with 160 participants (80 cases and 80 age-matched controls). FGFR2 SNPs were genotyped with PCR-RFLP. Chi-square tests were used to analyze associations of haplotypes. FGFR2 expression was evaluated in breast cancer subtypes using GEO (GDS2635, GDS3853) and Expression Atlas datasets. Statistical analyses were carried out using SPSS version 22.0 (IBM Corp., Armonk, NY, USA), with statistical significance defined as P<0.05. Hardy–Weinberg equilibrium (HWE) was verified for both SNPs in the control group (P>0.05).
Results: The TT genotype of rs2981582 was significantly associated with increased breast cancer risk (P=0.00; OR=3.566). No independent association was found for rs1219648 (P>0.05). Haplotypes AC and AT were significantly associated with elevated risk (P=0.004 and P=0.001, respectively). FGFR2 expression was upregulated in lobular carcinoma and downregulated in ductal carcinoma compared to healthy controls (P<0.05).
Conclusion: The rs2981582 TT genotype and specific haplotypes (AC, AT) are associated with increased breast cancer risk in Iranian women, supporting FGFR2 as a potential biomarker for early detection and personalized risk assessment in this population.

Keywords

Breast cancer
Single nucleotide polymorphism
Fibroblast growth factor receptor 2
rs2981582
rs1219648
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Personalized and Precision Medicine Journal
Volume 11, Issue 40 - Serial Number 40
Original article
Winter 2026
Pages 1-7

  • Receive Date 15 November 2025
  • Revise Date 23 February 2025
  • Accept Date 08 March 2026

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