FGFR2 rs1328134: What Your Genotype Means

What each genotype means

Genomic Location and Variant Biology

The single-nucleotide polymorphism rs1328134 resides in the second intron of the FGFR2 gene on human chromosome 10. Because it is located in an intronic, non-coding region, this variant does not directly alter the amino acid sequence of the resulting receptor protein. Instead, research indicates that non-coding variations within intron 2 of FGFR2 reside in regulatory chromatin regions where transcription factors bind. Changes at these sites can alter the binding affinity of regulatory proteins, leading to subtle changes in how FGFR2 is transcribed and expressed in mammary tissue. The primary alleles identified at this locus are the cytosine (C) allele and the thymine (T) allele, or guanine (G) and adenine (A) depending on the reported genomic strand.

The Role of FGFR2 in Normal Cell Function and Cancer

The FGFR2 gene provides instructions for making fibroblast growth factor receptor 2, a member of the receptor tyrosine kinase family, as documented in MedlinePlus Genetics resources. Receptor tyrosine kinases span the cell membrane and bind specific growth factors outside the cell, triggering signaling cascades that regulate embryonic development, cell survival, differentiation, and tissue repair. Because FGFR2 plays a vital role in balancing cellular division and survival, alterations in its expression or somatic mutations within the pathway have been observed across various human malignancies, including breast, gastric, and endometrial cancers. Dysregulation of this signaling network can promote cellular proliferation in glandular breast tissue.

Scientific Research and Risk Associations

Large-scale genome-wide association studies cataloged in the GWAS Catalog have repeatedly identified single-nucleotide polymorphisms in the second intron of FGFR2 as susceptibility markers for breast cancer. The association at rs1328134 shows a preferential correlation with estrogen receptor-positive (ER+) breast cancer subtypes rather than estrogen receptor-negative subtypes. Despite being statistically robust across vast cohorts, the evidence level for rs1328134 on an individual clinical level remains categorized as limited because the effect size of each risk allele is modest—typically conferring an odds ratio of approximately 1.1 to 1.3 per allele. It is not equivalent to high-penetrance pathogenic variants in genes like BRCA1 or BRCA2.

Distribution Across Human Populations

Unlike rare familial cancer mutations, rs1328134 is a highly common variation across human populations. In European cohorts, the risk-associated allele is observed at frequencies around 40%, meaning that carrying one or two copies of this allele is normal across millions of healthy individuals. While European ancestral groups have provided the majority of large GWAS discovery datasets, research documented in global genetic catalogs indicates that allele frequencies and linkage patterns vary significantly across other ancestries, such as East Asian and African populations. Consequently, the relative statistical contribution of this specific locus may vary depending on genetic background.

Interpreting Results: What This Means for You

Finding this variant in personal genomic data cannot diagnose breast cancer, determine whether an individual will develop cancer, or provide a clinical risk score on its own. Common polygenic variants operate collectively alongside hundreds of other genomic loci, family medical history, hormonal factors, and lifestyle elements. A higher-attention genotype at rs1328134 simply reflects a slight variation in baseline genetic susceptibility seen in population studies. Anyone with personal questions about breast cancer screening, polygenic risk scoring, or familial cancer patterns should consult a licensed genetic counselor or physician rather than taking medical action based on a single intronic SNP.

Frequently asked questions

Sources & further reading

Related variants in FGFR2