Oncoimmunology · 7 authors, 7 centres
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This study validates that the rs867228 loss-of-function polymorphism in the FPR1 gene accelerates the age at diagnosis of luminal B breast cancer by approximately 6.3 years in an independent French cohort. The finding suggests that incorporating this genetic marker into screening strategies could enable earlier detection in high-risk populations. The polymorphism affects about one-third of the population and may be leveraged for personalized, age-adapted breast cancer screening.
**Background:** Formyl peptide receptor-1 (FPR1) is a pathogen recognition receptor involved in cancer immunosurveillance. A single nucleotide polymorphism, rs867228, causes a loss-of-function phenotype. Previous bioinformatic analysis of The Cancer Genome Atlas (TCGA) suggested that rs867228 accelerates the age at diagnosis of luminal B breast cancer by 4.9 years. This study aimed to validate that finding in an independent cohort.
**Methods:** The study analyzed 215 patients with metastatic luminal B breast cancer from the prospective SToRM cohort (NCT01460186). Patients were genotyped for rs867228 using Illumina HumanCore Exome Chip. The primary outcome was age at first diagnosis of luminal B breast cancer, compared between carriers of at least one loss-of-function allele (TT or TG) and those with two functional alleles (GG). Statistical analysis used Mann-Whitney tests.
**Key Results:** For luminal B HER2- breast cancer, the first diagnosis occurred at an average age of 49.2 years for patients with TT or TG alleles (n=73) versus 55.6 years for GG homozygotes (n=142), a difference of 6.3 years (p=0.0067). For all luminal B breast cancers (irrespective of HER2 status), the difference was 4.2 years (51.1 vs 55.3 years, p=0.036). No significant differences were found for luminal A, HER2+, or triple-negative subtypes. The polymorphism also significantly anticipated age at metastasis by 6.35 years (p=0.038) and age at death by 5.25 years (p=0.041) in luminal B HER2- patients. However, there was no significant impact on progression-free or overall survival after diagnosis.
**Clinical Implications:** The rs867228 polymorphism accelerates luminal B breast cancer diagnosis by 5-6 years in approximately one-third of women. This finding could be incorporated into polygenic risk scores to refine personalized screening strategies, potentially increasing the frequency and stringency of examinations for high-risk individuals (e.g., those with rs867228 and diabetes or obesity). Limitations include the lack of data on other breast cancer risk genes (e.g., BRCA1/2) and the need for larger prospective studies to evaluate interactions with environmental and genetic factors.