Equipe labellisée par la Ligue contrele cancer, Université de Paris, Sorbonne Université, Paris, France.
Centre Léon Bérard, Département de Cancérologie Médicale, Lyon, France.
Oncoimmunology. 2023 Mar 21;12(1):2189823. doi: 10.1080/2162402X.2023.2189823. eCollection 2023.
Formyl peptide receptor-1 (FPR1) is a pathogen recognition receptor involved in the detection of bacteria, in the control of inflammation, as well as in cancer immunosurveillance. A single nucleotide polymorphism in , rs867228, provokes a loss-of-function phenotype. In a bioinformatic study performed on The Cancer Genome Atlas (TCGA), we observed that homo-or heterozygosity for rs867228 in (which affects approximately one-third of the population across continents) accelerates age at diagnosis of specific carcinomas including luminal B breast cancer by 4.9 years. To validate this finding, we genotyped 215 patients with metastatic luminal B mammary carcinomas from the SNPs To Risk of Metastasis (SToRM) cohort. The first diagnosis of luminal B breast cancer occurred at an age of 49.2 years for individuals bearing the dysfunctional TT or TG alleles ( = 73) and 55.5 years for patients the functional GG alleles ( = 141), meaning that rs867228 accelerated the age of diagnosis by 6.3 years (=0.0077, Mann & Whitney). These results confirm our original observation in an independent validation cohort. We speculate that it may be useful to include the detection of rs867228 in breast cancer screening campaigns for selectively increasing the frequency and stringency of examinations starting at a relatively young age.
甲酰肽受体 1(FPR1)是一种病原体识别受体,参与细菌检测、炎症控制以及癌症免疫监视。位于 中的单核苷酸多态性 rs867228 引起功能丧失表型。在对癌症基因组图谱(TCGA)进行的生物信息学研究中,我们观察到 中 rs867228 的同型或异型合子(影响大约三分之一的大陆人群)会使特定癌的诊断年龄加速 4.9 岁,包括 luminal B 乳腺癌。为了验证这一发现,我们对来自 SNPs To Risk of Metastasis(SToRM)队列的 215 名转移性 luminal B 乳腺腺癌患者进行了基因分型。携带非功能 TT 或 TG 等位基因( = 73)的个体首次诊断为 luminal B 乳腺癌的年龄为 49.2 岁,而携带功能 GG 等位基因( = 141)的患者为 55.5 岁,这意味着 rs867228 使诊断年龄提前了 6.3 岁(=0.0077,Mann & Whitney)。这些结果在独立验证队列中证实了我们的原始观察。我们推测,在乳腺癌筛查活动中检测 rs867228 可能有助于选择性地提高检查频率和严格程度,从相对年轻的年龄开始。