The interaction between systemic inflammatory markers and polygenic risk score in breast cancer risk: A cohort study in the UK Biobank

• Published in: Cancer epidemiology 2023-12, Vol.87, p.102490-102490, Article 102490
• Main Authors: Yang, Zixuan, Zhang, Yanyu, Song, Mengjie, Huang, Xiaoxi, Lin, Yuxiang, Yang, Haomin
• Format: Article
• Language: English
• Subjects: Biobanks; Biological Specimen Banks; Biomarkers, Tumor - genetics; Breast cancer; Breast Neoplasms - diagnosis; Breast Neoplasms - epidemiology; Breast Neoplasms - genetics; C-Reactive Protein; Cohort analysis; Cohort Studies; Confidence intervals; Female; Genetics; Health risks; Hormone replacement therapy; Humans; Inflammation; Inflammatory biomarkers; Interaction; Leukocytes (neutrophilic); Likelihood ratio; Lymphocytes; Medical prognosis; Mortality; Neutrophils; Regression analysis; Risk Factors; Sensitivity analysis; United Kingdom - epidemiology; Womens health
• ISSN: 1877-7821; 1877-783X
• DOI: 10.1016/j.canep.2023.102490

Systemic inflammatory markers have been widely used in cancer prognosis prediction recently. However, there is limited knowledge regarding their impact on breast cancer risk and their interaction with polygenic risk scores. A cohort study of 202,403 female participants from the UK Biobank were analyzed to estimate the hazard ratio (HR) for the incidence and mortality of breast cancer based on inflammatory markers using Cox regression models. Additionally, we stratified the analysis by polygenic risk scores (PRS) for breast cancer, and examined the interaction between these markers and PRS through likelihood ratio tests and relative excess risk due to interaction (RERI). Women in the highest tertile of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), and C-reactive protein (CRP) showed an increased risk of breast cancer [HR (95 %CI) = 1.10 (1.02–1.18), 1.09 (1.01–1.17) and 1.15 (1.05–1.25), respectively], as compared to those in the lowest tertile. Regarding breast cancer mortality, only NLR and CRP exhibited consistent results in the univariate model [HR (95 %CI) = 1.25 (0.99–1.58) and 1.39 (1.10–1.77), respectively]. When stratified by PRS, stronger associations between inflammatory markers and breast cancer risk were observed in the high PRS group. Furthermore, there was a significant additive interaction between CRP and PRS [RERI (95 % CI) = 0.30 (0.06–0.53)]. NLR and CRP are associated with breast cancer risk and mortality, and the effect of CRP is influenced by PRS. Systematic inflammatory markers, together with PRS, might be applied in combined screening for breast cancer. •Women with the highest tertile of NLR, SII and CRP had an increased risk of breast cancer.•NLR and CRP were also associated with breast cancer mortality, consisting with their effect on breast cancer incidence.•CRP was associated with breast cancer only in the high genetic risk group, suggesting an additive interaction.