ASPO Abstracts
Circulating Inflammatory Proteins Associated with Dementia Risk in Older Adult Cancer Survivors in the Atherosclerosis Risk in Communities (ARIC) Study
Category: Survivorship & Health Outcomes/Comparative Effectiveness Research
Conference Year: 2021
Abstract Body:
Background
Inflammation is linked to cognitive impairment(CI) in cancer survivors. But its role in survivors who develop
dementia is unclear.
Methods
We evaluated dementia risk per log2 increase in 580 inflammatory proteins in 391 dementia-free long-term (>5
yrs) older adult survivors of prostate, breast, colorectal, endometrial and bladder cancers in ARIC. Plasma
inflammatory proteins were measured at visit 5(2011-13) using SomaScan, an aptamer-based assay. Participants
were followed through visit 6(2016-17). We adjusted for age, sex, race, years since cancer diagnosis, ApoE4,
renal function, anti-inflammatory drug use and cancer/CVD shared risk factors. We also investigated proteins
associated with dementia in 196 prostate and 135 breast cancer survivors, accounting for multiple testing by
Bonferroni correction and false discovery rate Q-values.
Results
Survivors were 20% Black, 54% male, mean age of 76yrs, median time since diagnosis of 12yrs. 67 dementia
cases occurred in 1780 person-yrs. After FDR correction, 73 proteins were statistically significantly associated
with dementia risk. TMEM87B, CD9, RAF1, IL21sR and FGF7 showed the strongest positive association, with
HR:3.4-3.8 per ï„log2. LAIR1, IL36B, FGFR3, FLRT3 and LSAMP showed the strongest inverse association,
HR:0.1-0.2. Only syntaxin12 (STX12) was significant after Bonferroni correction, HR:2.2. Associations of some
inflammatory proteins with dementia were cancer site-specific. In breast cancer survivors, IL6, HMGA2, IFN-GR1,
SAP, TNFRSF1a, TNFRSF14, and TNFAIP3, were associated with dementia. STX12 and RAF1 were significantly
associated(q<0.05) with dementia in all, prostate, and breast cancer survivors.
Conclusion
Inflammatory proteins were associated with dementia in older adult cancer survivors, including STX12 (enriched in
brain, linked to WNT signaling loss, exerts CNS effects) and RAF1 (regulates MAPK/ERK pathway, previously
identified in dementia etiology). Inflammatory proteins previously associated with CI, including TNF
proteins/receptors, were associated with dementia in breast cancer survivors. If confirmed, these proteins may
warrant evaluation as potential biomarkers for dementia risk screening, and possibly preventive/therapeutic
targets in cancer survivors.
Funding:NHLBI,NCI,NPCR
Keywords: Inflammation Cancer Survivor Survivorship Dementia Proteomics