Patients with autoimmune disorders (AD) have altered cancer risks compared to the general population. Systemic lupus erythematosus and multiple sclerosis lead to a heightened risk for hematological malignancies and decreased risk for breast, ovarian, and prostate malignancies. Often patients with autoimmune disease have dysregulated antiviral immune responses, including against oncogenic viruses. To uncover the relationship between viral incidence and cancer risk in the context of autoimmune disease, we extracted electronic health records (EHR) from Vanderbilt University. ICD-9/10 codes and laboratory values were collected for hematological, lung, anal-vaginal, thyroid, hepatobiliary, bladder, prostate, and breast cancers; and viruses including Epstein Barr virus (EBV), Human papilloma virus (HPV), and Hepatitis A/B/C (Hep). Only viral infections that led to a physician visit or laboratory test were entered into the EMR; therefore, only clinically relevant cases were noted and considered positive in this study. The relationship between virus infection and cancer in an SLE cohort (SLE-cases n = 2,313, and SLE-controls n = 5,702) and an MS cohort (MS-case n = 7,277, MS-control n = 7,277) was examined by multilinear logistic regression. Viral infection was strongly associated with increased risk for cancer overall. SLE and MS patients were more susceptible to all viral infections. MS patients trended toward increased risk for cancers overall, while decreased risk for hormone-based cancers in SLE patients non-significantly reduced their risk for overall cancer. Both SLE and MS patients had increased clinically relevant EBV infection, which was associated with risk for hematological cancers. Preventing viral infections by vaccination may be especially helpful in controlling risk for cancer in SLE and MS patients.
Background Metabolic pathways are related to physiological functions and disease states and are influenced by genetic variation and environmental factors. Hispanics/Latino individuals have ancestry-derived genomic regions (local ancestry) from their recent admixture that have been less characterized for associations with metabolite abundance and disease risk. Methods We performed admixture mapping of 640 circulating metabolites in 3887 Hispanic/Latino individuals from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Metabolites were quantified in fasting serum through non-targeted mass spectrometry (MS) analysis using ultra-performance liquid chromatography-MS/MS. Replication was performed in 1856 nonoverlapping HCHS/SOL participants with metabolomic data. Results By leveraging local ancestry, this study identified significant ancestry-enriched associations for 78 circulating metabolites at 484 independent regions, including 116 novel metabolite-genomic region associations that replicated in an independent sample. Among the main findings, we identified Native American enriched genomic regions at chromosomes 11 and 15, mapping to FADS1/FADS2 and LIPC, respectively, associated with reduced long-chain polyunsaturated fatty acid metabolites implicated in metabolic and inflammatory pathways. An African-derived genomic region at chromosome 2 was associated with N-acetylated amino acid metabolites. This region, mapped to ALMS1, is associated with chronic kidney disease, a disease that disproportionately burdens individuals of African descent. Conclusions Our findings provide important insights into differences in metabolite quantities related to ancestry in admixed populations including metabolites related to regulation of lipid polyunsaturated fatty acids and N-acetylated amino acids, which may have implications for common diseases in populations.
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