Low-grade inflammation, immune capacity, and cancer
Davidovics, Sarah A.
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Inflammation is a well-established etiological factor in carcinogenesis. The immune system may also have the capacity to identify and clear malignant cells in a process known as tumor immunosurveillance. The objective of this dissertation is to examine these roles of host immunity in carcinogenesis in immunocompetent adults. Specifically, we quantified the risk of cancer incidence and mortality by circulating, pre-diagnostic levels of the white blood cell (WBC) subtypes, neutrophils, lymphocytes, monocytes, eosinophils, and basophils, and cytomegalovirus (CMV) IgG titer in two longitudinal cohorts, the Atherosclerosis Risk in Communities (ARIC), 1987-2008, and the third National Health and Nutrition Examination Survey (NHANES III), 1988-2011. Multivariate Cox analyses were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of cancer incidence and mortality by levels of immune markers. High neutrophil count was associated with an increased risk of total (HR: 1.11, 95% CI: 1.00, 1.25) and lung (HR: 1.59, 95% CI: 1.12, 2.26) cancer incidence, and total (HR: 1.44, 95% CI: 1.22, 1.72), lung (HR: 1.66, 95% CI: 1.18, 2.33) and breast (HR: 2.09, 95% CI: 1.10, 3.97) cancer mortality. Among men, high lymphocyte count was associated with a reduced risk of cancer incidence, after excluding prostate cancer (HR: 0.75, 95% CI: 0.62, 0.91), and an increased risk of prostate cancer incidence (HR: 1.31, 95% CI: 1.03, 1.66). Among women, lymphocyte count was positively associated with cancer mortality (HR: 1.40, 95% CI: 1.07, 1.82). The presence of basophils in circulation was associated with a reduced risk of cancer incidence (HR: 0.93, 95% CI: 0.85, 1.01) and mortality (HR: 0.87, 95% CI: 0.76, 1.00). Adjustment for the other WBC subtypes did not appreciably alter these estimates. No associations were found for monocyte or eosinophil counts. Lastly, high CMV IgG antibody titer was associated with increased cancer mortality in black CMV seropositive persons (HR: 1.38, 95% CI: 1.02, 1.89), while no association was present in whites or Mexican Americans. Our findings of an association between circulating pre-diagnostic levels of neutrophils, lymphocytes, basophils, and CMV IgG and cancer incidence and mortality support a role for low-grade inflammation and subclinical immune suppression in carcinogenesis.