Geographic variation in the incidence of marginal zone lymphoma (MZL) subtypes and infectious risk factors.

Abstract

e13094 Background: Helicobacter pylori is a known etiologic factor for gastric MZL, but data for infectious etiology in other MZL subtypes are controversial. Proposed hypothetical factors include Borrelia burgdorferi for cutaneous MZL (cMZL), Campylobacter (Cmp) for intestinal MZL (iMZL), and hepatitis C (HCV) for splenic (SMZL) or nodal MZL (NMZL). We explored geographic variation in the incidence rate (IR) of MZL and reportable infections in the United States (US) to examine these hypotheses. Methods: Using the National Program of Cancer Registries, we calculated age-adjusted IR (per 100 000 person-years) of MZL subtypes for each US state in 2001-2015. We linked them to the 2010 US census data, data on IR (per 10 000) of Lyme disease (2001-2015) and Cmp infections (2016) from the Center for Disease Control, and to published estimates of HCV prevalence (2013-2016). We examined the hypotheses in multivariable Poisson models adjusting for median age, proportion of men, Black or Asian individuals in each state, reporting adjusted IR ratios (IRR) with 95% confidence intervals (CI). Results: The study included 5,085 cases of cMZL, 3,948 of iMZL, 26,648 of NMZL, and 12,184 of SMZL. Across the US, IR varied between 0.02 and 0.22 for cMZL, 0.04-0.12 for iMZL, 0.33-0.91 for NMZL, and 0.12-0.47 for SMZL. For all subtypes, IR was highest in the Northeast, and lowest in the South ( P<.0001), consistent with general lymphoma epidemiology. However, the IRR for South relative to Northeast was significantly lower for cMZL (0.42; CI, 0.38-0.45) than iMZL (0.65), NMZL (0.65), SMZL (0.67), or aggregate MZL (0.65; CI, 0.64-0.66). In adjusted models, IR of Lyme disease was significantly associated with increased IR of cMZL (IRR=1.11; CI, 1.07-1.16), and Cmp infection was associated with iMZL (IRR=1.19; CI, 1.02-1.38). In contrast, HCV, prevalent in the South, was inversely associated with all MZL subtypes. Conclusions: These results support the putative association between cMZL and Lyme disease, and between iMZL and Cmp infection. Conversely, lack of positive association between any MZL subtype and HCV suggests that it is not a major pathogenic factor in the US. These ecological results do not rule out associations at the individual level, which will require further research.