Circadian Misalignment and Hepatocellular Carcinoma Incidence in the United States

Abstract

Background: Circadian misalignment may increase the risk of developing hepatocellular carcinoma (HCC). The aim of this study was to examine the association between distance from time zone meridian, a proxy for circadian misalignment, and HCC risk in the United States adjusting for known HCC risk factors.Methods: Surveillance, Epidemiology, and End Results (SEER) provided information on 56,347 HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries in the United States. Distance from time zone meridian was estimated using the location of each SEER county's Center of Population in a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between distance from time zone meridian and HCC risk adjusting for individual-level age at diagnosis, sex, race/ethnicity, year of diagnosis, SEER registry, and county-level prevalence of health conditions, lifestyle factors, shift work occupation, socioeconomic status, and demographic and environmental factors.Results: A 5-degree increase in longitude moving east to west within a time zone was associated with a statistically significant increased risk for HCC (IRR, 1.07; 95% CI, 1.01-1.14, P = 0.03). A statistically significant positive association was observed among those <65 years old, while no association was observed among individuals ≥65 years old (P_{for interaction} < 0.01).Conclusions: Circadian misalignment from residing in the western region of a time zone may impact hepatocarcinogenesis.Impact: Circadian misalignment may be an independent risk factor for HCC. Cancer Epidemiol Biomarkers Prev; 27(7); 719-27. ©2018 AACR.

Figure 1

Distance from time zone meridian for the Centers of Population of 607 counties (16 SEER registries). Increasing distance from time zone meridian towards the west is shown in red, and increasing distance from time zone meridian towards the east is shown in blue. The inset map shows the time zone meridians in degrees of longitude and counties within each of the four time zones in the contiguous U.S.

Figure 2

Time zones in the U.S. and 5 degree longitude meridians. The four time zones in the contiguous U.S. are shown: Pacific, Mountain, Central, and Eastern. Meridians running north to south are shown for every 5 degrees of longitude, corresponding to the units of the incidence rate ratios presented in the study. The 607 counties included in the study are shown in cross-hatch.