Association of baseline inflammatory biomarkers with cancer mortality in the REGARDS cohort

Abstract

This study examines the association between inflammatory biomarkers and risk of cancer mortality by race. Data were obtained from 1,856 participants in the prospective REGARDS cohort who were cancer-free at baseline, and analyzed in relation to cancer mortality prospectively. Biomarkers were log-transformed and categorized into tertiles due to non-normal distributions, and Cox proportional hazard regression models were utilized to compute hazard ratios with 95% confidence intervals using robust sandwich methods. Individuals in the highest tertile of IL-6 had over a 12-fold increased risk of cancer mortality (HR: 12.97, 95% CI: 3.46–48.63); those in the highest tertile of IL-8 had over a 2-fold increased risk of cancer mortality (HR: 2.21, 95% CI: 0.86–5.71), while those in the highest tertile of IL-10 had over a 3-fold increased risk of cancer mortality (HR: 3.06, 95% CI: 1.35–6.89). In race-stratified analysis, each unit increase in IL-6 was associated with increased risk of cancer mortality among African-Americans (HR: 3.88, 95% CI: 1.17–12.88) and Whites (5.25, 95% CI: 1.24–22.31). If replicated in larger, racially diverse prospective cohorts, these results suggest that cancer patients may benefit from clinical or lifestyle approaches to regulate systemic inflammation as a cancer prevention strategy.

Exploring racial disparities on the association between allostatic load and cancer mortality: A retrospective cohort analysis of NHANES, 1988 through 2019

“…In the innate immune system chronic stress and associated hormones increase pro-inflammatory cytokines ( Bondar & Medzhitov, 2013 ). Long term pro-inflammation can influence all stages of cancer development through manipulation of tumor microenvironment ( Akinyemiju et al, 2019 ; Coussens & Werb, 2002 ), genetic mutation ( Lin & Karin, 2007 ), and epigenetic modifications ( Grivennikov et al, 2010 ). Crucial transcription factors like STAT3 ( Hodge et al, 2005 ) and NF-κB ( Karin & Greten, 2005 ) in precancerous cells are activated by pro-inflammatory cytokines which can lead to genetic modifications, thereby promoting tumor survival.…”

Multi-omics insights into the biological mechanisms underlying statistical gene-by-lifestyle interactions with smoking and alcohol consumption

“…Consistent with this observation, ancestry differences in smoking-related metabolites and carcinogens have been reported ( Pérez-Stable et al, 1998 ; Benowitz et al, 2011 ; Khariwala et al, 2014 ; Jain, 2015 ), and different levels of these compounds may underlie the observed differences by ancestry in genetic interactions upon smoking exposure. Additionally, there is some evidence for greater systemic oxidative stress ( Il’yasova et al, 2012 ; Morris et al, 2012 ; Annor et al, 2017 ; Kim et al, 2020 ) and inflammation ( Albert et al, 2004 ; Khera et al, 2005 ; Akinyemiju et al, 2019 ; Zahodne et al, 2019 ) among Americans of African vs. European ancestry. Exposure to cigarette smoke, a rich source of oxidants, on a background of elevated oxidative stress and inflammation may provoke a greater response among these individuals, manifesting as an interaction with smoking that differs by ancestry.…”

Multi-omics insights into the biological mechanisms underlying gene-by-lifestyle interactions with smoking and alcohol consumption detected by genome-wide trans-ancestry meta-analysis

“…Consistent with this observation, ancestry differences in smoking-related metabolites and carcinogens have been reported(37-40), and different levels of these compounds may underlie the observed differences by ancestry in genetic interactions upon smoking exposure. Additionally, there is some evidence for greater systemic oxidative stress(41-44) and, relatedly, inflammation(45-48) among Americans of African vs. European ancestry. Exposure to cigarette smoke, a rich source of oxidants, on a background of elevated oxidative stress and inflammation may provoke a greater response among these individuals, manifesting as an interaction with smoking that differs by ancestry.…”