br The average follow up time in
The average follow-up time in the REGARDS sub-cohort was 8 years (SD = 3.3). Figs. 2 and 3 present the survival probabilities by tertiles of IL-6 and resistin, respectively. Tests of interaction between assessed bio-markers and BMI were statistically significant, p-values b0.05. Among participants with normal BMI, those in the highest vs. lowest tertile of IL-6 had a 5-fold (HR: 5.3, 95% CI: 1.6–17.8) increased risk of cancer mortality. Similar results were observed for log-transformed values of IL-6. In addition, those in the highest tertile of CRP had over a 3-fold (HR: 3.4; 95% CI: 1.0, 11.2) increased risk of cancer mortality (Table 3), while those in the highest tertile of resistin had a nearly 4-fold increased risk of cancer mortality (HR: 3.7; 95% CI: 1.2, 11.2)
Baseline characteristics of REGARDS participants by BMI category.
Normal Overweight or
a Results are mean and standard deviation (SD).
b Results are percent.
c Results are median and interquartile ranges.
Distribution of inflammatory and metabolic biomarkers among study participants.
Normal Overweight or
Abbreviation: CRP, C-reactive protein; IQR, inter quartile range; IL, interleukin; Lp(a), lipoprotein (a); SD, standard deviation. a Median (IQR).
b Results are mean and SD.
(Table 4). Among participants with overweight/obesity, highest tertile of IL-6 was associated with more than a 3-fold increased risk of cancer mortality (HR: 3.5; 95% CI: 1.5, 8.1), (Table 3). However, CRP and resistin were not significantly associated with cancer mortality in this DZNep group (Table 4).
In race-stratified analyses (Table 5), IL-6 was significantly associated with higher risk of cancer mortality among Black participants with nor-mal BMI (HR: 4.7; 95% CI: 1.3, 16.9) and overweight/obesity (HR: 3.3; 95% CI: 1.6, 7.0), and among White participants with overweight/obe-sity (HR: 3.1; 95% CI: 1.3, 7.5). Furthermore, CRP was significantly asso-ciated with an increased risk of cancer mortality, but only among White participants with normal BMI (HR: 1.9; 95% CI: 1.0, 3.4). The interaction between BMI and the exposure variables remained among Black partic-ipants (p-values b 0.05) but disappeared among White participants (p-values N 0.1), Table 5. In sensitivity analysis excluding those who died of cancer within 6 months from baseline, the associations remained con-sistent for all biomarkers evaluated (data not shown).
In prospective REGARDS cohort, after adjusting for study covariates, higher baseline IL-6, CRP, and resistin were significantly associated with increased risk of cancer mortality among participants with normal BMI, while higher IL-6 was also associated with increased risk of cancer mor-tality among participants with overweight/obesity. When stratified by race, IL-6 remained significantly associated with higher risk of cancer mortality among Blacks regardless of BMI, but only among Whites with overweight/obesity. To our knowledge, this is the first study to si-multaneously evaluate the independent associations of inflammatory and metabolic biomarkers with cancer mortality across levels of obesity.
Obesity has been well studied in relation to the risk of cancer mortal-ity; however, estimates of the risk associated with higher BMI have been inconsistent due to the limitations in the validity of BMI as a measure of adiposity, and due to differences in the type and pattern of adiposity. This has led to a renewed interest in identifying biomarkers that may be less vulnerable to measurement error and thus more reliably predict cancer risk. Recent studies have also shown that independent of obesity, metabolic health status is a key risk factor for cancer. Significant associ-ations have been observed between high blood pressure , dyslipid-emia, and type 2 diabetes [22–25] with cancer risk and mortality. Furthermore, obesity is associated with low-grade chronic inflamma-tion, which is independently associated with cancer risk [26,27]. There-fore, it is likely that obesity induces measurable changes in metabolism and inflammatory biomarkers associated with risk of cancer. It is also likely that non-obese individuals with higher levels of certain risk-associated biomarkers may be at higher risk of cancer. However, studies evaluating the impact of obesity in modifying the association between
Adiponec n Lep n
LPA Resis n
Fig. 1. Distribution of inflammatory (A) and metabolic (B) biomarkers by BMI in REGARDS BMI in kg/m2.