Work

Explaining the link between adiposity and colorectal cancer risk in men and postmenopausal women in the UK Biobank: A sequential causal mediation analysis

Year: 2020

Type: article

Abstract: Mechanisms underlying adiposity–colorectal cancer (CRC) association are incompletely understood. Using UK Biobank data, we investigated the role of C‐reactive protein (CRP), hemoglobin‐A1c (HbA1c) and (jointly) sex hormone‐binding globulin (SHBG) and testosterone, in explaining this association. Total effect of obesity versus normal‐weight (based on waist circumference, body mass index, waist–hip ratio) on CRC risk was decomposed into natural direct (NDE) and indirect (NIE) effects using sequential mediation analysis. After a median follow‐up of 7.1 years, 2070 incident CRC cases (men = 1,280; postmenopausal women = 790) were recorded. For men, the adjusted risk ratio (RR) for waist circumference (≥102 vs. ≤94 cm) was 1.37 (95% confidence interval [CI], 1.19–1.58). The RRsNIE were 1.08 (95% CI: 1.01–1.16) through all biomarkers, 1.06 (95% CI: 1.01–1.11) through pathways influenced by CRP, 0.99 (95% CI: 0.97–1.01) through HbA1c beyond (the potential influence of) CRP and 1.03 (95% CI: 0.99–1.08) through SHBG and testosterone combined beyond CRP and HbA1c. The RRNDE was 1.26 (95% CI: 1.09–1.47). For women, the RR for waist circumference (≥88 vs. ≤80 cm) was 1.27 (95% CI: 1.07–1.50). The RRsNIE were 1.08 (95% CI: 0.94–1.22) through all biomarkers, 1.08 (95% CI: 0.99–1.17) through CRP, 1.00 (95% CI: 0.98–1.02) through HbA1c beyond CRP and 1.00 (95% CI: 0.92–1.09) through SHBG and testosterone combined beyond CRP and HbA1c. The RRNDE was 1.18 (95% CI: 0.96–1.45). For men and women, pathways influenced by CRP explained a small proportion of the adiposity‐CRC association. Testosterone and SHBG also explained a small proportion of this association in men. These results suggest that pathways marked by these obesity‐related factors may not explain a large proportion of the adiposity‐CRC association.

Source: International Journal of Cancer

DOI: 10.1002/ijc.32980