Explaining the link between adiposity and colorectal cancer risk in men and postmenopausal women in the UK Biobank: a sequential causal mediation analysis
Menée au Royaume-Uni à partir de données 2006-2010 portant sur 229 134 hommes et 273 402 femmes (âge : 40-69 ans ; durée moyenne de suivi : 7,1 ans), cette étude analyse le rôle de la protéine C-réactive, de l'hémoglobine glyquée, de la globuline de liaison aux hormones sexuelles et de la testostérone dans l'association entre l'obésité et le risque de cancer colorectal (2 070 cas : 1 280 hommes, 790 femmes ménopausées)
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 vs 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. This article is protected by copyright. All rights reserved.