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. 2020 Oct 1;147(7):1881-1894.
doi: 10.1002/ijc.32980. Epub 2020 Apr 13.

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

S Ghazaleh Dashti  1   2 , Vivian Viallon  2 , Julie A Simpson  1 , Amalia Karahalios  1   3 , Margarita Moreno-Betancur  4   5 , Dallas R English  1   6 , Marc J Gunter  2 , Neil Murphy  2
Affiliations

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

S Ghazaleh Dashti et al. Int J Cancer. .

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.

Keywords: C-reactive protein; adiposity; causal mediation analysis; colorectal cancer; hemoglobin-A1c; inflammation; insulin resistance; sex-hormone-binding globulin; sex-steroid hormones; testosterone.

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References

    1. Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.
    1. Arnold M, Sierra MS, Laversanne M, et al. Global patterns and trends in colorectal cancer incidence and mortality. Gut 2017;66:683-91.
    1. Lauby-Secretan B, Scoccianti C, Loomis D, et al. Body fatness and cancer-viewpoint of the IARC working group. N Engl J Med 2016;375:794-8.
    1. Ma Y, Yang Y, Wang F, et al. Obesity and risk of colorectal cancer: a systematic review of prospective studies. PLoS One 2013;8:e53916.
    1. Arnold M, Pandeya N, Byrnes G, et al. Global burden of cancer attributable to high body-mass index in 2012: a population-based study. Lancet Oncol 2015;16:36-46.

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