Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC), Lyon, France.
Int J Cancer. 2020 Oct 1;147(7):1881-1894. doi: 10.1002/ijc.32980. Epub 2020 Apr 13.
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 RRs 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 RR 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 RRs 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 RR 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.
肥胖与结直肠癌（CRC）关联的潜在机制尚不完全清楚。本研究利用英国生物库（UK Biobank）的数据，探究 C 反应蛋白（CRP）、糖化血红蛋白（HbA1c）以及（联合）性激素结合球蛋白（SHBG）和睾酮在解释这种关联中的作用。采用序贯中介分析，将肥胖与正常体重（基于腰围、体重指数、腰臀比）对 CRC 风险的总效应分解为自然直接（NDE）和间接（NIE）效应。中位随访 7.1 年后，记录了 2070 例 CRC 病例（男性 1280 例，绝经后女性 790 例）。对于男性，腰围（≥102 与≤94cm）的校正风险比（RR）为 1.37（95%置信区间[CI]，1.19-1.58）。通过所有生物标志物，RR 为 1.08（95%CI：1.01-1.16），通过 CRP 影响的途径，RR 为 1.06（95%CI：1.01-1.11），通过 HbA1c 影响的途径（CRP 的潜在影响），RR 为 0.99（95%CI：0.97-1.01），通过 CRP、HbA1c 之外的 SHBG 和睾酮联合途径，RR 为 1.03（95%CI：0.99-1.08）。RR 为 1.26（95%CI：1.09-1.47）。对于女性，腰围（≥88 与≤80cm）的 RR 为 1.27（95%CI：1.07-1.50）。通过所有生物标志物，RR 为 1.08（95%CI：0.94-1.22），通过 CRP 影响的途径，RR 为 1.08（95%CI：0.99-1.17），通过 CRP 之外的 HbA1c 影响的途径，RR 为 1.00（95%CI：0.98-1.02），通过 CRP 和 HbA1c 之外的 SHBG 和睾酮联合途径，RR 为 1.00（95%CI：0.92-1.09）。RR 为 1.18（95%CI：0.96-1.45）。对于男性和女性，CRP 影响的途径仅解释了肥胖与 CRC 关联的一小部分。在男性中，睾酮和 SHBG 也解释了肥胖与 CRC 关联的一小部分。这些结果表明，这些肥胖相关因素所标记的途径可能不能解释肥胖与 CRC 关联的很大一部分。
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