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Mediation of associations between adiposity and colorectal cancer risk by inflammatory and metabolic biomarkers
Author(s) -
Petimar Joshua,
Tabung Fred K.,
Valeri Linda,
Rosner Bernard,
Chan Andrew T.,
SmithWarner Stephanie A.,
Giovannucci Edward L.
Publication year - 2019
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.32047
Subject(s) - medicine , body mass index , waist , odds ratio , mediation , interquartile range , overweight , prospective cohort study , confidence interval , oncology , waist to height ratio , cancer , endocrinology , political science , law
Inflammation and hyperinsulinemia may drive associations between adiposity and colorectal cancer (CRC) risk, but few studies have examined this hypothesis using mediation analysis. We used inverse odds ratio weighting and logistic regression to calculate odds ratios (OR) and 95% confidence intervals (CI) for estimated total effects (OR TE ) of body mass index, waist circumference, and adult weight gain on CRC risk, and estimated effects operating through seven inflammatory and metabolic biomarkers (natural indirect effect; OR NIE ) or through paths independent of these biomarkers (natural direct effect; OR NDE ) among 209 CRC cases and 382 matched controls nested within the Health Professionals Follow‐up Study, a prospective cohort of male health professionals. A one‐interquartile range (IQR) increase in body mass index (3.6 kg/m 2 ) was associated with an OR TE of 1.40 (95% CI: 1.13, 1.73), which decomposed into an OR NIE of 1.26 (95% CI: 0.97, 1.52) and an OR NDE of 1.11 (0.87, 1.42), with possibly stronger mediation by these biomarkers for adult weight gain (IQR = 10.4 kg; OR TE = 1.32 [95% CI: 1.06, 1.64]; OR NIE = 1.47 [95% CI: 1.01, 1.81]; OR NDE = 0.89 [95% CI: 0.72, 1.11]), but no mediation for waist circumference. Mediation appeared to be stronger for the metabolic biomarkers than the inflammatory biomarkers. Inflammatory and metabolic mechanisms may mediate associations between both body mass index and adult weight gain with CRC risk.