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Background: The incidence of early-onset colorectal cancer (eoCRC) diagnosed among individuals under age 50 has been rising. However, risk factors for eoCRC are unclear. We investigated whether metabolic abnormalities are risk factors for eoCRC adenocarcinoma. Methods: Invasive colorectal adenocarcinoma cases diagnosed between ages 15 and 49 from 2008 to 2018 at Kaiser Permanente Southern California (KPSC) were identified. Those with a history of inflammatory bowel disease were excluded. Noncancer controls were selected 5:1 for each case matched by age, sex, and length of membership prior to index date. Data were collected from KSPC's electronic medical records. The exposures of interest included obesity, type II diabetes, hypertension, and dyslipidemia, assessed from ≥1 year prior to eoCRC diagnosis/index date. Conditional logistic regressions were used to evaluate the associations between these metabolic risk factors and risk of eoCRC adenocarcinoma, adjusting for race/ethnicity, smoking, family history, neighborhood socioeconomic status, and health care utilization. Results: A total of 1,032 cases and 5,128 controls were included. Risk of colorectal adenocarcinoma was significantly associated with obesity [odds ratio (OR) = 1.41; 95% confidence interval (CI), 1.15–1.74], but not diabetes, hypertension or dyslipidemia. In analysis stratified by tumor location, obesity was significantly associated with risk of colon adenocarcinoma OR = 1.56 (1.17–2.07), but its association with rectal adenocarcinoma was less clear OR = 1.19 (0.85–1.68). No significant interaction was detected between obesity and age (≥40 vs. &amp;lt;40), and obesity and sex. Conclusions: Obesity was associated with risk for eoCRC adenocarcinoma. Impact: This finding could help inform early-onset colorectal adenocarcinoma screening and prevention recommendations. See related commentary by Hayes, p. 1775

Metabolic Risk Factors Associated with Early-Onset Colorectal Adenocarcinoma: A Case–Control Study at Kaiser Permanente Southern California