. 2024 Mar 6;154(4):1069–1079. doi: 10.1016/j.tjnut.2024.03.002

TABLE 1.

Summary of published studies evaluating excess adiposity and EOCRC

Author; country	Study design	Study subjects	Summary of findings related to obesity and EOCRC incidence
Rogers et al. (2022); United States [56]	Cross-sectional	1856 EOCRC cases: % BMI >30 kg/m²: 29.28 % female: 47.3 Mean age, y: 41.11	Multivariate Poisson regression models for EOCRC incidence in Utah (2000–2020) among adults aged 18–49. Overall: incidence rate ratio (IRR) 1.00 (95% CI: 0.98, 1.02). Women: IRR 1.01 (95% CI: 0.98, 1.04). Men: IRR 0.99 (95% CI: 0.96, 1.01).
Hussan et al. (2020); United States [54]	Cross-sectional	All cancers: 1,272,243 Colorectal only: 1,184,980 %obese: 7.25	The number of patients with obesity undergoing CRC resections increased among all age groups, with the highest rise in the 18–49-y group [average annual percent change (AAPC) +13.1%, P < 0.001].
Sung et al. (2019); United States[55]	Cross-sectional	From 1995 to 2014, there were 14,672,409 incident cases for 30 types of cancers for 2,481,416,140 person-years of observation.	The incidences of cancers of the EOCRC increased in younger adults (25–49 y), with the magnitude of the increase’s steeper with younger age (all P_wald <0.05). IRR 25–29-y for EOCRC: 2.41% (95% CI: 0.57, 4.29).
Glover et al. (2019); United States [45]	Retrospective, cross-sectional study (Data from Explorys electronic medical record)	Total n = 34,606,650 of which 8,873,080 were 20–39 y old. ∗Limited to adults 20–39 y of age EOCRC: 1700 % female: 52 No EOCRC: 8,871,400 % female:59	EOCRC vs. no EOCRC for obesity: Odds Ratio (OR) 1.819 (95% CI: 1.618, 2.044), P < 0.001.
Elangovan et al. (2021); United States [46]	Retrospective, cross-sectional study Commercial database (Explorys, IBM Watson Health) on 57 million individuals ≥18 y who were active patients in the database in the last 5 y.	Among the 37,483,140 average-risk adults active in the database in the last 5 y, 162,150 individuals had at least one encounter diagnosis of malignant CRC.	Obesity was an independent risk factor for CRC across all age groups. OR between EOCRC and obesity in men only: • Age 20–9 y: adjusted OR 1.92 (95% CI: 1.85, 1.99). • Age 40–49 y: adjusted OR 1.96 (95% CI: 1.87, 2.06). OR between EOCRC and obesity in women only: • Age 20–39 y: adjusted OR 2.22 (95% CI: 1.84, 2.43). • Age 40–49 y: adjusted OR 1.49 (95% CI: 1.41, 1.57).
Sanford et al. (2020); United States [47]	Cross-sectional (Data from the National Health Institute Survey)	Overall sample (including CRC and EOCRC): 583,511 individuals, with 3173 cases. EOCRC specific: 321,736 individuals (age 18–49) with 239 cases.	OR between EOCRC (age 18–49) and BMI > 30 kg/m²: OR 1.39 (95% CI: 1.00, 1.92, P = 0.049).
Marx et al. (2022); United States [48]	Cross-sectional	21 individuals % BMI ≥ 30 kg/m²: 57 % female: 43	Identified tumors with high and low differential c-MYC proto-oncogene (MYC) expression. Patients with high-MYC tumors were overweight or obese (n = 4 for low MYC and n = 12 for high-MYC, P = 0.047).
Juo et al. (2018); United States [49]	Cross-sectional (Data from the California Cancer Registry Patient Discharge Database)	EOCRC sample: 112,024 % BMI ≥ 30 kg/m²: 5.7 % BMI ≥ 40 kg/m²: 1.9	Obese patients (BMI ≥ 30 kg/m²) had a younger onset age (−4.56 y ± SE 0.18, P < 0.05 when compared with nonobese patients) than nonobese patients. Morbidly obese patients (BMI ≥ 40 kg/m²) had an even younger onset age for EOCRC (−7.75 y ± SE 0.30, P < 0.05 when compared with nonobese).
Krigel et al. (2020); United States [58]	Retrospective, cross-sectional study (Single-center endoscopy database to identify symptomatic patients 18–49 y of age who underwent ambulatory colonoscopy)	Total n = 4333 363 patients (8.4%) with any EOCRC: 315 patients (7.3%) had colorectal adenomas and 48 patients (1.1%) had advanced neoplasia.	Any neoplasia: • OR for BMI 30–34.9 kg/m² compared with 18–24.9 kg/m²: 1.44 (95% CI: 1.04, 2.01, P = 0.029) • OR for BMI >35 kg/m² compared with 18–24.9 kg/m²: 1.32 (95% CI: 0.89, 1.95, P = 0.163) Adenoma: • OR for BMI 30–34.9 kg/m2 compared with 18–24.9 kg/m2: 1.45 (95% CI: 1.02, 2.07, P = 0.037) • OR for BMI >35 kg/m² compared with 18–24.9 kg/m²: 1.24 (95% CI: 0.81, 1.89, P = 0.332)
Glenn et al. (2018); United States [52]	Cross-sectional	156 survivors (106 breast, 50 colorectal) Mean BMI, kg/m²: 26.5 % female: 83 Mean age, y: 49.6	Prevalence presented: 24% with obesity (BMI ≥ 30 kg/m²), 31% overweight (BMI ≥ 25 kg/m²), 44% with a normal BMI (BMI < 25 kg/m²), and 1% underweight (BMI <18.5 kg/m²).
Wolbert et al. (2018); United States [50]	Cross-sectional	N = 137 (24 EOCRC, 113 CRC). EOCRC: 24 % female: 50 Mean age, y: 43.1 CRC: 113 % female: 38.1 Mean age, y: 64	Number of obese (BMI >30 kg/m²) patients in the younger cohort was statistically higher than the older group (P < 0.001).
Kim et al. (2022); South Korea [51]	Cross-sectional	2,023 with EOCRC and 11,598 without EOCRC at colonoscopy. With EOCRC: 2023 % obese according to BMI: 41.2 % female: 24.7 Mean age, y: 35.7 Without EOCRC: 11,598 % obese according to BMI: 28.7 % female: 40.5 Mean age, y: 35.0031	OR between EOCRC and obesity: OR 1.439 (95% CI: 1.133, 1.828), P = 0.003
Lee et al. (2016); South Korea [57]	Cross-sectional	Total n = 2819 Age group: <40 % female: 33 Mean BMI: 23.1 Age group: 40–44 % female: 25 Mean BMI: 23.8 Age group: 45–49 % female: 26.1 Mean BMI: 24 Age group: ≥50 % female: 32.3 Mean BMI: 24	Multivariate analysis OR colorectal adenoma in young adults with BMI >30 kg/m² vs. BMI 18.5–24.9 kg/m²: OR 0.55 (95% CI: 0.24, 1.27, P = 0.161). Univariate analysis OR colorectal advanced adenoma in young adults with BMI >30 kg/m² vs. BMI < 25 kg/m²: OR 1.16 (95% CI: 0.56, 2.4, P = 0.862).
Bohorquez et al. (2016); Colombia [53]	Cross-sectional	N = 1525 % female: 53.2 Age of onset: % EOCRC ( $\geq$ 50 y):26.6 % CRC: 73.4 % obese: 33.6	No difference in obesity prevalence between CRC and EOCRC (34.7% vs. 30%, respectively; P = 0.478).
Clinton et al. (2022); United States [66]	Retrospective predictive study—Machine learning predictive study	3116 adults aged 35–50 at average-risk for CRC and underwent colonoscopy between 2017 and 2020 at a single center. Prediction outcomes were 1) CRC and 2) CRC or high-risk polyps.	The most important predictive variables in the regularized discriminant analysis Model for EOCRC or high-risk polyps were income per zip code, the colonoscopy indication, and BMI quartiles.
Low et al. (2020); United States [61]	Case-control	EOCRC cases: 651 Mean BMI, kg/m²: 29.5 % female: 8.8 Mean age, y: 44.8 Controls: 67,416 Mean BMI kg/m²: 30 % female: 17.8 Mean age, y: 43.2	Obesity was significantly associated with decreased EOCRC odds [odds ratio (OR): 0.7; 95% CI: 0.56, 0.86].
Gausman et al. (2020); United States [60]	Case-control	EOCRC cases: 269 Mean BMI, kg/m²: 27 % female: 46 Mean age, y: 43 Controls: 1122 Mean BMI kg/m²: 28 % female: 55 Mean age, y: 45	Did not observe an association between obesity and EOCRC (OR 0.98; 95% CI: 0.95, 1.00).
Li et al. (2022); Germany [39]	Case-control	Overall sample combining CRC and EOCRC: 6602 patients with EOCRC/CRC and 7950 matched controls EOCRC specific sample: EOCRC cases: 747 % female: 43 EOCRC Controls: 621 % female: 44	OR between EOCRC and obesity classification at 20 y of age: OR 2.56 (95% CI: 1.20, 5.44). OR between EOCRC and obesity classification at 30 y of age: OR 2.06 (95% CI: 1.25, 3.40). OR between EOCRC and obesity classification ∼10 y before diagnosis: OR 1.88 (95% CI: 1.30, 2.73).
Schumacher et al. (2021); United States [59]	Case-control	1032 cases and 5128 controls. EOCRC cases: 1032 % obese according to BMI: 48.5 % female: 50.1 Controls: 5,128 % obese according to BMI: 39.4 % female: 49.9	Risk of colorectal adenocarcinoma was significantly associated with obesity (OR 1.41; 95% CI: 1.15, 1.74), but not diabetes, hypertension, or dyslipidemia. Tumor location: obesity significantly associated with risk of colon adenocarcinoma OR 1.56 (95% CI: 1.17, 2.07). No significant interaction was detected between obesity and age (≥40 vs. <40), and obesity and sex.
Liu et al. (2019); United States [62]	Prospective cohort study	85,256 women studied with 114 EOCRC cases observed.	Multivariable relative risk was 1.93 (95% CI: 1.15, 3.25) for women with obesity (BMI ≥ 30.0).
Syed et al. (2019); United States [63]	Population-based cohort analysis	Overall sample: 35,493,980. 68,860 patients (0.2%) were identified with CRC, of which 5710 (8.3%) were younger than 50 y old (EOCRC diagnosis). EOCRC specific: % BMI ≥ 30kg/m²: 61 % female: 51	OR EOCRC vs. CRC for obesity: OR 1.14 (95% CI: 1.08, 1.20, P < 0.001) OR EOCRC vs. control for obesity: OR 2.88 (95% CI: 2.74, 3.04, P < 0.001)
Park et al. (2022); United States [64]	Retrospective observational study	Patients with EOCRC: 3856% female: 47.5 Mean age, y: 43	Presented prevalence of new EOCRC only. % with obesity (BMI >30 kg/m²): 26.9
Hussan, et al. (2020); United States [65]	Retrospective cohort study	N = 30,279 7.4% (2238) with a prior history of bariatric surgery (cases). % female: 77.4 % diagnosed CRC:91.6 92.6% (28,041) were nonbariatric morbidly obese (controls). % female: 57.1 % diagnosed CRC: 92.6	The steepest rise in EOCRC resections was after bariatric surgery vs. a lesser increase in morbid obesity controls (AAPC +18.7% and +13.7%, respectively, P < 0.001).

Abbreviations: AAPC, average annual percent change; AOR, adjusted odds ratio; EOCRC, early-onset colorectal cancer; ERCN, early-onset neoplasia; IRR, incidence rate ratio; MYC, c-MYC proto-oncogene; OR, odds ratio.