Association of high birth weight with risk of early-onset colorectal cancer

Abstract

Background: Early-onset colorectal cancer (eoCRC), particularly rectal cancer, is increasing. We evaluated the association between high birth weight and eoCRC in a nested case-control study. Methods: We included patients aged 15-49 years diagnosed with colorectal adenocarcinoma at Kaiser Permanente Southern California (2009-2021). Cancer-free controls were matched 10:1 on age, sex, and length of health plan membership. Record linkage with California Department of Public Health’s birth registry was performed. Conditional logistic regression was used to evaluate associations between high birth weight, measured using (1) macrosomia (birth weight >4,000grams), and (2) large for gestational age (LGA; birth weight above the 90th percentile for gestational age and sex), and overall eoCRC, colon, and rectal cancer. Two-stage model adjustments were performed: first adjusting for pre-specified potential confounders, then adjusting for potential intermediates. Results: Of 1,400 eligible cases and matched 13,608 controls, 471 eoCRC cases (mean diagnosis age: 41.1 years) and 1,931 controls with linked birth certificate were included. Adjusted odds ratio (OR) for eoCRC was 1.32 (95% CI: 0.95-1.84) for macrosomia and 1.38 (0.97-1.98) for LGA. Macrosomia and LGA were associated with a marginal, non-statistically significant elevated risk of rectal cancer [OR (95%CI): 1.69 (0.97-2.97) and 1.81 (0.96-3.41), respectively], but not colon cancer [OR (95%CI): 1.18 (0.78-1.80) and 1.20 (0.77-1.86) for macrosomia and LGA, respectively]. Conclusions: An elevated risk of early-onset rectal cancer was suggested in individuals with high birth weight. Impact: The impact of intrauterine conditions on eoCRC risk should be further evaluated.