1125 Body Fatness over the Life Course and the Risk of High-Risk Serrated Polyps and Advanced Conventional Adenomas

Abstract

INTRODUCTION: Obesity is an established risk factor for colorectal cancer. Serrated polyp (SP) and conventional adenoma (CA) represent two distinct groups of colorectal premalignancy. In contrast to the well-documented effect of adulthood obesity, the influence of early-life body fatness on the risk of developing SPs and CAs remains unclear. METHODS: This prospective study within the Nurses’ Health Study (1990-2012), the Nurses’ Health Study 2 (1991-2013), and the Health Professional Follow-up Study (1990-2010) collected detailed information on body fatness at different ages and the diagnosis of SPs and CAs. We individually examined the risk of high-risk SPs (≥10 mm or proximal SPs) and advanced CAs (≥10 mm or advanced histology) in relation to body fatness in early childhood (age 5), late childhood (age 10), early adulthood (age 18 for women and 21 for men), middle adulthood (baseline) and weight change from early adulthood to middle adulthood. Multivariable-adjusted logistic regression for clustered data was used to calculate the odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Among 29221 men and 132546 women in the three cohorts who had undergone at least one lower bowel endoscopy during 18-20 years of follow-up, we documented 3119 cases of high-risk SP and 3299 cases of advanced CA. The ORs of high-risk SPs and advanced CAs ranged from 1.12 (95% CI, 1.02-1.23) to 1.25 (95% CI, 1.10-1.42) in women who were obese in early and late childhood. The associations were attenuated after adjusting for adulthood BMI. Body fatness in middle adulthood showed a strong positive relationship with the risk of both types of CRC precursor lesion in men and women. Weight change from early adulthood to middle adulthood was associated with greater risk of high-risk SPs in women (OR comparing weight gain ≥20.0 kg to gain or loss < 2.0 kg, 1.39; 95% CI, 1.22-1.58) and men (OR, 1.40; 95% CI, 1.01-1.29), and advanced CAs in both women (OR, 1.14; 95% CI, 1.07-1.82) and men (OR, 1.21; 95% CI, 1.03-1.42). The associations were stronger for high-risk SPs than for advanced CAs in women (P heterogeneity = 0.01 for adulthood BMI, 0.004 for weight change). CONCLUSION: Weight gain during early adulthood and attained adiposity are associated with increased risk of high-risk SPs and advanced CAs in both men and women. There is heterogeneity in the associations among different types of colorectal precursor lesions in women but not in men. Body fatness in childhood is also associated with an increased risk in women.