Data from Body Size, Physical Activity, Early-Life Energy Restriction, and Associations with Methylated Insulin-like Growth Factor–Binding Protein Genes in Colorectal Cancer

Abstract

<div>Abstract<p><b>Background:</b> We investigated body size, physical activity, and early-life energy restriction in relation to colorectal tumors with and without methylated insulin-like growth factor–binding protein (<i>IGFBP</i>) genes, which are putative tumor-suppressor genes.</p><p><b>Methods:</b> We determined <i>IGFBP2</i>, <i>IGFBP3</i>, and <i>IGFBP7</i> promoter CpG island hypermethylation in tumors of 733 colorectal cancer cases from the Netherlands Cohort Study (<i>N</i> = 120,852). Participants self-reported lifestyle and dietary factors at baseline in 1986. Using a case–cohort approach (<i>N</i> subcohort = 5,000), we estimated hazard ratios (HR) for colorectal cancer by extent of <i>IGFBP</i> methylation.</p><p><b>Results:</b> Comparison of the highest versus lowest sex-specific tertiles of adult body mass index (BMI) gave multivariable-adjusted HRs [95% confidence intervals (CI)] for colorectal cancers with 0 (18.7%), 1 (29.5%), 2 (32.4%), and 3 (19.5%) methylated genes of 1.39 (0.88–2.19), 1.11 (0.77–1.62), 1.67 (1.17–2.38), and 2.07 (1.29–3.33), respectively. Other anthropometric measures and physical activity were not associated with colorectal cancer risk by extent of <i>IGFBP</i> methylation, except height in sex-specific analyses for women. Exposure to energy restriction during the Dutch Hunger Winter versus nonexposure gave HRs (95% CIs) for colorectal cancers with 0, 1, 2, and 3 methylated genes of 1.01 (0.67–1.53), 1.03 (0.74–1.44), 0.72 (0.52–0.99), and 0.50 (0.32–0.78), respectively.</p><p><b>Conclusions:</b> Adult BMI, height (in women only), and early-life energy restriction were associated with the risk of having a colorectal tumor characterized by <i>IGFBP</i> methylation.</p><p><b>Impact:</b> Body size may particularly increase the risk of <i>IGFBP</i> gene–methylated colorectal tumors; this finding might facilitate more targeted approaches to prevent obesity-related colorectal cancers. <i>Cancer Epidemiol Biomarkers Prev; 23(9); 1852–62. ©2014 AACR</i>.</p></div>