Baxter

Casparie

Coen D.A. Stehouwer

Colinda C.J.M. Simons

Derks

Goldbohm

Hughes

Jass

Manon van Engeland

Matty P. Weijenberg

Ogino

Piet A. van den Brandt

Suzuki

Abstract
               Background: 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 (IGFBP) genes, which are putative tumor-suppressor genes.
               Methods: We determined IGFBP2, IGFBP3, and IGFBP7 promoter CpG island hypermethylation in tumors of 733 colorectal cancer cases from the Netherlands Cohort Study (N = 120,852). Participants self-reported lifestyle and dietary factors at baseline in 1986. Using a case–cohort approach (N subcohort = 5,000), we estimated hazard ratios (HR) for colorectal cancer by extent of IGFBP methylation.
               Results: 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 IGFBP 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.
               Conclusions: Adult BMI, height (in women only), and early-life energy restriction were associated with the risk of having a colorectal tumor characterized by IGFBP methylation.
               Impact: Body size may particularly increase the risk of IGFBP gene–methylated colorectal tumors; this finding might facilitate more targeted approaches to prevent obesity-related colorectal cancers. Cancer Epidemiol Biomarkers Prev; 23(9); 1852–62. ©2014 AACR.</jats:p

Crossref

Cancer Epidemiology Biomarkers & Prevention

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

http://cebp.aacrjournals.org/content/cebp/23/9/1852.full.pdf

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

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