Body size, physical activity, early life energy restriction, and associations with methylated insulin-like growth factor binding protein genes in colorectal cancer
Menée aux Pays-Bas auprès de 120 852 participants, cette étude de cohorte évalue l'association entre la taille, l'activité physique, une restriction énérgétique alimentaire tôt dans la vie et le risque de cancer colorectal caractérisé par la méthylation des gènes IGFBP
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 CRC 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 for CRC by extent of IGFBP methylation. Results: Comparison of the highest versus lowest sex-specific tertiles of adult body mass index (BMI) gave multivariable-adjusted hazard ratios (95% confidence intervals (CIs)) for CRCs 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 CRC risk by extent of IGFBP methylation, except height in sex-specific analyses for women. Exposure to energy restriction during the Dutch Hunger Winter versus non-exposure gave HRs (95% CIs) for CRCs 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 predicts preferentially for IGFBP gene methylated colorectal tumors, which might facilitate more targeted approaches to prevent obesity-related colorectal cancers.