OA Epidemiology

IGF polymorphisms modify associations between energy balance and colorectal cancer risk: the importance of extensive environmental exposure data and aggregated genetic variants

Proceedings of the 2013 annual meeting of the Netherlands Epidemiology Society

Volume 1 Issue S1 Abstract 57

 

C.C.J.M. Simons, GROW, Maastricht University, Maastricht, the Netherlands
L.J. Schouten, GROW, Maastricht University, Maastricht, the Netherlands
R. Godschalk, NUTRIM, Maastricht University, Maastricht, the Netherlands
M. van Engeland, GROW, Maastricht University, Maastricht, the Netherlands
P.A. van den Brandt, GROW, Maastricht University, Maastricht, the Netherlands
F.J. van Schooten, NUTRIM, Maastricht University, Maastricht, the Netherlands
M.P Weijenberg, GROW, Maastricht University, Maastricht, the Netherlands

Background
Gene-environment interactions between variants in growth-regulating IGF genes and energy balance in colorectal cancer (CRC) were studied in the Netherlands Cohort Study (NLCS) after 16.3 years follow-up.

Methods
Using a systematic strategy, we selected 25 SNPs and a CA repeat in IGF genes that had repeatedly demonstrated significant associations with CRC risk, energy balance-related exposures or related endpoints in literature, and thus likely modify effects of energy balance on CRC development. Twenty-four SNPs were successfully genotyped in toenail DNA of NLCS subcohort members (n=3,203) and CRC cases (n=2,274) with adequate environmental data. Unfavorable alleles were aggregated into a sum score. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated in case-cohort analyses for linear combinations between tertiles of the genetic sum score and 8 energy balance-related exposures.

Results
Significant and increasingly higher risks were observed for men with more adverse profiles. In particular carrying more unfavorable alleles in combination with a larger adult trouser/skirt size, an increased height or the absence of early life energy restriction during the Hunger Winter was associated with distal colon cancer [highest vs. lowest linear combinations: HR (95% CI) = 2.03 (1.27–3.24),  2.05 (1.16–3.63)  and 1.87 (1.11–3.16), respectively]. A combined effect of IGF polymorphisms and energy balance-related exposures on subsite-specific CRC risk was less convincing in women.

Conclusion
Combined effects of IGF polymorphisms and specific energy balance-related exposures are important in CRC development in men. The availability of extensive environmental data and the aggregation of genetic variants were invaluable for interpreting gene-environment interactions.

Published: 06 Jun, 2013

 
Licensee OA Publishing London 2013. Creative Commons Attribution License (CC-BY)