Published in:
01-07-2012 | Original paper
Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites
Authors:
Temitope O. Keku, Adriana Vidal, Shannon Oliver, Catherine Hoyo, Ingrid J. Hall, Oluwaseun Omofoye, Maya McDoom, Kendra Worley, Joseph Galanko, Robert S. Sandler, Robert Millikan
Published in:
Cancer Causes & Control
|
Issue 7/2012
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Abstract
Purpose
Evaluating genetic susceptibility may clarify effects of known environmental factors and also identify individuals at high risk. We evaluated the association of four insulin-related pathway gene polymorphisms in insulin-like growth factor-1 (IGF-I) (CA)
n
repeat, insulin-like growth factor-2 (IGF-II) (rs680), insulin-like growth factor–binding protein-3 (IGFBP-3) (rs2854744), and adiponectin (APM1 rs1501299) with colon cancer risk, as well as relationships with circulating IGF-I, IGF-II, IGFBP-3, and C-peptide in a population-based study.
Methods
Participants were African Americans (231 cases and 306 controls) and Whites (297 cases, 530 controls). Consenting subjects provided blood specimens and lifestyle/diet information. Genotyping for all genes except IGF-I was performed by the 5′-exonuclease (Taqman) assay. The IGF-I (CA)
n
repeat was assayed by PCR and fragment analysis. Circulating proteins were measured by enzyme immunoassays. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated by logistic regression.
Results
The IGF-I (CA)
19
repeat was higher in White controls (50 %) than African American controls (31 %). Whites homozygous for the IGF-I (CA)19 repeat had a nearly twofold increase in risk of colon cancer (OR = 1.77; 95 % CI = 1.15–2.73), but not African Americans (OR = 0.73, 95 % CI 0.50–1.51). We observed an inverse association between the IGF-II Apa1 A-variant and colon cancer risk (OR = 0.49, 95 % CI 0.28–0.88) in Whites only. Carrying the IGFBP-3 variant alleles was associated with lower IGFBP-3 protein levels, a difference most pronounced in Whites (p-trend <0.05).
Conclusions
These results support an association between insulin pathway-related genes and elevated colon cancer risk in Whites but not in African Americans.