Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

• Published in: Cancer causes & control Vol. 23; no. 7; pp. 1127 - 1138
• Main Authors: Keku, Temitope O., Vidal, Adriana, Oliver, Shannon, Hoyo, Catherine, Hall, Ingrid J., Omofoye, Oluwaseun, McDoom, Maya, Worley, Kendra, Galanko, Joseph, Sandler, Robert S., Millikan, Robert
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer 01.07.2012; Springer Netherlands; Springer Nature B.V
• Subjects: Adiponectin - genetics; Adiponectin - metabolism; African Americans; African Americans - genetics; Aged; Alleles; Apoptosis; Biological markers; Biomedical and Life Sciences; Biomedicine; C-Peptide - blood; Cancer Research; Colonic Neoplasms - blood; Colonic Neoplasms - ethnology; Colonic Neoplasms - genetics; Colorectal cancer; Cytokines; Epidemiology; European Continental Ancestry Group - genetics; Female; Gene Frequency; Genes; Genetic Predisposition to Disease - ethnology; Genetic Predisposition to Disease - genetics; Genotype; Genotypes; Genotyping Techniques - methods; Hematology; Humans; Insulin; Insulin resistance; Insulin-Like Growth Factor Binding Protein 3 - genetics; Insulin-Like Growth Factor Binding Protein 3 - metabolism; Insulin-Like Growth Factor I - genetics; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor II - genetics; Insulin-Like Growth Factor II - metabolism; Insulin-like growth factors; Logistic Models; Male; Medical genetics; Middle Aged; Oncology; Original Paper; Peptides; Polymorphism; Polymorphism, Genetic; Proteins; Public Health; Race; Risk Factors; Somatomedins; Type 2 diabetes mellitus; North Carolina; United States > US; African Americans; IGF; Colon cancer; Insulin; Polymorphism
• ISSN: 0957-5243; 1573-7225; 1573-7225
• DOI: 10.1007/s10552-012-9981-2

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 (APMI 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 Apal 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.