IGF2RGenetic Variants, Circulating IGF2 Concentrations and Colon Cancer Risk in African Americans and Whites

• DOI: 10.1155/2012/492068
• Publication Date: 2013-06-13T05:53:31Z
• Authors: Cathrine Hoyo; Susan K. Murphy; Joellen M. Schild...; Adriana C. Vidal; David Skaar; Robert C. Millikan; Joseph Galanko; Robert S. Sandler; Randy Jirtle; Temitope Keku
• Keywords: Adult; Male; Adenocarcinoma; Polymorphism, Single Nucleotide; Receptor, IGF Type 2; White People; 03 medical and health sciences; 0302 clinical medicine; Insulin-Like Growth Factor II; Risk Factors; Humans; Genetic Association Studies; Aged; Aged, 80 and over; 0303 health sciences; Homozygote; Sequence Analysis, DNA; Middle Aged; 3. Good health; Black or African American; Logistic Models; Colonic Neoplasms; Female; Other

TheMannose 6 Phosphate/Insulin-like Growth Factor Receptor-2 (IGF2R)encodes a type-1 membrane protein that modulates availability of the potent mitogen, IGF2. We evaluated the associations betweenIGF2Rnon-synonymous genetic variants (c.5002G>A, Gly1619Arg(rs629849), and c.901C>G, Leu252Val(rs8191754)), circulating IGF2 levels, and colon cancer (CC) risk among African American and White participants enrolled in the North Carolina Colon Cancer Study (NCCCS). Generalized linear models were used to compare circulating levels of IGF2 among 298 African American and 518 White controls. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association ofIGF2Rgenetic variants and CC risk. Women homozygous for theIGF2Rc.5002 G>A allele, had higher mean levels of circulating IGF2, 828 (SD=321) ng/ml compared to non-carriers, 595 (SD=217) ng/ml (p-value=0.01). This pattern was not apparent in individuals homozygous for theIGF2Rc.901 C>G variant. Whites homozygous for theIGF2Rc.901 C>G variant trended towards a higher risk of CC, OR=2.2 [95% CI(0.9–5.4)], whereas carrying theIGF2Rc.5002 G>A variant was not associated with CC risk. Our findings support the hypothesis that being homozygous for theIGF2Rc.5002 G>A modulates IGF2 circulating levels in a sex-specific manner, and while carrying theIGF2Rc.901 C>G may increase cancer risk, the mechanism may not involve modulation of circulating IGF2.