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

dc.contributor.author

Keku, Temitope O

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Vidal, Adriana

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Oliver, Shannon

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Hoyo, Catherine

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Hall, Ingrid J

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Omofoye, Oluwaseun

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McDoom, Maya

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Worley, Kendra

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Galanko, Joseph

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Sandler, Robert S

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Millikan, Robert

dc.coverage.spatial

Netherlands

dc.date.accessioned

2013-01-16T18:37:18Z

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2012-07

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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.

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http://www.ncbi.nlm.nih.gov/pubmed/22565227

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1573-7225

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https://hdl.handle.net/10161/6106

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eng

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Springer Science and Business Media LLC

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Cancer Causes Control

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10.1007/s10552-012-9981-2

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Cancer Causes and Control

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Adiponectin

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African Americans

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Aged

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C-Peptide

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Colonic Neoplasms

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European Continental Ancestry Group

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Female

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Gene Frequency

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Genetic Predisposition to Disease

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Genotype

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Genotyping Techniques

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Humans

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Insulin-Like Growth Factor Binding Protein 3

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Insulin-Like Growth Factor I

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Insulin-Like Growth Factor II

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Logistic Models

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Male

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Middle Aged

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Polymorphism, Genetic

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Risk Factors

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

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Journal article

duke.description.issue

7

duke.description.volume

23

pubs.author-url

http://www.ncbi.nlm.nih.gov/pubmed/22565227

pubs.begin-page

1127

pubs.end-page

1138

pubs.issue

7

pubs.organisational-group

Duke

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Faculty

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Published

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23

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