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Sci Rep. 2015 Sep 18;5:14126. doi: 10.1038/srep14126.

Genetic Variants in the Insulin-like Growth Factor Pathway and Colorectal Cancer Risk in the Netherlands Cohort Study.

Author information

1
Department of Epidemiology, GROW - School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
2
Department of Toxicology, NUTRIM - School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, the Netherlands.
3
Department of Pathology, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Centre, Maastricht, the Netherlands.

Abstract

Interrelationships between insulin-like growth factors (IGFs), hyperinsulinaemia, diabetes, and colorectal cancer (CRC) indicate involvement of IGFs in colorectal tumorigenesis. We investigated the CRC risk associated with 24 single nucleotide polymorphisms (SNPs) in 9 genes related to the IGF pathway and an IGF1 19-CA repeat polymorphism. Variants were selected from literature and genotyped in toenail DNA from 3,768 subcohort members and 2,580 CRC cases from the Netherlands Cohort Study, which has a case-cohort design (n = 120,852). We used the follow-up period 1986-2002. Eighteen SNPs were unequivocally associated with selected endpoints in the literature and unfavorable alleles were aggregated into a genetic sum score. Cox regression showed that a higher genetic sum score significantly increased CRC risk at all subsites, except the rectum, in men (highest vs. lowest tertile: HR for CRC = 1.36, 95% CI: 1.11, 1.65; P-trend = 0.002). Single SNPs (except the IGF1 SNP rs5742694) were not associated with risk. Models including the total number of IGF1 19-CA repeats showed CRC risk was halved at all subsites in women carrying < 38 repeats but not > 38 repeats (≤ 36 versus 38 repeats: HR for CRC = 0.44; 95% CI: 0.33, 0.58; P-trend < 0.001). These findings support a role for variants in IGF-related genes in colorectal tumorigenesis.

PMID:
26381944
PMCID:
PMC4585376
DOI:
10.1038/srep14126
[Indexed for MEDLINE]
Free PMC Article

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