Quick Search:

uzh logo
Browse by:
bullet
bullet
bullet
bullet

Zurich Open Repository and Archive

Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-16062

Wong, H L; Koh, W P; Probst-Hensch, N M; Van den Berg, D; Yu, M C; Ingles, S A (2008). Insulin-like growth factor-1 promoter polymorphisms and colorectal cancer: a functional genomics approach. Gut, 57(8):1090-1096.

[img] PDF - Registered users only
1MB

View at publisher
[img]
Preview
Accepted Version
PDF
1MB

Abstract

RATIONALE: Insulin-like growth factor-1 (IGF1) has been proposed to mediate the obesity-related carcinogenic effects of "Western lifestyle". While genetic factors explain at least half of inter-individual IGF1 variation, the IGF1 polymorphisms hypothesised to underlie the variation in cancer incidence rates remain ill-defined. METHODS: We used a comparative genomics approach to identify putative regulatory polymorphisms in the IGF1 promoter region within a rapidly westernising population, the Singapore Chinese. Association of IGF1 genotype with colorectal cancer risk was assessed among 298 colorectal cancer cases and 1142 controls nested within the Singapore Chinese Health Study. RESULTS: We identified a common (minor allele frequency = 0.36) single-nucleotide polymorphism (SNP), IGF1-2995 C/A, within a consensus domain for an octamer binding factor (Oct1/Oct2) transcription factor binding site. Possession of one or two copies of the minor allele (genotypes AA and CA) conferred an approximate 40% decrease in risk in comparison to genotype CC (odds ratio, 0.59; 95% confidence interval, 0.45 to 0.77). This association was stronger for colon cancer than for rectal cancer (p(heterogeneity)<0.001) and for those who were physically active versus inactive (p(interaction) = 0.05). Models including other previously identified promoter polymorphisms did not provide a better prediction of colorectal cancer risk. CONCLUSIONS: Our results support the hypotheses that IGF1 plays a role in colonic carcinogenesis and that genetically inherited variation in IGF1 expression influences risk of colorectal cancer.

Citations

20 citations in Web of Science®
19 citations in Scopus®
Google Scholar™

Altmetrics

Downloads

20 downloads since deposited on 25 Feb 2009
8 downloads since 12 months

Detailed statistics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Institute of Surgical Pathology
DDC:610 Medicine & health
Language:English
Date:2008
Deposited On:25 Feb 2009 16:14
Last Modified:27 Nov 2013 22:51
Publisher:BMJ Publishing Group
ISSN:0017-5749
Publisher DOI:10.1136/gut.2007.140855
PubMed ID:18308828

Users (please log in): suggest update or correction for this item

Repository Staff Only: item control page