Body size, IGF and growth hormone polymorphisms, and colorectal adenomas and hyperplastic polyps.

Abstract

OBJECTIVE:

We examined the risk of colorectal polyps in relation to body size factors and candidate polymorphisms in selected genes of insulin-like growth factor (IGF1) (rs5742612), IGF1 receptor (IGF1R) (rs2229765), IGF binding protein 3 (IGFBP3) (rs2854746) and growth hormone (GH1) (rs2665802).

DESIGN:

Cases with colorectal adenomas (n=519), hyperplastic polyps (n=691), or both lesions (n=227), and controls (n=772), aged 20-74 years, were recruited from patients who underwent colonoscopy between December 2004 and September 2007 at a large integrated-health plan in Washington state. Subjects participated in a 45-minute telephone interview to ascertain body size and physical activity, and provided a buccal DNA sample for genetic analysis. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable polytomous regression.

RESULTS:

Compared to those of normal weight, higher body mass index (BMI) was associated with elevated risk of colorectal adenomas (OR=1.65, 95% CI 1.22-2.25 BMI>or=30 kg/m(2), p-trend=0.002) and both lesions (OR=2.15, 95% CI 1.43-3.22 BMI>or=30 kg/m(2), p-trend=0.003), but there was no relationship with hyperplastic polyps. Obesity at age 18 and a weight gain of >or=21 kg since age 18 were also significantly associated with an increased risk of colorectal adenomas and both lesions, but not hyperplastic polyps. There was a reduced risk of colorectal adenomas (OR=0.63, 95% CI 0.42-0.94) and hyperplastic polyps (OR=0.7, 95% CI 0.5-0.9) associated with the homozygous variant genotype for GH1. Few meaningful results were evident for the other polymorphisms.

CONCLUSIONS:

There is an increased risk of colorectal adenomas and presence of both adenomas and hyperplastic polyps in relation to increasing body size. Some genetic variation in GH1 might contribute to a reduced risk of colorectal adenomas and hyperplastic polyps.

• Authors: Karen J Wernli, Polly A Newcomb, Yinghui Wang, Karen W Makar, Mazyar Shadman, Victoria M Chia, Andrea Burnett-Hartman, Michelle A Wurscher, Yingye Zheng, Margaret T Mandelson
• Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society (Growth Horm IGF Res) Vol. 20 Issue 4 Pg. 305-9 (Aug 2010) ISSN: 1532-2238 [Electronic] Scotland
• PMID: 20580999 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Human Growth Hormone
• Insulin-Like Growth Factor I

Topics

• Adenoma (genetics, pathology)
• Body Size (genetics)
• Colon (pathology)
• Colonic Polyps (genetics, pathology)
• Colorectal Neoplasms (genetics, pathology)
• Genetic Predisposition to Disease
• Human Growth Hormone (genetics)
• Humans
• Hyperplasia (genetics, pathology)
• Insulin-Like Growth Factor I (genetics)
• Polymorphism, Genetic