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

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 (GM) (rs2665802). Design: Cases with colorectal adenomas (n = 519), hyperplastic polyps (is = 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 (Cl) 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 >= 30 kg/m(2), p-trend = 0.002) and both lesions (OR = 2.15, 95% CI 1.43-3.22 BMI >= 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 >= 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. (C) 2010 Growth Hormone Research Society. Published by Elsevier Ltd. All rights reserved.