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

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).

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.

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.

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.