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 -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=1.7, 95% CI 1.2-2.3 BMI≥30 kg/m 2 , ptrend=0.002) and both lesions (OR=2.2, 95% CI 1.4-3.2 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=0.6, 95% CI 0.4-0.9) 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.

Adipokines and Obesity Are Associated with Colorectal Polyps in Adult Males: A Cross-Sectional Study

“…This is similar to at least one other report [25]. However, there are also reports of associations between some of these factors and the presence of hyperplastic polyps [26]–[28].…”

Lifestyle Risk Factors for Serrated Colorectal Polyps: A Systematic Review and Meta-analysis

“…Difficulties in measuring an individual's level of physical activity may be a possible explanation. Studies using MET-hours per week showed greater strength of association 42,44 , in comparison to those evaluating categorical variables such as ever v. never physical activity 49,81 .…”

“…Several studies have investigated SP risk in relation to genetic variants linked to the metabolism of the risk factors outlined such as alcohol 87 , smoking 88 ,body fatness 81 and diet 28,54,64 . However, only one study has investigated known CRC mutations -APC, KRAS and MSI interactions with lifestyle factors (namely, smoking status) and SP risk, and found that such mutations were only present in HP patients who smoked, and were not seen in non-smokers 41 .…”

Genetic variants in IGF-I, IGF-II, IGFBP-3, and adiponectin genes and colon cancer risk in African Americans and Whites

“…We previously showed that elevated fasting insulin levels predicted increased risk of adenomas or colon cancer precursors [4]. Several epidemiologic studies including case-control [5, 6, 7] and cohort studies [8–13] have also evaluated the relationship between colon cancer, IGFs, and factors related to obesity and insulin resistance [14]. While the majority of these studies have reported modest positive associations [10–12, 15], other reports have found no associations [9, 11].…”