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 (GH1) (rs2665802).


METHODS
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.
Wernli
Karen J
KJ
Program in Cancer Prevention, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. kwernli@fhcrc.org
Newcomb
Polly A
PA
Wang
Yinghui
Y
Makar
Karen W
KW
Shadman
Mazyar
M
Chia
Victoria M
VM
Burnett-Hartman
Andrea
A
Wurscher
Michelle A
MA
Zheng
Yingye
Y
Mandelson
Margaret T
MT
D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D049628:Body Size / Q000235:genetics*; D003106:Colon / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D020022:Genetic Predisposition to Disease; D019382:Human Growth Hormone / Q000235:genetics; D006801:Humans; D006965:Hyperplasia / Q000235:genetics / Q000473:pathology; D007334:Insulin-Like Growth Factor I / Q000235:genetics; D011110:Polymorphism, Genetic
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I