Haplotype-Based Analysis of Common Variation in the Growth Hormone Receptor Gene and Prostate Cancer Risk

Abstract

The growth hormone receptor (GHR) is potentially involved in prostate cancer through its role in stimulating insulin-like growth factor I production and its cellular effects on prostate epithelium. We have used a haplotype-based tagging approach within CAncer Prostate Sweden, a large retrospective case-control study of 2,863 cases and 1,737 controls to investigate if genetic variation in the GHR gene influences prostate cancer risk. One haplotype in the 3 ¶ region of the GHR gene was found associated with prostate cancer risk in elderly men (>65 years old at the time of diagnosis), with heterozygote haplotype carriers having an odds ratio of 1.65 (95% confidence interval, 1.21-2.16; P = 0.0009, P corrected = 0.03). GHR function has been implicated in the determination of body mass index. Interestingly, the same haplotype associated with risk in the 3 ¶ end of the GHR gene was also associated with a decrease in body mass index in controls (P = 0.003, P corrected = 0.05), possibly indicating some functionality with this haplotype. These results suggest that whereas genetic variation in the GHR gene does not seem to play a major role in prostate cancer etiology, one haplotype in the 3 ¶ region may be potentially relevant to cases with later onset of prostate cancer. (Cancer Epidemiol Biomarkers Prev 2007;16(1):169-73)

GHR exon 3 polymorphism: Association with type 2 diabetes mellitus and metabolic disorder

“…The genotype frequencies of the Swedish background population sample (of elderly men) in a previous report [10] are significantly different (p = 0.0009) from those of the NGT subjects reported here.…”

“…A previous study which investigated GHR exon 3 genotype distribution in the Swedish population [10] reports control genotype frequencies lower than ours, with genotype frequencies of 54% GHR fl/fl , 39% GHR fl/d3 and 7% GHR d3/d3 . These subjects were not randomly collected, but were rather matched as healthy controls to prostate cancer cases [21].…”

A Multi-Cohort Study of Polymorphisms in the GH/IGF Axis and Physical Capability: The HALCyon Programme

“…Our meta-analysis provided some evidence for lower weight and BMI among carriers of the exon-3 deletion of GHR . Although few specific investigations into the d3GHR polymorphism on population-based studies of adults have been conducted, smaller studies have found no associations with measures of body size (sample sizes ranged between 100 and 831) [46], [81], [82]; however, one study observed associations between its haplotypic block and BMI [46]. We therefore contacted the GIANT Consortium [83] to look up associations between tag SNPs of d3GHR and BMI.…”

Genetic variations at the human growth hormone receptor (GHR) gene locus are associated with idiopathic short stature

“…We prioritized SNPs previously shown to be in association with height , transcription regulation or disease risk (e.g. non‐small cell lung cancer or prostate cancer ).…”