Haplotype-based analysis of common variation in the growth hormone receptor gene and prostate cancer risk.
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.
McKay
James D
JD
International Agency for Research on Cancer, Lyons, France.
Kaaks
Rudolf
R
Johansson
Mattias
M
Biessy
Carine
C
Wiklund
Fredik
F
Bälter
Katarina
K
Adami
Hans-Olov
HO
Boillot
Catherine
C
Gioia-Patricola
Lydie
L
Canzian
Federico
F
Stattin
Pär
P
Grönberg
Henrik
H
D000368:Aged; D016022:Case-Control Studies; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D012307:Risk Factors
D007334:Insulin-Like Growth Factor I