Pituitary growth hormone and growth hormone-releasing hormone receptor genes and associations with mammographic measures and serum growth hormone.
BACKGROUND
Mammographic density is a strong risk factor for breast cancer that is heritable and associated with blood levels of growth hormone and insulin-like growth factor-I (IGF-I). We tested single nucleotide polymorphisms (SNP) in pituitary growth hormone (GH1) and growth hormone-releasing hormone receptor (GHRHR) genes for an association with mammographic density, hormones of the growth hormone/IGF-I axis, and anthropometric variables.


METHODS
Mammograms from 348 women were measured using a computer-assisted method, blood collected, and DNA extracted. The SNPs genotyped were GH1 -57G>T, GH1 -75G >A, and GHRHR A57T. ANOVA and covariance were used to examine associations, adjusted for age, body mass index, ethnicity, and menopausal status, between each SNP and three measures of the mammogram: percent density, total dense area, and total nondense area. Similarly, the SNPs were tested for associations with serum growth hormone, IGF-I, IGFBP3, prolactin, and anthropometric variables.


RESULTS
GH1 -57G >T and GH1 -75G >A were both associated with percent density and total nondense area. GH1 -57T homozygotes had 5.2 more mean adjusted percent density than other subjects combined (P = 0.03) and 16.2 cm(2) (14.6%) less nondense area (P = 0.01). GH1 -75A homozygotes had 3.4 more percent density than subjects with at least one G allele (P = 0.04) and also had 32% higher serum growth hormone levels (P = 0.02).


CONCLUSIONS
We have found associations between mammographic density and two SNPs in the pituitary growth hormone gene, one of them also associated with serum growth hormone levels. These findings suggest that the GH1 gene may also influence breast cancer risk.
Mulhall
Cara
C
Division of Epidemiology and Statistics, Ontario Cancer Institute, Room 10-415, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9.
Hegele
Robert A
RA
Cao
Henian
H
Tritchler
David
D
Yaffe
Martin
M
Boyd
Norman F
NF
D000328:Adult; D000367:Age Factors; D015992:Body Mass Index; D001940:Breast / Q000033:anatomy & histology; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D013006:Growth Hormone / Q000097:blood / Q000235:genetics*; D013007:Growth Hormone-Releasing Hormone / Q000235:genetics*; D006801:Humans; D008327:Mammography; D008593:Menopause; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone