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Pituitary Growth Hormone and Growth Hormone–Releasing Hormone Receptor Genes and Associations with Mammographic Measures and Serum Growth Hormone

¹ Ontario Cancer Genetics Network, Cancer Care Ontario; ² Division of Epidemiology and Statistics, Ontario Cancer Institute; ³ Imaging Research, Sunnybrook and Women's College Hospital Health Sciences Centre, Toronto, Ontario, Canada; and ⁴ the Robarts Research Institute, London, Ontario, Canada

Requests for reprints: Norman F. Boyd, Division of Epidemiology and Statistics, Ontario Cancer Institute, Room 10-415, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. Phone: 416-946-2942; Fax: 416-946-2024. E-mail: Boyd{at}uhnres.utoronto.ca

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 cm² (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).

Conclusion: 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.

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