GnRH and LHRgene variants predict adverse outcome in premenopausal breast cancer patients

Background Breast cancer development and progression are dependent on estrogen activity. In premenopausal women, estrogen production is mainly regulated through the hypothalamic-pituitary-gonadal (HPG) axis. Methods We have investigated the prognostic significance of two variants of genes involved i...

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Published inBreast cancer research : BCR Vol. 9; no. 4
Main Authors Piersma, Djura, Themmen, Axel PN, Look, Maxime P, Klijn, Jan GM, Foekens, John A, Uitterlinden, Andrñ G, Pols, Huibert AP, Berns, Els MJJ
Format Journal Article
LanguageEnglish
Published BioMed Central Ltd 10.08.2007
Subjects
Breast cancer
Cancer
Cancer patients
Development and progression
Estrogen
Genes
Genetic aspects
Glycoproteins
Hormones
Luteinizing hormone
Menopause
Oncology, Experimental
Patient outcomes
Prognosis
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Summary:Background Breast cancer development and progression are dependent on estrogen activity. In premenopausal women, estrogen production is mainly regulated through the hypothalamic-pituitary-gonadal (HPG) axis. Methods We have investigated the prognostic significance of two variants of genes involved in the HPG-axis, the GnRH (encoding gonadotropin-releasing hormone) 16Trp/Ser genotype and the LHR (encoding the luteinizing hormone receptor) insLQ variant, in retrospectively collected premenopausal breast cancer patients with a long follow-up (median follow-up of 11 years for living patients). Results Carriership was not related with breast cancer risk (the case control study encompassed 278 premenopausal cases and 1,758 premenopausal controls). A significant adverse relationship of the LHR insLQ and GnRH 16Ser genotype with disease free survival (DFS) was observed in premenopausal (hormone receptor positive) breast cancer patients. In particular, those patients carrying both the GnRH 16Ser and LHR insLQ allele (approximately 25%) showed a significant increased risk of relapse, which was independent of traditional prognostic factors (hazard ratio 2.14; 95% confidence interval 1.32 to 3.45; P = 0.002). Conclusion We conclude that the LHR insLQ and GnRH 16Ser alleles are independently associated with shorter DFS in premenopausal patients. When validated, these findings may provide a lead in the development of tailored treatment for breast cancer patients carrying both polymorphisms.
ISSN:1465-542X
1465-5411
1465-542X
DOI:10.1186/bcr1756