RGD Reference Report - GnRH and LHR gene variants predict adverse outcome in premenopausal breast cancer patients. - Rat Genome Database

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GnRH and LHR gene variants predict adverse outcome in premenopausal breast cancer patients.

Authors: Piersma, D  Themmen, AP  Look, MP  Klijn, JG  Foekens, JA  Uitterlinden, AG  Pols, HA  Berns, EM 
Citation: Piersma D, etal., Breast Cancer Res. 2007;9(4):R51.
RGD ID: 2292541
Pubmed: PMID:17692113   (View Abstract at PubMed)
PMCID: PMC2206727   (View Article at PubMed Central)
DOI: DOI:10.1186/bcr1756   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GNRH1Humanbreast cancer severityIAGP DNA:SNP:CDS:16Ser allele associated with decreased disease free survival alone (p=0.05) or in combination with the insLQ allele of LHCGR (p=0.001)RGD 
Gnrh1Ratbreast cancer severityISOGNRH1 (Homo sapiens) RGD 
Gnrh1Mousebreast cancer severityISOGNRH1 (Homo sapiens) RGD 
LHCGRHumanbreast cancer severityIAGP DNA:insertion:CDS:insLQ allele associated with decreased disease free survival alone (p=0.007) or in combination with the 16Ser allele of GNRH1 (p=0.001)RGD 
LhcgrRatbreast cancer severityISOLHCGR (Homo sapiens) RGD 
LhcgrMousebreast cancer severityISOLHCGR (Homo sapiens) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gnrh1  (gonadotropin releasing hormone 1)
Lhcgr  (luteinizing hormone/choriogonadotropin receptor)

Genes (Mus musculus)
Gnrh1  (gonadotropin releasing hormone 1)
Lhcgr  (luteinizing hormone/choriogonadotropin receptor)

Genes (Homo sapiens)
GNRH1  (gonadotropin releasing hormone 1)
LHCGR  (luteinizing hormone/choriogonadotropin receptor)


Additional Information