title: GnRH and LHR gene variants predict adverse outcome in premenopausal breast cancer patients.
abstract: 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).
  
  
  CONCLUSIONS
  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.
authors: Department of Internal Medicine, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
authors: Djura
authors: D
authors: Piersma
authors: Axel P N
authors: AP
authors: Themmen
authors: Maxime P
authors: MP
authors: Look
authors: Jan G M
authors: JG
authors: Klijn
authors: John A
authors: JA
authors: Foekens
authors: André G
authors: AG
authors: Uitterlinden
authors: Huibert A P
authors: HA
authors: Pols
authors: Els M J J
authors: EM
authors: Berns
mesh_terms: D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000601:surgery; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D007987:Gonadotropin-Releasing Hormone / Q000235:genetics*; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017697:Premenopause; D011960:Receptors, Estrogen; D011974:Receptors, LH / Q000235:genetics*; D012189:Retrospective Studies; D015996:Survival Rate; D013629:Tamoxifen / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D011974:Receptors, LH; D013629:Tamoxifen; D007987:Gonadotropin-Releasing Hormone
references: Oncol Rep. 2002 Sep-Oct;9(5):1127-32
references: 12168084
references: J Endocrinol. 2002 Apr;173(1):1-11
references: 11927379
references: J Clin Endocrinol Metab. 2003 Apr;88(4):1653-7
references: 12679452
references: Mutat Res. 2003 Sep;544(1):9-41
references: 12888106
references: Hum Mutat. 2003 Oct;22(4):261-74
references: 12955713
references: J Clin Endocrinol Metab. 2004 Jun;89(6):2763-9
references: 15181055
references: J Clin Endocrinol Metab. 1977 Feb;44(2):356-60
references: 320223
references: Nature. 1985 Jan 17-23;313(5999):231-3
references: 2982100
references: J Clin Endocrinol Metab. 1990 May;70(5):1233-8
references: 2186053
references: Mol Cell Endocrinol. 1995 Jun;111(2):113-23
references: 7556872
references: Cancer. 1996 Jan 1;77(1):97-103
references: 8630946
references: Int J Cancer. 1997 May 16;71(4):595-9
references: 9178813
references: Biometrics. 1997 Dec;53(4):1253-61
references: 9423247
references: Osteoporos Int. 1998;8(5):404-9
references: 9850346
references: Breast Cancer Res Treat. 2004 Oct;87(3):255-64
references: 15528968
references: JAMA. 2004 Dec 22;292(24):2991-6
references: 15613667
references: J Clin Oncol. 2005 Mar 10;23(8):1736-50
references: 15755982
references: Oncologist. 2006 Feb;11(2):111-25
references: 16476832
references: J Cancer Res Clin Oncol. 2006 May;132(5):275-86
references: 16435142
references: J Clin Endocrinol Metab. 2006 Apr;91(4):1470-6
references: 16464948
references: Nat Rev Cancer. 2006 Nov;6(11):886-93
references: 17036039
references: J Natl Cancer Inst. 2000 Jun 7;92(11):903-11
references: 10841825
references: Lancet. 2000 May 27;355(9218):1869-74
references: 10866443
references: J Natl Cancer Inst. 2000 Jul 19;92(14):1126-35
references: 10904085
references: Gynecol Oncol. 2000 Aug;78(2):194-202
references: 10926802
references: N Engl J Med. 2001 Jan 25;344(4):276-85
references: 11172156
references: J Clin Oncol. 2001 Jan 15;19(2):343-53
references: 11208825
references: Cancer Res. 2002 Feb 15;62(4):1036-44
references: 11861379
references: Bone. 2003 Feb;32(2):185-90
references: 12633791