| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Department of Surgery (B.L.P., B.J.I.), University of Western Australia, Nedlands 6907, Australia; and Departments of Medical Oncology (B.L.P., D.P., M.E.K., I.L.v.S., E.M.J.J.B.) and Internal Medicine (A.P.N.T.), Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands
Address all correspondence and requests for reprints to: Els M. J. J. Berns, Ph.D., Department of Medical Oncology, Josephine Nefkens Institute, Room Be 424, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands. E-mail: berns{at}bidh.azr.nl.
Estrogen exposure has repeatedly been shown to associate with the risk of developing breast cancer. Estrogen synthesis is under the control of LH and FSH, where LH, through its receptor (LHR), stimulates production of ovarian androgens; and FSH, their aromatization to estrogens. Here, we investigated whether functional polymorphic variants in the LH signaling pathway are associated with the risk of breast cancer or its clinical phenotype.
A PCR-restriction fragment length polymorphism genotyping approach was used to investigate this in 266 breast cancers. The LHR18insLQ allele does not seem to influence breast cancer risk. However, women who were homozygous for the LHR18insLQ allele were, on average, 8.3 yr younger at diagnosis, compared with those homozygous for the wild-type LHR allele (mean age, 51.9 yr vs. 60.2 yr; P = 0.03). Trends were observed for associations between LHR18insLQ carriers and nodal involvement or larger tumor size. Patients who were LHR18insLQ carriers revealed a significantly worse overall survival, compared with those who were homozygous for LHR [hazard ratio = 2.4; 95% CI (1.3–4.3); P = 0.006]. In contrast, no associations between the LH genotype and any of the clinical parameters were observed. Our findings suggest that the LHR18insLQ gene polymorphism determines an earlier age of disease onset and is prognostic for poor outcome of breast cancer.
This work was supported by grants from the Postgraduate Research Travel Award (Convocation, the University of Western Australia Graduates Association) and the John Nott Cancer Fellowship and Research Award (Cancer Foundation of Western Australia) (to B.L.P.).
B.L.P. and D.P. contributed equally to the manuscript.
Abbreviations: hCG, Human chorionic gonadotropin; HR, hazard ratio; LHR, LH receptor; RFLP, restriction fragment length polymorphism; SNP, single-nucleotide polymorphism.
This article has been cited by other articles:
 |
|
 |
|
  A. Kuorelahti, S. Rulli, I. Huhtaniemi, and M. Poutanen Human Chorionic Gonadotropin (hCG) Up-Regulates wnt5b and wnt7b in the Mammary Gland, and hCG{beta} Transgenic Female Mice Present with Mammary Gland Tumors Exhibiting Characteristics of the Wnt/{beta}-Catenin Pathway Activation Endocrinology, August 1, 2007; 148(8): 3694 - 3703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Udler, A.-T. Maia, A. Cebrian, C. Brown, D. Greenberg, M. Shah, C. Caldas, A. Dunning, D. Easton, B. Ponder, et al. Common Germline Genetic Variation in Antioxidant Defense Genes and Survival After Diagnosis of Breast Cancer J. Clin. Oncol., July 20, 2007; 25(21): 3015 - 3023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Piersma, E. M. J. J. Berns, M. Verhoef-Post, A. G. Uitterlinden, I. Braakman, H. A. P. Pols, and A. P. N. Themmen A Common Polymorphism Renders the Luteinizing Hormone Receptor Protein More Active by Improving Signal Peptide Function and Predicts Adverse Outcome in Breast Cancer Patients J. Clin. Endocrinol. Metab., April 1, 2006; 91(4): 1470 - 1476. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P N Themmen An update of the pathophysiology of human gonadotrophin subunit and receptor gene mutations and polymorphisms Reproduction, September 1, 2005; 130(3): 263 - 274. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
