Luteinizing hormone signaling and breast cancer: polymorphisms and age of onset
| Autor: | M. E. Kevenaar, Barry Iacopetta, Emjj Berns, Djura Piersma, Axel P. N. Themmen, Brenda Powell, I. L. van Staveren |
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| Přispěvatelé: | Medical Oncology, Internal Medicine |
| Rok vydání: | 2003 |
| Předmět: |
medicine.medical_specialty
Genotype medicine.drug_class Endocrinology Diabetes and Metabolism Clinical Biochemistry Mammary gland Breast Neoplasms Biology Biochemistry Polymerase Chain Reaction Endocrinology Breast cancer SDG 3 - Good Health and Well-being Gene Frequency Internal medicine medicine Humans Genetic Predisposition to Disease Allele Alleles Biochemistry (medical) Homozygote Age Factors Luteinizing Hormone Middle Aged Receptors LH medicine.disease Prognosis medicine.anatomical_structure Estrogen Female Gene polymorphism Age of onset Luteinizing hormone Polymorphism Restriction Fragment Length Signal Transduction |
| Zdroj: | Journal of Clinical Endocrinology and Metabolism, 88(4), 1653-1657. Endocrine Society |
| ISSN: | 0021-972X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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