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American Journal of Epidemiology Vol. 154, No. 1 : 43-49
Copyright © 2001 by The Johns Hopkins University School of Hygiene and Public Health


ORIGINAL CONTRIBUTIONS

Luteinizing Hormone, Its ß-Subunit Variant, and Epithelial Ovarian Cancer: The Gonadotropin Hypothesis Revisited

Arslan Akhmedkhanov1,2, Paolo Toniolo1,2, Anne Zeleniuch-Jacquotte2, Kim S. Pettersson3 and Ilpo T. Huhtaniemi4

Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY.
Department of Environmental Medicine, New York University School of Medicine, New York, NY.
Department of Biotechnology, University of Turku, Finland.
Department of Physiology, University of Turku, Finland.

The gonadotropin hypothesis postulates that excessive gonadotropin stimulation results in increased proliferation and subsequent malignant transformation of ovarian epithelium. The authors evaluated this hypothesis by analyzing the association between serum levels of wild-type luteinizing hormone (LH) and ovarian cancer risk. They also examined the relation between a variant of LH containing two missense point mutations (Trp8Arg and Ile15Thr) in its ß-subunit and ovarian cancer risk. Fifty-eight cases of epithelial ovarian cancer and 116 controls matched on age, menopausal status, and date of blood donation were included in a case-control study nested within the New York University Women's Health Study, a prospective cohort enrolled between 1985 and 1991 in New York City. Wild-type serum levels and variant LH status were determined by immunofluorometric assays in which monoclonal antibodies specific for wild-type and variant LH were used. Compared with women in the lowest tertile of wild-type LH, women in the highest tertile had a lower risk of ovarian cancer, after adjustment for potential confounders (odds ratio = 0.42, 95% confidence interval: 0.09, 2.09). Women heterozygous for variant LH were not at increased risk (adjusted odds ratio = 0.95, 95% confidence interval: 0.27, 3.34). The results suggest that neither wild-type LH levels nor variant LH status is associated with increased risk of epithelial ovarian cancer.

gonadotropins; LH; ovarian neoplasms; polymorphism (genetics)

Abbreviations: CI, confidence interval; FSH, follicle-stimulating hormone; LH, luteinizing hormone; OR, odds ratio


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