Luteinizing hormone, its beta-subunit variant, and epithelial ovarian cancer: the gonadotropin hypothesis revisited.
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 (Trp(8)Arg and Ile(15)Thr) in its beta-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.
Akhmedkhanov
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A
Department of Obstetrics and Gynecology, New York University School of Medicine, 550 First Avenue, NB 9E2, New York, NY 10016, USA. akhmea01@med.nyu.edu
Toniolo
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P
Zeleniuch-Jacquotte
A
A
Pettersson
K S
KS
Huhtaniemi
I T
IT
D000328:Adult; D002277:Carcinoma / Q000097:blood* / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D006062:Gonadotropins / Q000097:blood*; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood*; D008875:Middle Aged; D020125:Mutation, Missense; D009519:New York City / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors
D006062:Gonadotropins; D007986:Luteinizing Hormone