Reproductive Hormones, Cancers, and Conditions in Relation to a Common Genetic Variant of Luteinizing Hormone

Abstract

A variant of the beta-subunit of luteinizing hormone (v-LH) is more common among populations also at higher risk for breast and ovarian cancer. To explore the possible relationship between these cancers and v-LH, we examined its frequency in premenopausal women, including 100 with a family history of ovarian cancer, 94 with carcinoma- in-situ of the breast, and 153 age and residence-matched controls. Reproductive histories were assessed and v-LH status measured by immunological assays from plasma drawn during the early follicular phase of cycles. For the entire study population, 283 (81.5%) were wild type; 61 (17.6%) were heterozygous; and three (0.9%) were homozygous for v-LH. Carrier frequency was not elevated among women with a family history of ovarian cancer or personal history of carcinoma-in-situ of the breast compared with controls. Women with the v-LH variant were less likely to report menstrual weight gain or ovarian cysts, more likely to report infertility, and have higher early follicular phase LH concentrations compared with women who were wild type. While there is no evidence from this study that v-LH increases risk for ovarian or breast cancer, we conclude that possession of v-LH may impact on some aspects of reproductive history and LH concentrations.