Do Steroid Hormones Play a Role in the Etiology of Glioma?

Abstract

Gliomas are the most common type of primary malignant brain tumor and have a very poor prognosis. Little is known, however, about the etiology of these tumors. Evidence from a number of sources suggests that endogenous steroid hormones may play a role in the development of gliomas. First, the descriptive epidemiology of glioma suggests a relative protection of females compared with males, particularly during the premenopausal years. Second, some gliomas and glioblastomas express estrogen receptors (ER), especially ERβ, as well as aromatase, the enzyme responsible for the conversion of testosterone to estradiol, and possibly other steroid hormone receptors. Third, experimental studies indicate that glioblastomas transplanted into animals grow at a slower rate in females compared with males. Finally, experimental studies show that estradiol, 2-methoxyestradiol, and a number of selective estrogen receptor modulators inhibit proliferation of gliomas and induce cell death. These hormonal agonists and antagonists may act either through classical steroid hormone receptors or independently of such receptors. In view of these findings, further clinical, experimental, and epidemiologic studies are needed to elucidate the role of steroid hormone agonists and antagonists in the development and proliferation of glioma. If hormonal pathways are involved in gliomagenesis, this could eventually lead to the design of preventive strategies. Cancer Epidemiol Biomarkers Prev; 19(10); 2421-7. ©2010 AACR.Little is known about the etiology of brain neoplasms, which in general are highly fatal (1). Gliomas, which include astrocytomas, oligodendrogliomas, and ependymomas, are the most common type of primary malignant brain tumor, accounting for approximately 80% of cases (2). Gliomas originate from glial cells (astrocytes or oligodendrocytes). Gliobastoma multiforme, the highest grade of glioma, is the most common and most aggressive type of malignant glioma. Most cases of glioblastoma multiforme (∼90%), referred to as "primary glioblastoma multiforme," develop rapidly without detectable evidence of a less malignant precursor tumor, whereas about 10% of glioblastomas, referred to as "secondary glioblastoma multiforme," develop slowly from low-grade astrocytomas (3). The only established risk factors for gliomas are high-dose ionizing radiation and certain rare genetic conditions, which together account for only a small proportion of cases (1, 4, 5). However, evidence from a number of sources suggests a possible role of endogenous ovarian steroid hormones in the development of glioma. Given that this topic has received little attention in major reviews on brain tumor epidemiology to date (1, 4-6), we review here findings from descriptive and analytic epidemiology, clinical studies, and experimental animal and cell culture studies pertinent to the potential role of steroid hormones in the development of glioma. Descriptive EpidemiologyThe incidence rate of glioma in adulthood is 50% greater in men than in women (5, 7). For example...

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