Reproductive factors and risk of glioma in women

Department of Mathematical Sciences, University of Cincinnati, Cincinnati, Ohio, United States
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 10/2004; 13(10):1583-8.
Source: PubMed


Glioma is the most common primary malignant brain tumor in adults, responsible for 75% of adult primary malignant brain tumors, yet aside from its association with ionizing radiation, its etiology is poorly understood. Sex differences in brain tumor incidence suggest that hormonal factors may play a role in the etiology of these tumors, but few studies have examined this association in detail. The objective of this study was to explore the role of reproductive factors in the etiology of glioma in women.
As part of a population-based case-control study, histologically confirmed primary glioma cases (n = 341 women) diagnosed between January 1, 1995 and January 31, 1997 were identified through clinics and hospitals in four Midwest U.S. states. Controls (n = 527 women) were randomly selected from lists of licensed drivers and Health Care Finance Administration enrollees. In-person interviews with subjects (81%) or their proxies (19%) collected reproductive history and other exposure information.
Glioma risk increased with older age at menarche (P for trend = 0.009) but only among postmenopausal women. Compared with women who never breast-fed, women who breast-fed >18 months over their lifetime were at increased risk of glioma (odds ratio, 1.8; 95% confidence interval, 1.1-2.9). Women who reported using hormones for symptoms of menopause had a decreased risk of glioma compared with women who never used such hormones (odds ratio, 0.7; 95% confidence interval, 0.5-1.1).
These results support the hypothesis that reproductive hormones play a role in the etiology of glioma among women.

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Available from: James A Deddens, Jan 23, 2015
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    • "Menopausal status , steroid hormones use . Huang , 2004 USA 1995 – 1997 18 – 80 PCC 341 / 527 Yes In - person interview OC , HRT , Age at menarche , first birth and last birth , Number of live births , Breast Feeding , Menstruation months , Type of menopause . Hatch , 2005 USA 1994 – 1998 $ 15 HCC 212 / 436 Yes Questionnaire or in - person interview Age at menarche , first birth , and menopause , Ever pregnant , Ever had live birth , Number of live birth , Menopausal status , Type of menopause , Breast Feeding , Bilateral oophorectomy . "
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    ABSTRACT: Previous investigations of glioma risk in women have focused on oral contraceptive (OC), hormone replacement therapy (HRT), and reproductive factors. However, the results of published studies were inconclusive and inconsistent. Thus, a meta-analysis based on published case-control studies was performed to assess the role of exogenous and endogenous hormones factors in glioma risk. The PubMed and EMBASE databases were searched without any restrictions on language or publication year. Reference lists from retrieved articles were also reviewed. We included case-control studies reporting relative risks (RRs) with corresponding 95% confidence intervals (CIs) (or data to calculate them) between oral contraceptive (OC) and hormone replacement therapy (HRT) use, reproductive factors and glioma. Random-effects models were used to calculate the summary risk estimates. Finally, 11 eligible studies with 4860 cases and 14,740 controls were identified. A lower risk of glioma was observed among women who were ever users of exogenous hormones (OC RR = 0.707, 95% CI = 0.604-0.828; HRT: RR = 0.683, 95% CI = 0.577-0.808) compared with never users. An increased glioma risk was associated with older age at menarche (RR = 1.401, 95% CI = 1.052-1.865). No association was observed for menopause status, parous status, age at menopause, or age at first birth and glioma risk. The results of our study support the hypothesis female sex hormones play a role in the development of glioma in women. Additional studies are warranted to validate the conclusion from this meta-analysis and clarity the underlying mechanisms.
    Preview · Article · Jul 2013 · PLoS ONE
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    • "Other studies, however, have failed to find statistically significant association between the use of OCs and brain cancer [3,4,16,18,19,22]. Regarding HRT, previous studies have largely reported no association between HRT and brain cancer risk [3,4,16-18,22]. We were unable to adjust for these two hormonal factors in the current study due to the lack of available data. Since the use of OC and HRT are low in Taiwan compared with Western countries [38,39], the confounding effect resulting from these two factors should be small, if any exists at all. "
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    ABSTRACT: Background This study was undertaken to examine whether there is an association between parity and age at first birth and risk of death from brain cancer. Methods The study cohort consisted of 1,292,462 women who had a first and singleton childbirth between Jan. 1, 1978 and Dec. 31, 1987. We tracked each woman from the time of their first childbirth to December 31, 2009, and their vital status was ascertained by linking records with the computerized mortality database. Cox proportional hazard regression models were used to estimate the hazard ratios (HR) of death from brain cancer associated with parity and age at first birth. Results There were 316 brain cancer deaths during 34,980,246 person-years of follow-up. The mortality rate of brain cancer was 0.90 cases per 100,000 person-years. The adjusted HR was 1.35 (95% CI= 0.91-2.01) for women who gave birth between 21 and 25, 1.61 (95% CI=1.05-2.45) for women who gave birth after 25 years of age, respectively, when compared with women who gave birth less than 20 years. A trend of increasing risk of brain cancer was seen with increasing age at first birth. The adjusted HR were 0.73 (95% CI= 0.53-0.99) for women who had 2 children, and 0.60 (95% CI =0.43-0.83) for women with 3 or more births, respectively, when compared with women who had given birth to only 1 child. There was a significant decreasing trend in the HRs of brain cancer with increasing parity. Conclusions This study provides evidence that reproductive factors (parity and early age at first birth) may confer a protective effect on the risk of death from brain cancer.
    Full-text · Article · Oct 2012 · BMC Public Health
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    • "Sex hormones play a multifaceted role throughout the body. Sex differences in brain tumour incidence suggest that hormonal factors may play a role in the aetiology of this type of tumour and there is evidence that hormones related to female reproductive function may be associated with brain cancer risk (Huang et al, 2004). The incidence of glioma is 1.5 times greater in men than in women and it has been described an inverse relationship between younger age at menarche (among postmenopausal women), cumulative number of menstrual cycles over the lifetime, fewer months of breast-feeding and the use of hormone-replacement therapy and the risk for glioma (Inskip et al, 1995; Huang et al, 2004). "
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    ABSTRACT: Melatonin exerts oncostatic effects on different kinds of neoplasias, especially on oestrogen-dependent tumours. Recently, it has been described that melatonin, on the basis of its antioxidant properties, inhibits the growth of glioma cells. Glioma cells express oestrogen receptors and have the ability to synthesise oestrogens from androgens. In the present study, we demonstrate that pharmacological concentrations of melatonin decreases the growth of C6 glioma cells and reduces the local biosynthesis of oestrogens, through the inhibition of aromatase, the enzyme that catalyses the conversion of androgens into oestrogens. These results are supported by three types of evidence. Firstly, melatonin counteracts the growth stimulatory effects of testosterone on glioma cells, which is dependent on the local synthesis of oestrogens from testosterone. Secondly, we found that melatonin reduces the aromatase activity of C6 cells, measured by the tritiated water release assay. Finally, by (RT)–PCR, we found that melatonin downregulates aromatase mRNA steady-state levels in these glioma cells. We conclude that melatonin inhibits the local production of oestrogens decreasing aromatase activity and expression. By analogy to the implications of aromatase in other forms of oestrogen-sensitive tumours, it is conceivable that the modulation of the aromatase by pharmacological melatonin may play a role in the growth of glioblastomas.Keywords: melatonin, pineal, glioma cells, C6 cells, aromatase
    Full-text · Article · Aug 2007 · British Journal of Cancer
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