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      Why does Jack, and not Jill, break his crown? Sex disparity in brain tumors

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          Abstract

          It is often reported that brain tumors occur more frequently in males, and that males suffer a worse outcome from brain tumors than females. If correct, these observations suggest that sex plays a fundamental role in brain tumor biology. The following review of the literature regarding primary and metastatic brain tumors, reveals that brain tumors do occur more frequently in males compared to females regardless of age, tumor histology, or region of the world. Sexually dimorphic mechanisms that might control tumor cell biology, as well as immune and brain microenvironmental responses to cancer, are explored as the basis for this sex disparity. Elucidating the mechanisms by which sex chromosomes and sex hormones impact on brain tumorigenesis and progression will advance our understanding of basic cancer biology and is likely to be essential for optimizing the care of brain tumor patients.

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          The distribution of secondary growths in cancer of the breast. 1889.

          S. PAGET (1989)
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            Annual Report to the Nation on the Status of Cancer, 1975–2007, Featuring Tumors of the Brain and Other Nervous System

            Betsy Kohler, Elizabeth Ward, Bridget J. McCarthy … (2011)
            Background The American Cancer Society, the Centers for Disease Control and Prevention (CDC), the National Cancer Institute, and the North American Association of Central Cancer Registries (NAACCR) collaborate annually to provide updated information on cancer occurrence and trends in the United States. This year’s report highlights brain and other nervous system (ONS) tumors, including nonmalignant brain tumors, which became reportable on a national level in 2004. Methods Cancer incidence data were obtained from the National Cancer Institute, CDC, and NAACCR, and information on deaths was obtained from the CDC’s National Center for Health Statistics. The annual percentage changes in age-standardized incidence and death rates (2000 US population standard) for all cancers combined and for the top 15 cancers for men and for women were estimated by joinpoint analysis of long-term (1992–2007 for incidence; 1975–2007 for mortality) trends and short-term fixed interval (1998–2007) trends. Analyses of malignant neuroepithelial brain and ONS tumors were based on data from 1980–2007; data on nonmalignant tumors were available for 2004–2007. All statistical tests were two-sided. Results Overall cancer incidence rates decreased by approximately 1% per year; the decrease was statistically significant (P < .05) in women, but not in men, because of a recent increase in prostate cancer incidence. The death rates continued to decrease for both sexes. Childhood cancer incidence rates continued to increase, whereas death rates continued to decrease. Lung cancer death rates decreased in women for the first time during 2003–2007, more than a decade after decreasing in men. During 2004–2007, more than 213 500 primary brain and ONS tumors were diagnosed, and 35.8% were malignant. From 1987–2007, the incidence of neuroepithelial malignant brain and ONS tumors decreased by 0.4% per year in men and women combined. Conclusions The decrease in cancer incidence and mortality reflects progress in cancer prevention, early detection, and treatment. However, major challenges remain, including increasing incidence rates and continued low survival for some cancers. Malignant and nonmalignant brain tumors demonstrate differing patterns of occurrence by sex, age, and race, and exhibit considerable biologic diversity. Inclusion of nonmalignant brain tumors in cancer registries provides a fuller assessment of disease burden and medical resource needs associated with these unique tumors.
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              Altered neural cell fates and medulloblastoma in mouse patched mutants.

              Cynthia M J Higgins, Lisa Goodrich, Lesley E. Scott … (1997)
              The PATCHED (PTC) gene encodes a Sonic hedgehog (Shh) receptor and a tumor suppressor protein that is defective in basal cell nevus syndrome (BCNS). Functions of PTC were investigated by inactivating the mouse gene. Mice homozygous for the ptc mutation died during embryogenesis and were found to have open and overgrown neural tubes. Two Shh target genes, ptc itself and Gli, were derepressed in the ectoderm and mesoderm but not in the endoderm. Shh targets that are, under normal conditions, transcribed ventrally were aberrantly expressed in dorsal and lateral neural tube cells. Thus Ptc appears to be essential for repression of genes that are locally activated by Shh. Mice heterozygous for the ptc mutation were larger than normal, and a subset of them developed hindlimb defects or cerebellar medulloblastomas, abnormalities also seen in BCNS patients.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Biol Sex Differ
                Title: Biology of Sex Differences
                Publisher: BioMed Central
                ISSN (Electronic): 2042-6410
                Publication date Collection: 2012
                Publication date (Electronic): 25 January 2012
                Volume: 3
                Page: 3
                Affiliations
                [1 ]Department of Pediatrics, Division of Pediatric Hematology-Oncology, Washington University School of Medicine, CB 8208, 660 South Euclid Ave, St Louis, MO 63110, USA
                Article
                Publisher ID: 2042-6410-3-3
                DOI: 10.1186/2042-6410-3-3
                PMC ID: 3293746
                PubMed ID: 22277186
                SO-VID: 17b90af9-78a3-4a04-bdf6-2e8246c4b755
                Copyright © Copyright ©2012 Sun et al; licensee BioMed Central Ltd.
                License:

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 25 November 2011
                Date accepted : 25 January 2012
                Categories
                Subject: Review

                ScienceOpen disciplines: Human biology
                Keywords: sex,sexually dimorphic signaling,brain tumors,brain metastases,cytokines
                Data availability:
                ScienceOpen disciplines: Human biology
                Keywords: sex, sexually dimorphic signaling, brain tumors, brain metastases, cytokines

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