The Common D302H Variant of CASP8 Is Associated with Risk of Glioma
- Lara Bethke1,
- Kate Sullivan1,
- Emily Webb1,
- Anne Murray1,
- Minouk Schoemaker2,
- Anssi Auvinen3,4,
- Anne Kiuru3,
- Tiina Salminen3,4,
- Christoffer Johansen5,
- Helle Collatz Christensen5,
- Kenneth Muir6,
- Patricia McKinney7,
- Sarah Hepworth7,
- Polyxeni Dimitropoulou6,
- Artitaya Lophatananon6,
- Maria Feychting8,
- Stefan Lönn9,
- Anders Ahlbom8,
- Beatrice Malmer10,
- Roger Henriksson10,
- Anthony Swerdlow2 and
- Richard Houlston1
- 1Section of Cancer Genetics and 2Section of Epidemiology, Institute of Cancer Research, Sutton, Surrey, United Kingdom; 3Department of Epidemiology, Tampere School of Public Health, University of Tampere, Tampere, Finland; 4Department of Research and Environmental Surveillance, Radiation and Nuclear Safety Authority, Radiation and Nuclear Safety Authority, Helsinki, Finland; 5Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; 6Division of Epidemiology and Public Health, University of Nottingham Medical School, Queen's Medical Centre, Nottingham, United Kingdom; 7Centre for Epidemiology and Biostatistics, Leeds, United Kingdom; 8Division of Epidemiology, Institute of Environmental Medicine and 9Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; and 10Department of Radiation Sciences, Umeå University, Umeå, Sweden
- Requests for reprints:
Richard Houlston, Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, UK. Phone: 44-0-208-722-4175; Fax: 44-0-208-722-4359. E-mail: richard.houlston{at}icr.ac.uk
Abstract
Caspase 8 (CASP8) is a key regulator of apoptosis or programmed cell death, and, hence, a defense against cancer. We tested the hypothesis that the CASP8 polymorphism D302H influences risk of glioma through analysis of five series of glioma case patients and controls (n = 1,005 and 1,011, respectively). Carrier status for the rare allele of D302H was associated with a 1.37-fold increased risk (95% confidence interval, 1.10-1.70; P = 0.004). The association of CASP8 D302H with glioma risk indicates the importance of inherited variation in the apoptosis pathway in susceptibility to this form of primary brain tumor. (Cancer Epidemiol Biomarkers Prev 2008;17(4):987–9)
Footnotes
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Grant support: Cancer Research UK. The Interphone Study was supported by the European Commission Fifth Framework Program "Quality of Life and Management of Living Resources" (Contract QLK4-CT-1999-01563) and the International Union against Cancer (RCA/01/08). The International Union against Cancer received funds for this study from the Mobile Manufacturers' Forum and the Global System for Mobile Communications Association. Provision of funds to the Interphone study investigators via International Union against Cancer was governed by agreements that guaranteed Interphone's complete scientific independence. These agreements are publicly available at http://www.iarc.fr/ENG/Units/RCAd.html. Additional support was given to the Danish partner by the Danish Cancer Society. The Finnish partner received further financing from the Emil Aaltonen Foundation, The Swedish partner received additional grant funding from the Swedish Research Council, The Swedish Cancer Society, and the Cancer Foundation of Northern Sweden. The United Kingdom Southeast and Northern centers were also supported by the Mobile Telecommunications and Health Research Program and the United Kingdom North by the Health and Safety Executive, Department of Health and Safety Executive, and the United Kingdom Network Operators (O2, Orange, T-Mobile, Vodafone, and ‘3’). The views expressed in the publication are those of the authors and not necessarily those of the funding bodies.
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The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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- Accepted January 22, 2008.
- Received November 16, 2007.
- Revision received January 17, 2008.
