Re: [MNG] recent m research results 37% of all primary brain tumors in europe and inherited risk factors
- Journal of the National Cancer Institute Advance Access originally published online on February 12, 2008
JNCI Journal of the National Cancer Institute 2008 100(4):270-276; doi:10.1093/jnci/djn004
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Articles by Bethke, L.
Articles by Houlston, R.
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Articles by Houlston, R.
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© The Author 2008. Published by Oxford University Press.
Comprehensive Analysis of DNA Repair Gene Variants and Risk of Meningioma
Lara Bethke, Anne Murray, Emily Webb, Minouk Schoemaker, Kenneth Muir, Patricia McKinney, Sarah Hepworth, Polyxeni Dimitropoulou, Artitaya Lophatananon, Maria Feychting, Stefan Lönn, Anders Ahlbom, Beatrice Malmer, Roger Henriksson, Anssi Auvinen, Anne Kiuru, Tiina Salminen, Christoffer Johansen, Helle Collatz Christensen, Michael Kosteljanetz, Anthony Swerdlow, Richard Houlston
Affiliations of authors: Sections of Cancer Genetics (LB, AM, EW, RH) and Epidemiology (MS, AS), Institute of Cancer Research, Sutton, UK; Division of Epidemiology and Public Health, University of Nottingham Medical School Queen’s Medical Centre, Nottingham, UK (KM, PD, AL); Centre for Epidemiology and Biostatistics, University of Leeds, UK (PM, SH); Division of Epidemiology, Institute of Environmental Medicine (MF, A. Ahlbom) and Department of Medical Epidemiology and Biostatistics (SL), Karolinska Institutet, Stockholm, Sweden; Department of Radiation Sciences, Oncology, Umeå University, Sweden (BM, RH); Department of Epidemiology, Tampere School of Public Health, University of Tampere, Finland (A. Auvinen, TS); Department of Research and Environmental Surveillance, Radiation and Nuclear Safety Authority, STUK, Helsinki, Finland (A. Auvinen, AK, TS); Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark (CJ, HCC); Neurosurgical Department, Rigshospitalet, Copenhagen, Denmark (MK)
Correspondence to: Richard Houlston, PhD, Section of Cancer Genetics, Institute of Cancer Research, 15 Cotswold Rd, Sutton, Surrey SM2 5NG, UK (e-mail: richard.houlston@... ).
Background: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility.
Methods: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case–control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided.
Results: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1–interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; Ptrend = 8.95 x 10–6; P = .009 after adjusting for multiple testing).
Conclusions: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.
CONTEXT AND CAVEATS
Meningioma is an uncommon tumor that occurs in the brain, and relatives of meningioma patients have an increased risk of developing the disease. Risk of meningioma is also associated with exposure to ionizing radiation.
Analysis of single-nucleotide polymorphisms (SNPs) in DNA repair genes and their associations with meningioma risk in populations from five case–control studies in northern Europe.
A SNP that is located in the coding portion of the gene for the breast cancer susceptibility gene 1–interacting protein 1 was associated with increased risk for meningioma.
The SNP identified may contribute substantially to meningioma risk because almost 30% of the European population carry the genetic variation.
The study was performed using participants from four countries in Europe who were chosen based on their ethnicity, so how these results may apply to other populations is still unclear. The functional consequence of the genetic variation and how it may contribute to the development of meningioma are unknown.
Manuscript received August 30, 2007; revised December 7, 2007; accepted January 7, 2008.
Sent: Mon, 31 Mar 2008 2:14 pm
Subject: [MNG] recent research radiosurgery results
January 2008, 62:1 > RADIOSURGERY AS DEFINITIVE MANAGEMENT...
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RADIOSURGERY AS DEFINITIVE MANAGEMENT OF INTRACRANIAL MENINGIOMAS.
Neurosurgery. 62(1):53-60, January 2008.
Kondziolka, Douglas M.D., M.Sc.; Mathieu, David M.D.; Lunsford, L. Dade M.D.; Martin, Juan J. M.D.; Madhok, Ricky M.D.; Niranjan, Ajay M.Ch.; Flickinger, John C. M.D.
OBJECTIVE: Stereotactic radiosurgery has become an important primary or adjuvant minimally invasive management strategy for patients with intracranial meningiomas with the goals of long-term tumor growth prevention and maintenance of patient neurological function. We evaluated clinical and imaging outcomes of meningiomas stratified by histological tumor grade.
METHODS: The patient cohort consisted of 972 patients with 1045 intracranial meningiomas managed during an 18-year period. The series included 70% women, 49% of whom had undergone a previous resection and 5% of whom had received previous fractionated radiation therapy. Tumor locations included middle fossa (n = 351), posterior fossa (n = 307), convexity (n = 126), anterior fossa (n = 88), parasagittal region (n = 113), or other (n = 115).
RESULTS: The overall control rate for patients with benign meningiomas (World Health Organization Grade I) was 93%. In those without previous histological confirmation (n = 482), tumor control was 97%. However, for patients with World Health Organization Grade II and III tumors, tumor control was 50 and 17%, respectively. Delayed resection after radiosurgery was necessary in 51 patients (5%) at a mean of 35 months. After 10 years, Grade 1 tumors were controlled in 91% (n = 53); in those without histology, 95% (n = 22) were controlled. None of the patients developed a radiation-induced tumor. The overall morbidity rate was 7.7%. Symptomatic peritumoral imaging changes developed in 4% of the patients at a mean of 8 months.
CONCLUSION: Stereotactic radiosurgery provided high rates of tumor growth control or regression in patients with benign meningiomas with low risk. This study confirms the role of radiosurgery as an effective management choice for patients with small to medium-sized symptomatic, newly diagnosed or recurrent meningiomas of the brain.
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