title: Understanding inherited genetic risk of adult glioma - a review.
abstract: During the past six years, researchers have made major progress identifying common inherited genetic variation that increases risk for primary adult glioma. This paper summarizes knowledge about rare familial cancer syndromes that include adult glioma and reviews the available literature on the more recently discovered common inherited variation. Ten independent inherited variants in eight chromosomal regions have been convincingly associated with increased risk for adult glioma. Most of these variants increase relative risk of primary adult glioma by 20% to 40%, but the TP53 variant rs78378222 confers a two-fold relative risk (ie, 200%), and rs557505857 on chromosome 8 confers a six-fold relative risk ofIDH-mutated astrocytomas and oligodendroglial tumors (ie, 600%). Even with a six-fold relative risk, the overall risk of developing adult glioma is too low for screening for the high-risk variant on chromosome 8. Future studies will help clarify which inherited adult glioma risk variants are associated with subtypes defined by histology and/or acquired tumor mutations. This review also provides an information sheet for primary adult glioma patients and their families.
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Terri
authors.initials: T
authors.lastname: Rice
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Lachance
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Annette M
authors.initials: AM
authors.lastname: Molinaro
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Jeanette E
authors.initials: JE
authors.lastname: Eckel-Passow
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Walsh
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Jill
authors.initials: J
authors.lastname: Barnholtz-Sloan
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Quinn T
authors.initials: QT
authors.lastname: Ostrom
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Francis
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Joseph
authors.initials: J
authors.lastname: Wiemels
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Robert B
authors.initials: RB
authors.lastname: Jenkins
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: John K
authors.initials: JK
authors.lastname: Wiencke
authors.affiliation: Division of Neuroepidemiology, Department of Neurological Surgery , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (T.R., A.M.M., K.M.W, S.S.F., J.W., J.K.W., M.R.W.); Department of Laboratory Medicine and Pathology , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (D.H.L., R.B.J.); Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905 (D.H.L.) ; Department of Epidemiology and Biostatistics , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (A.M.M., J.W.); Division of Biomedical Statistics and Informatics , Mayo Clinic College of Medicine , 200 First Street SW, Rochester, MN 55905 (J.E.E.-P.); Program in Cancer Genetics, Helen Diller Family Comprehensive Cancer Center , University of California , San Francisco, 1450 3rd Street, San Francisco, CA 94158 (K.M.W., J.W., J.K.W., M.R.W.); Case Comprehensive Cancer Center , Case Western Reserve University School of Medicine , 11100 Euclid Avenue, Cleveland, OH 44106-5065 (J.B.-S., Q.T.O.); Central Brain Tumor Registry of the United States , 244 East Ogden Ave Suite 116, Hinsdale, IL 60521 (J.B.-S., Q.T.O.).
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Wrensch
keywords: epidemiology; genetics; primary adult glioma; risk; variants