title: Delta-aminolevulinic acid dehydratase polymorphism and risk of brain tumors in adults.
abstract: The enzyme delta-aminolevulinic acid dehydratase (ALAD), which catalyzes the second step of heme synthesis, can be inhibited by several chemicals, including lead, a potential risk factor for brain tumors, particularly meningioma. In this study we examined whether the ALAD G177C polymorphism in the gene coding for ALAD is associated with risk of intracranial tumors of the brain and nervous system. We use data from a case-control study with 782 incident brain tumor cases and 799 controls frequency matched on hospital, age, sex, race/ethnicity, and residential proximity to the hospital. Blood samples were drawn and DNA subsequently sent for genotyping for 73% of subjects. ALAD genotype was determined for 94% of these samples (355 glioma, 151 meningioma, 67 acoustic neuroma, and 505 controls). Having one or more copy of the ALAD2 allele was associated with increased risk for meningioma [odds ratio (OR) = 1.6; 95% confidence interval (CI), 1.0-2.6], with the association appearing stronger in males (OR = 3.5; 95% CI, 1.3-9.2) than in females (OR = 1.2; 95% CI, 0.7-2.2). No increased risk associated with the ALAD2 variant was observed for glioma or acoustic neuroma. These findings suggest that the ALAD2 allele may increase genetic susceptibility to meningioma.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. rajarama@mail.nih.gov
authors.forename: Preetha
authors.initials: P
authors.lastname: Rajaraman
authors.forename: Brian S
authors.initials: BS
authors.lastname: Schwartz
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Howard A
authors.initials: HA
authors.lastname: Fine
authors.forename: William R
authors.initials: WR
authors.lastname: Shapiro
authors.forename: Robert G
authors.initials: RG
authors.lastname: Selker
authors.forename: Peter M
authors.initials: PM
authors.lastname: Black
authors.forename: Peter D
authors.initials: PD
authors.lastname: Inskip
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001130:Arizona; D001932:Brain Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D004781:Environmental Exposure; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008404:Massachusetts; D008579:Meningioma / Q000453:epidemiology / Q000235:genetics*; D008875:Middle Aged; D010414:Pennsylvania; D011110:Polymorphism, Genetic; D000623:Porphobilinogen Synthase / Q000235:genetics*; D012737:Sex Factors
chemical_list: D000623:Porphobilinogen Synthase