δ-Aminolevulinic Acid Dehydratase Polymorphism and Risk of Brain Tumors in Adults

TL;DR

This study finds that a genetic variation in the ALAD gene may increase the risk of meningioma, a type of brain tumor, especially in males.

Contribution

The study identifies a potential genetic risk factor for meningioma through the ALAD G177C polymorphism.

Findings

The ALAD2 allele is associated with increased meningioma risk (OR = 1.6) and stronger in males (OR = 3.5).

No association was found between the ALAD2 allele and glioma or acoustic neuroma risk.

The ALAD2 allele may increase genetic susceptibility to meningioma.

Abstract

The enzyme δ -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.