GSTP1 polymorphisms sex-specific association with verbal intelligence in survivors of pediatric medulloblastoma tumors

ABSTRACT

Glutathione S-transferase (GST) single nucleotide polymorphisms (SNPs) have been associated with a lower intellectual quotient (IQ) in medulloblastoma survivors. We investigated the association of GSTP1 polymorphisms with intellectual, neurocognitive skills (e.g., attention span, working memory, and processing speed), and adaptive outcomes for long-term pediatric medulloblastoma survivors. We hypothesized that genetic risk and sex-specific risk would contribute to significantly lower performances across all measures. Eighteen long-term pediatric medulloblastoma survivors completed the Wechsler Abbreviated Scale Intelligence, California Verbal Learning Test-II, Auditory Consonant Trigrams, and Oral Symbol Digit Modality Test. Informants were interviewed with the Scales of Independent Behavior-Revised (SIB-R). After controlling for the false discovery rate, females with a polymorphism performed significantly worse than females without a polymorphism on verbal IQ (p = .005) and SIB-R (p = .012). There was a significant interaction between sex and polymorphism status for verbal IQ (b = −1.8, SE = 0.827, CI: −3.58, −.036). The main effect of this interaction was significant for females (p = .004) and not for males (p = .557). We found large effect sizes between males with the polymorphism and females with the polymorphism across measures of attention span (g = .877), working memory (g = 1.12), and processing speed (g = 1.53). Female medulloblastoma survivors with a GSTP1 polymorphism may have increased vulnerability to deficits in core cognitive skills, IQ, and everyday functional outcomes. Sex-specific genetic risk contributes to the variability in long-term verbal intelligence for medulloblastoma survivors.

KEYWORDS:

• Medulloblastoma survivors
• Single-nucleotide polymorphism
• GSTP1
• Neurocognitive outcomes
• Adaptive functioning

Acknowledgments

We are indebted to the participants of this study, who gave willingly of their time and effort to make this research possible. This research was supported by an Aflac Cancer & Blood Disorders Center Pediatric Hematology-Oncology Research Grant (TZK & TM), a Research Scholar Grant from the American Cancer Society (TZK, #RSGPB-CPPB-114044), and the Second Century Initiative Neurogenomics Fellowship program (RK).

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the American Cancer Society [Research Scholar Grant/RSGPB-CPPB-114044];Georgia State University [Second Century Initiative Neurogenomics Fellowship];AFLAC Cancer & Blood Disorders Center [Pediatric Hematology-Oncology Research Grant].