Neurocognitive impairment in relation to glutathione S-transferase enzyme polymorphisms among medulloblastoma patients

Background. Medulloblastoma is a type of brain cancer that accounts for approximately 7-8% of all intracranial tumors and 20-30% of pediatric brain tumors. It is the most common type of malignant brain tumor in childhood. It was reported that majority of survivors with medulloblastoma have social problems, endocrine deficits, and neurological complications. Furthermore, all had significant deficits in neurocognitive functioning. Glutathione S-transferases belong to a family of isoenzymes that catalyze the glutathione conjugation of a variety of electrophilic compounds. Objective. We aimed to determine whether the development of neurocognitive impairment is associated with GST polymorphisms among children and adolescents diagnosed with medulloblastoma (MB) after radiation therapy. Methods. A pilot study composing of 16 children and adolescents diagnosed with MB at Texas Children\u27s Cancer Center was conducted. The t-test was used to determine if the GST polymorphisms were related to neurocognitive impairment and logistic regression was performed to explore association between GST polymorphisms and gender, age at diagnosis, race/ethnicity, and risk group. Results. An association was observed between GSTT1 polymorphism and cognitive impairment one year after radiation and GSTM1 polymorphism two years after radiation. It was observed that patients with GSTT1 null genotype have lower performance IQ (p=0.03) and full scale IQ (p=0.02) one year after radiation and patients with GSTM1 null genotype have lower verbal IQ (p=0.02) two years after radiation. Patients under age 8 have a statistically non-significant higher risk of having not null genotypes compared to those older than age 8 (OR= 7.5, 95%CI: 0.62-90.65 and OR= 2.63, 95%CI: 0.30-23.00 for GSTT1 and GSTM1 respectively). Conclusion. There was a significant association between GSTT1 polymorphism and cognitive impairment one year after radiation and between GSTM1 polymorphism and cognitive impairment two years after radiation. Further large scale studies may be needed to confirm this finding and to examine the underlying mechanism of neurocognitive impairments after treatment of medulloblastoma patients

Evaluating novel risk factors for childhood acute lymphoblastic leukemia

Acute lymphoblastic leukemia (ALL) is the most common childhood leukemia accounting for 70- 75% of cases worldwide. Both genetic and environmental stressors are two major factors suspected to influence the occurrence of ALL. Therapeutic success in survival of childhood ALL has increased the risk of late occurring complications, and co-morbidities. These consequences have a large impact on the quality of a survivor\u27s life and society from continued medical care, ancillary services, and financial burden. In order to reduce the incidence and lessen the burden of childhood ALL, we aim to identify the association of two novel parental occupational exposures, asthmagens and endocrine disrupting chemicals (EDCs), and the risk of childhood ALL among children under the age of 15 years who were recruited at Texas Children\u27s Hospital (TCH), Houston, Texas between May 2007 and April 2012 using job exposure matrices (JEM). In the current study, I studied 129 ALL cases and 212 healthy controls from an ongoing epidemiological case-control study entitled Exploring Potential Risk Factors for Childhood Cancer and Hematological Disorders by Case-Control Studies . Descriptive statistics were used to assess the frequency distribution and differences between case and control parents using chi-squared tests (or Fisher\u27s exact test) for the categorical variables. We believe our findings helped to shed light on the underlying causes and mechanism of the disease, which might help in reducing the incidence of these conditions and the public health burden

Evaluating the role of birth weight and gestational age on acute lymphoblastic leukemia risk among those of Hispanic ethnicity

High birth weight is an established risk factor for childhood acute lymphoblastic leukemia (ALL), especially in children younger than 5 years of age at diagnosis. The goal of this study was to explore the association between being born large for gestational age and the risk for ALL by race/ethnicity to determine if the role of this risk factor differed by these characteristics. The authors compared birth certificate data of 575 children diagnosed with ALL who were younger than 5 years and included in the Texas Cancer Registry, Texas Department of Health, between the years 1995 and 2003 with 11,379 controls matched by birth year. Stratified odds ratios were calculated for risk of ALL by birth weight for gestational age, categorized in 3 groups, small, appropriate, and large for gestational age (SGA, AGA, and LGA, respectively), for each race/ethnicity group. The risk of developing ALL was higher among Hispanics who were LGA (odds ratio [OR] = 1.90, 95% confidence interval [CI]: 1.34-2.68) compared with LGA non-Hispanic whites (OR = 1.27, 95% CI: 0.87-1.86) after adjusting for infant gender, year of birth, maternal age, birth order, and presence of Down syndrome. However, the difference was not statistically significant. These results suggest that there may be differences in the association between higher growth in utero and risk of childhood ALL among Hispanics versus non-Hispanic whites