Maternal supplement, micronutrient, and cured meat intake during pregnancy and risk of medulloblastoma during childhood: a children's oncology group study.

We conducted a case-control study of medulloblastoma/primitive neuroectodermal tumors of brain (PNET) to pursue findings related to vitamin and mineral supplements, micronutrients, and cured meat consumption during gestation. Mothers of 315 cases ages <6 years at diagnosis in 1991 to 1997 identified from the United States and Canada through the Children's Oncology Group and mothers of 315 controls selected by random-digit dialing were interviewed. In the periconception period of the index pregnancy, case mothers were less likely than control mothers to report use of multivitamins [adjusted odds ratio (OR), 0.7; 95% confidence interval (95% CI), 0.4-1.0; P = 0.08] and to be in the highest quartile of iron and folate intake from food and supplements combined (adjusted OR for iron, 0.5; 95% CI, 0.3-0.9; P(trend) = 0.008; adjusted OR for folate, 0.5; 95% CI, 0.3-0.9; P(trend) = 0.007). Case and control mothers had similar intakes of cured meats, although case mothers were more likely to have the combination of high cured meat and low vitamin C intake (OR, 1.5; 95% CI, 1.0-2.3; P = 0.08). The results of the study add to the evidence of a protective role for multivitamins, suggest a possible role for micronutrients early in pregnancy, and generally do not support an association between cured meats and medulloblastoma/PNET.

Reovirus prolongs survival and reduces the frequency of spinal and leptomeningeal metastases from medulloblastoma.

Medulloblastoma (MB), the most common pediatric brain tumor, is a highly malignant disease with a 5-year survival rate of only 60%. Tumor cells invade surrounding tissue and disseminate through cerebral spinal fluid, making treatment difficult. Human reovirus type 3 exploits an activated Ras pathway in tumor cells to support productive infection as an oncolytic virus. Here, we examined the ability of human reovirus to kill MB cells lines and surgical specimens in vitro and inhibit tumor growth/metastases in vivo. Most human MB cell lines tested (five of seven = 71.4%), two MB cell lines derived from spontaneously arising tumors in Patched-1(+/-) mice (two of two = 100%) and three MB primary cultures derived from surgical specimens, were susceptible to reovirus infection. Reovirus was internalized and transcribed in both susceptible and resistant cell lines. However, viral protein synthesis was restricted to cell lines with higher levels of activated Ras, suggesting that Ras plays a critical role in reovirus oncolysis in MB. Using an in vivo Daoy orthotopic animal model, we found that a single i.t. injection of reovirus dramatically prolonged survival compared with controls (160 versus 70 days, respectively; P = 0.0003). Repeating this experiment with GFP-labeled Daoy cells and multiple i.t. administrations of reovirus, we again found prolonged survival and a dramatic reduction in spinal and leptomeningeal metastases (66.7% in control injections versus 0.0% in the live virus group). These data suggest that this oncolytic virus may be a potentially effective novel therapy against human MB. Its ability to reduce metastases to the spinal cord could allow a reduction in the dose/field of total neuroaxis cerebral-spinal radiotherapy currently used to treat/prevent cerebral spinal fluid dissemination.

Decline in incidence of medulloblastoma in children.

BACKGROUND: Medulloblastoma is one of the most common intracranial tumors in children. The perception that the incidence of this tumor has declined is reinforced by a decline in enrollment to international trials for the disease. METHODS: A retrospective population-based study of children younger than 15 years whose brain tumors were reviewed histopathologically was performed in the county of Avon, in the southwest region of England from 1976 to 1991. Then, the incidence of medulloblastoma was studied in the noncontiguous southwest and northern regions of England, with a combined childhood population base of 20.0 million child years for the period 1976-1991. RESULTS: In Avon, 16 children with medulloblastoma presented in the period 1976-1984 and 2 in the period 1985-1991, representing a decrease in incidence from 9.6 per million per year to 1.7 per million per year. The incidence of medulloblastoma in the combined southwest and northern regions showed a significant (P = 0.006) decline from 5.5 per million per year in the period 1976-1984 to 2.8 in the period 1985-1991. Considered individually, the decline in the southwest (from 6.2 per million per year to 2.8 per million per year) was significant but that in the Northern region (from 4.7 to 2.7) was not. CONCLUSIONS: In this report, a decline in the incidence of medulloblastoma was shown. In a recent case control study, a protective effect of maternal folate, iron, and multivitamin supplementation against primitive neuroectodermal tumors, including medulloblastoma was found. The introduction of periconceptional multivitamin supplementation in the 1980s may have caused this significant decline in the incidence of medulloblastoma.