Genetic epidemiology of childhood brain tumors

Abstract

The study goal was to determine the genetic (heritable) contribution to childhood brain tumors (CBT) which cause nearly one quarter of all childhood cancer deaths. Their etiology remains unknown, but previous studies have suggested a proportion of CBT may be heritable. In this study we collected family histories of 243 confirmed CBT patients referred to The University of Texas M. D. Anderson Cancer Center between the years 1944 and 1983, diagnosed before age 15, and residents of the United States or Canada. Family histories were obtained for all the probands' first degree relatives (parents, siblings, and offspring) and extended to include selected second degree relatives (aunts, uncles, grandparents) using sequential sampling. To determine if these CBT families exhibited excess cancer, we compared their cancer experience to age-, race-, sex-, and calendar-year specific rates from the Connecticut Tumor Registry. No cancer excess was observed among 1,099 first and second degree relatives [39 cancers observed (O) and 44 expected (E) for a standardized incidence ratio (SIR) of 0.88]. For colon cancer, although small numbers, five cases were observed among the probands' first degree relatives with 1.6 expected, for a significant SIR of 3.10. Segregation analysis demonstrated that chance alone could not account for the observed cancer distribution with a multifactorial model providing the best overall explanation of the data. Overall, heredity played a role in the etiology of CBT in 4% of the study families: four (1.7%) due to known hereditary syndromes (nevoid basal cell carcinoma syndrome and von Recklinghausens neurofibromatosis--NF-1), four (1.7%) with multifactorial inheritance, and two additional families with cancers aggregating similar to the clinical criteria described for the Li-Fraumeni cancer family syndrome.

Genetic epidemiology of glioma

“…Since our material is rather small, this could explain the differences between conditional and joint likelihoods. A previous segregation analysis of childhood brain tumours, calculating the segregation for cancer over-all in these families, found that the multifactorial model provided the best fit (Bondy et al, 1991). Given our rather small number of families, this segregation analysis needs to be confirmed in a larger cohort.…”

Cancers in the first-degree relatives of children with brain tumours

“…Childhood brain tumour is represented in many rare cancer syndromes of high risk , but hereditary effects have been ascribed only to some 4% of brain tumours (Bondy et al, 1991). A study on cancer in parents of childhood cancer probands found no increase in the risk of nervous system cancer between the two generations (Olsen et al, 1995); the only parental site that associated with nervous system cancer in offspring was rectal tumour in fathers but not in mothers.…”

“…About 80% of nervous system cancers are brain tumours, the incidence of which is highest in the Nordic countries being about 5 per 100 000 per year in Sweden Hjalmars et al, 1999). In spite of extensive studies, the causes of childhood brain cancer remain elusive, ionizing radiation and genetic predisposition being the only established risk factors (Bondy et al, 1991;Draper et al, 1994;Zahm and Devesa, 1995;Little et al, 1998;Little, 1999;Salminen et al, 1999;Kleihues and Cavenee, 2000). The incidence of brain tumour, particularly in young children (< 5 years) has increased moderately in most industrialized countries from the 1960s to the 1990s (Draper et al, 1994;IARC, 1998;Linet et al, 1999).…”

Breastfeeding and risk of childhood CNS tumours

“…Rare genetic disorders can predispose children to a small proportion of CNS tumours, (Bondy, 1991;Little, 1999) but attempts to identify underlying environmental risk factors have largely been unsuccessful, with only ionising radiation known to confer an increased risk (Linet et al, 2003).…”