Familial factors associated with malignant gliomas

Abstract

Family histories of male patients with histologically confirmed malignant gliomas were compared to family histories of controls (wives). Included were 77 case families with 892 relatives and 77 control families with 719 relatives. Cases had significantly more siblings than controls (P = 0.02), although cases were not preferentially the oldest or the youngest sibs. Odds ratios of two or more were found for mental retardation, Parkinson's disease, and meningitis for the relatives of cases versus controls, but none were statistically significant. The excesses of Parkinson's disease and meningitis were explained by the family of one particularly interesting case containing three relatives with meningitis and two relatives with Parkinson's disease. Noteworthy age-adjusted odds ratios for cancer among relatives of cases compared to relatives of controls were 1.6 (95% confidence interval (CI) = 1.0-2.3) for cancer of any site, 2.4 (95% CI = 0.8-6.1) for breast cancer, and 4.0 (95% CI = 0.6-10.7) for lung cancer. Only the odds ratio for cancer of any site was statistically significant. Overall, 6 of 77 (8%) of cases came from families that included two or more relatives with breast or lung cancer in addition to the proband with malignant glioma. These three cancer sites may form familial clusters worthy of further evaluation in future studies by pedigree and genetic linkage analyses.

Cancer incidence in families with multiple glioma patients

“…As a criterion for accepting a family into the study, at least 2 gliomas per family were required, whereas in most previous studies, families with at least 1 glioma were eligible. [5][6][7][8][9][10][11] In our study, the diluting effect of families with sporadic gliomas is reduced and, therefore, the possibility of detecting cancers associated with hereditary gliomas is increased. The strategy of investigating families with 2 or more gliomas reduces the number of families to be studied but the size of the family is expanded when relatives beyond first-degree are included.…”

“…Although a number of epidemiological studies on glioma families have been reported, association with other types of cancer has remained obscure because earlier results have been inconsistent. [5][6][7][8][9][10][11][12] Therefore, in the present study, the possibility that more than 1 tumour syndrome may involve pedigrees with multiple glioma patients was examined. Unlike most earlier epidemiological studies investigating families with 1 or more gliomas, [5][6][7][8][9][10][11] we focused on families affected with at least 2 verified gliomas.…”

Familial aggregation of astrocytoma in northern Sweden: An epidemiological cohort study

“…Some studies show an increased risk ratio (Choi et al, 1970;Wrensch et al, 1997), but this was not confirmed in other studies (Preston-Martin et al, 1989;Wrensch and Barger, 1990). The findings are inconsistent, and currently no site-specific hereditary or familial astrocytoma has been identified, apart from several case reports of multiple astrocytoma (Kjellin et al, 1960;Ikizler et al, 1992).…”

“…Since most of the FDR were siblings, one explanation could be exposure to the same environmental agents, as suggested by Wrensch and Barger (1990). Another explanation might be that some families are afflicted by a well-known rare inherited syndrome which frequently includes astrocytoma, for example, neurofibromatoses 1 (NF1) (Ilgren et al, 1985), Turcot's disease (Turcot et al, 1959) or the Li-Fraumeni syndrome (Li and Fraumeni, 1969).…”

“…In contrast, a relatively large epidemiological study, including 202 glioma cases found no increased risk for PBT or other cancers (Preston-Martin et al, 1989). Wrensch and Barger (1990) elegantly avoided the problem of recall bias by asking the wives of 77 glioma patients for their family history as well as that of their husbands, thus taking the wives' family history as the control. No increased familial risk for developing brain tumors was observed.…”