Evaluating the association between adult primary brain tumours and a family history of cancer

Abstract

There are very few established causes of primary brain tumours in adults. Associated with short survival times, increasing effort is being put forth in an attempt to better understand the risk factors of these neoplasms, including investigating the possible relationship with a family history of cancer and germline genetic polymorphisms. This thesis was conducted to evaluate both of these potential associations. Using an international population-based case-control study, the self-reported family histories of cancer were compared between 1089 glioma cases and 1922 matched controls and between 307 meningioma cases and 1095 controls. Significantly lowered odds of glioma were associated with the reporting of any type of cancer in a first degree relative (OR = 0.8, 95% CI = 0.7-0.99) and with any type of cancer excluding brain tumours (OR = 0.8, 95% CI = 0.7-0.9). No significant associations were found amongst the meningioma cases and controls, though elevated point estimates were found for those reporting parental lung and genitourinary cancers, while the presence of breast, lip, oral, pharyngeal and unspecified cancers all produced great reductions in meningioma odds, suggesting that further study is required. In order to evaluate the association between adult brain tumours and genetic polymorphisms, a systematic review of the literature was completed. A total of 41 case-control studies were included, covering 46 separate genes and more than 100 different single nucleotide polymorphisms. When possible, quantitative data synthesis was performed to establish a more refined point estimate and confidence intervals. Heterogeneity across the studies and variability in the subject matter often prevented any possible data synthesis so establishing associations that were statistically significant was difficult. All told, there were 41 significant associations found amongst the included studies and each varied by the particular polymorphism or histology studied. None of the estimates produced in the quantitative data syntheses suggested a statistically significant association. The results of this thesis suggest that a family history of cancer is not a risk factor for primary brain tumours in adults and that further work is necessary to better establish the possible association between various genetic polymorphisms and adult brain tumours.