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Polymorphisms Associated with Asthma Are Inversely Related to Glioblastoma Multiforme

¹ Division of Epidemiology and Biometrics, School of Public Health; ² Comprehensive Cancer Center and ³ Department of Statistics; Ohio State University, Columbus, Ohio; ⁴ Division of Epidemiology, Institute for Environmental Medicine, Karolinska Institutet, Stockholm; ⁵ Department of Radiation Sciences, Oncology, Umeå University Hospital, Umeå, Sweden; ⁶ Department of Genetics, University of Leicester, England, United Kingdom; and ⁷ Wake Forest University, School of Medicine, Brain Tumor Center of Excellence, Wake Forest, North Carolina

Requests for reprints: Judith Schwartzbaum, Division of Epidemiology and Biometrics, School of Public Health, Ohio State University, Starling-Loving Hall, 320 West Tenth Avenue, Columbus, OH 43210. Phone: 614-268-1548; Fax: 614-293-3937; E-mail: schwartzbaum.1{at}osu.edu.

A reduced risk of primary malignant adult brain tumors is observed among people reporting asthma, hay fever, and other allergic conditions; however, findings may be attributed to prediagnostic effects of tumors or recall bias. To determine whether asthma and allergic condition polymorphisms are inversely related to glioblastoma multiforme (GBM) risk, we conducted a population-based case-control study of 111 GBM patients and 422 controls. We identified five single nucleotide polymorphisms on three genes previously associated with asthma [interleukin (IL)-4RA, IL-13, ADAM33] and one gene associated with inflammation (cyclooxygenase-2). Confirming previous literature, we found that self-reported asthma, eczema, and fever are inversely related to GBM [e.g., asthma odds ratio (OR), 0.64; 95% confidence interval (CI), 0.33-1.25]. In addition, IL-4RA Ser478Pro TC, CC, and IL-4RA Gln551Arg AG, AA are positively associated with GBM (OR, 1.64; 95% CI, 1.05-2.55; 1.61; 95% CI, 1.05-2.47), whereas IL-13 –1,112 CT, TT is negatively associated with GBM (0.56; 95% CI, 0.33-0.96). Each of these polymorphism-GBM associations is in the opposite direction of a corresponding polymorphism-asthma association, consistent with previous findings that self-reported asthmatics and people with allergic conditions are less likely to have GBM than are people who do not report these conditions. Because we used germ line polymorphisms as biomarkers of susceptibility to asthma and allergic conditions, our results cannot be attributed to recall bias or effects of GBM on the immune system. However, our findings are also consistent with associations between IL-4RA, IL-13, and GBM that are independent of their role in allergic conditions.

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