Genetic variation in insulin-like growth factors and brain tumor risk

¹ Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
² Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
³ Division of Neuro-oncology Branch, National Cancer Institute, Bethesda, MD, USA
⁴ Western Pennsylvania Hospital, Pittsburgh, PA, USA
⁵ Brigham and Women's Hospital, Boston, MA, USA
⁶ Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA, USA
⁷ Division of Cancer Epidemiology and Genetics, Core Genotyping Facility, Advanced Technology Center, SAIC-Frederick, Inc., National Cancer Institute-Frederick, Frederick, MD, USA

^* To whom correspondence should be addressed. E-mail: Stefan.Lonn{at}ki.se.

	Abstract

Many studies support a role for insulin-like growth factors (IGFs) in the regulation of tumor cell biology. We hypothesized that single-nucleotide polymorphisms (SNPs) in IGF genes are risk factors for glioma and meningioma. To test the hypothesis, we examined associations of brain tumor risk with nine variants in five IGF genes in a hospital-based case-control study. The study was conducted at hospitals in Boston, Phoenix, and Pittsburgh between 1994 and 1998. Eligible cases were individuals (18 years or older) newly diagnosed with glioma or meningioma. Controls were selected among patients who were admitted to the same hospitals for a variety of nonmalignant conditions and frequency matched to cases by hospital, age, sex, race, and distance from residence. The present analysis was restricted to non-Hispanic whites. DNA was extracted from blood samples collected from 354 glioma cases, 133 meningioma cases, and 495 control individuals. We evaluated nine SNPs in five IGF genes (IGF1, IGF1R, IGF2, IGF2R, and IGFBP3). The majority of the analyzed IGF SNPs did not display statistically significant associations with glioma or meningioma. For glioma, one IGF1R SNP (rs2272037) indicated a possible association. No indications of association were seen for glioblastoma, but for low-grade gliomas, the odds ratio under a dominant model was 0.56 (95% confidence interval [CI], 0.35-0.90) for IGF1 rs6220, 2.98 (95% CI, 1.65-5.38) for IGF1R rs2272037, and 1.60 (95% CI, 0.90-2.83) for IGF1R rs2016347. Overall, our results do not provide strong evidence of associations of brain tumor risk with IGF polymorphic variants but identify several associations for glioma that warrant further examination in other, larger studies.

Key Words: central nervous system, glioma, insulin-like growth factor, meningioma, single nucleotide polymorphism

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