Faculty Collaboration Database

SWI/SNF gene variants and glioma risk and outcome. Cancer Epidemiol 2013 Apr;37(2):162-5

Date

01/02/2013

Pubmed ID

23276717

Pubmed Central ID

PMC3578123

DOI

10.1016/j.canep.2012.12.001

Scopus ID

2-s2.0-84875809254 (requires institutional sign-in at Scopus site)   12 Citations

Abstract

BACKGROUND: The human SWItch/Sucrose Non-Fermentable (SWI/SNF) chromatin remodeling complex plays essential roles in a variety of cellular processes and has been implicated in human cancer. However, the role of germline genetic variants in this complex in relation to cancer risk is not well studied.

METHODS: We assessed the association of 16 variants in the catalytic subunits (SMARCA2 and SMARCA4) of the SWI/SNF complex with the risk of glioma subtypes (lower grade astrocytoma, oligodendroglioma and glioblastoma [GBM]) and with mortality from high-grade tumors (GBM) in a multicenter US case-control study that included 561 cases and 574 controls. Associations were estimated with odds ratios (OR, for risk) or hazards ratios (HR, for mortality) with 95% confidence intervals (CI). False discovery rate (FDR-q) was used to control for multiple testing in risk associations.

RESULTS: None of the investigated SNPs was associated with overall glioma risk. However, analyses according to histological subtypes revealed a statistically significant increased risk of oligodendroglioma in association with SMARCA2 rs2296212 (OR = 4.05, 95% CI = 1.11-14.80, P = 0.030, q = 0.08) and rs4741651 (OR = 4.68, 95% CI = 1.43-15.30, P = 0.011, q = 0.08) and SMARCA4 rs11672232 (OR = 1.90, 95% CI = 1.01-3.58, P = 0.048, q = 0.08) and rs12232780 (OR = 2.14, 95% CI = 1.06-4.33, P = 0.035, q = 0.08). No significant risk associations were observed for GBM or lower grade astrocytoma. Suggestive associations with GBM mortality were not validated in the Cancer Genome Atlas.

CONCLUSION: Our findings suggest that genetic variants in SMARCA2 and SMARCA4 influence the risk of oligodendroglioma. Further research is warranted on the SWI/SNF complex genes and epigenetic mechanisms more generally in the development of glioma in adults.

Author List

Amankwah EK, Thompson RC, Nabors LB, Olson JJ, Browning JE, Madden MH, Egan KM

Author

Ernest Amankwah PhD Director, Associate Professor in the Clinical and Translational Science Institute department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Aged, 80 and over
Brain Neoplasms
Case-Control Studies
DNA Helicases
Female
Follow-Up Studies
Genome-Wide Association Study
Glioma
Humans
Male
Middle Aged
Neoplasm Grading
Nuclear Proteins
Oligodendroglioma
Polymorphism, Single Nucleotide
Prognosis
Risk Factors
Survival Rate
Transcription Factors
Young Adult