SWI/SNF gene variants and glioma risk and outcome

Ernest K. Amankwah; Reid C. Thompson; L. Burton Nabors; Jeffrey J. Olson; James E. Browning; Melissa H. Madden; Kathleen M. Egan

doi:10.1016/j.canep.2012.12.001

SWI/SNF gene variants and glioma risk and outcome

Ernest K. Amankwah, Reid C. Thompson, L. Burton Nabors, Jeffrey J. Olson, James E. Browning, Melissa H. Madden, Kathleen M. Egan

Research output: Contribution to journal › Article › peer-review

10 Scopus 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.

Original language	English (US)
Pages (from-to)	162-165
Number of pages	4
Journal	Cancer Epidemiology
Volume	37
Issue number	2
DOIs	https://doi.org/10.1016/j.canep.2012.12.001
State	Published - Apr 2013
Externally published	Yes

Keywords

Chromatin remodeling
Glioma
SMARCA2
SMARCA4
SNP
SWI/SNF

ASJC Scopus subject areas

Epidemiology
Oncology
Cancer Research

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10.1016/j.canep.2012.12.001

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@article{bff3dbfb5d42439abc7e04d275c532f3,

title = "SWI/SNF gene variants and glioma risk and outcome",

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.",

keywords = "Chromatin remodeling, Glioma, SMARCA2, SMARCA4, SNP, SWI/SNF",

author = "Amankwah, {Ernest K.} and Thompson, {Reid C.} and Nabors, {L. Burton} and Olson, {Jeffrey J.} and Browning, {James E.} and Madden, {Melissa H.} and Egan, {Kathleen M.}",

note = "Funding Information: The development of this manuscript was supported in part by a cancer prevention fellowship for EKA by the National Cancer Institute Grant R25T CA147832 . The parent study is supported by Public Health Service Grants R01CA116174 from the National Cancer Institute, National Institutes of Health , and institutional funding from the Moffitt Cancer Center, Tampa, FL and the Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN . The results published here are in part based upon data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI ( http://cancergenome.nih.gov/ ). Study Accession:phs000178.v5.p5.",

year = "2013",

month = apr,

doi = "10.1016/j.canep.2012.12.001",

language = "English (US)",

volume = "37",

pages = "162--165",

journal = "Cancer Epidemiology",

issn = "1877-7821",

publisher = "Elsevier BV",

number = "2",

}

TY - JOUR

T1 - SWI/SNF gene variants and glioma risk and outcome

AU - Amankwah, Ernest K.

AU - Thompson, Reid C.

AU - Nabors, L. Burton

AU - Olson, Jeffrey J.

AU - Browning, James E.

AU - Madden, Melissa H.

AU - Egan, Kathleen M.

N1 - Funding Information: The development of this manuscript was supported in part by a cancer prevention fellowship for EKA by the National Cancer Institute Grant R25T CA147832 . The parent study is supported by Public Health Service Grants R01CA116174 from the National Cancer Institute, National Institutes of Health , and institutional funding from the Moffitt Cancer Center, Tampa, FL and the Vanderbilt-Ingram Comprehensive Cancer Center, Nashville, TN . The results published here are in part based upon data generated by The Cancer Genome Atlas pilot project established by the NCI and NHGRI ( http://cancergenome.nih.gov/ ). Study Accession:phs000178.v5.p5.

PY - 2013/4

Y1 - 2013/4

N2 - 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.

AB - 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.

KW - Chromatin remodeling

KW - Glioma

KW - SMARCA2

KW - SMARCA4

KW - SNP

KW - SWI/SNF

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U2 - 10.1016/j.canep.2012.12.001

DO - 10.1016/j.canep.2012.12.001

M3 - Article

C2 - 23276717

AN - SCOPUS:84875809254

SN - 1877-7821

VL - 37

SP - 162

EP - 165

JO - Cancer Epidemiology

JF - Cancer Epidemiology

IS - 2

ER -

SWI/SNF gene variants and glioma risk and outcome

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Keywords

ASJC Scopus subject areas

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