Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping

F. J. Hosking; D. Feldman; R. Bruchim; B. Olver; A. Lloyd; J. Vijayakrishnan; P. Flint-Richter; P. Broderick; R. S. Houlston; S. Sadetzki

doi:10.1038/bjc.2011.61

Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping

F. J. Hosking, D. Feldman, R. Bruchim, B. Olver, A. Lloyd, J. Vijayakrishnan, P. Flint-Richter, P. Broderick, R. S. Houlston, S. Sadetzki^*

^*Corresponding author for this work

School of Public Health

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

Abstract

Background:Exposure to ionising radiation is a well-established risk factor for multiple types of tumours, including malignant brain tumours. In the 1950s, radiotherapy was used to treat Tinea Capitis (TC) in thousands of children, mostly of North-African and Middle Eastern origin, during the mass migration to Israel. The over-representation of radiation-associated meningioma (RAM) and other cancers in specific families provide support for inherited genetic susceptibility to radiation-induced cancer.Methods:To test this hypothesis, we genotyped 15 families segregating RAM using high-density single-nucleotide polymorphism (SNP) arrays. Using the family-based association test (FBAT) programme, we tested each polymorphism and haplotype for an association with RAM.Results:The strongest haplotype associations were attained at 18q21.1 (P7.5 × 10^-5), 18q21.31 (P2.8 × 10^-5) and 10q21.3 (P1.6 × 10^-4). Although associations were not formally statistically significant after adjustment for multiple testing, the 18q21.1 and 10q21.3 associations provide support for a variation in PIAS2, KATNAL2, TCEB3C, TCEB3CL and CTNNA3 genes as risk factors for RAM.Conclusion:These findings suggest that any underlying genetic susceptibility to RAM is likely to be mediated through the co-inheritance of multiple risk alleles rather than a single major gene locus determining radiosensitivity.

Original language	English
Pages (from-to)	1049-1054
Number of pages	6
Journal	British Journal of Cancer
Volume	104
Issue number	6
DOIs	https://doi.org/10.1038/bjc.2011.61
State	Published - 15 Mar 2011

Keywords

genetic
ionising radiation
meningioma
sensitivity

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/bjc.2011.61

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@article{413ef8a9e0654f26adf40c0418759e84,

title = "Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping",

abstract = "Background:Exposure to ionising radiation is a well-established risk factor for multiple types of tumours, including malignant brain tumours. In the 1950s, radiotherapy was used to treat Tinea Capitis (TC) in thousands of children, mostly of North-African and Middle Eastern origin, during the mass migration to Israel. The over-representation of radiation-associated meningioma (RAM) and other cancers in specific families provide support for inherited genetic susceptibility to radiation-induced cancer.Methods:To test this hypothesis, we genotyped 15 families segregating RAM using high-density single-nucleotide polymorphism (SNP) arrays. Using the family-based association test (FBAT) programme, we tested each polymorphism and haplotype for an association with RAM.Results:The strongest haplotype associations were attained at 18q21.1 (P7.5 × 10-5), 18q21.31 (P2.8 × 10-5) and 10q21.3 (P1.6 × 10-4). Although associations were not formally statistically significant after adjustment for multiple testing, the 18q21.1 and 10q21.3 associations provide support for a variation in PIAS2, KATNAL2, TCEB3C, TCEB3CL and CTNNA3 genes as risk factors for RAM.Conclusion:These findings suggest that any underlying genetic susceptibility to RAM is likely to be mediated through the co-inheritance of multiple risk alleles rather than a single major gene locus determining radiosensitivity.",

keywords = "genetic, ionising radiation, meningioma, sensitivity",

author = "Hosking, {F. J.} and D. Feldman and R. Bruchim and B. Olver and A. Lloyd and J. Vijayakrishnan and P. Flint-Richter and P. Broderick and Houlston, {R. S.} and S. Sadetzki",

note = "Funding Information: We thank all individuals who participated in this study. Work at the Institute of Cancer Research was supported by grants from Cancer Research UK (C1298/A8780 and C1298/A8362).",

year = "2011",

month = mar,

day = "15",

doi = "10.1038/bjc.2011.61",

language = "אנגלית",

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T1 - Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping

AU - Hosking, F. J.

AU - Feldman, D.

AU - Bruchim, R.

AU - Olver, B.

AU - Lloyd, A.

AU - Vijayakrishnan, J.

AU - Flint-Richter, P.

AU - Broderick, P.

AU - Houlston, R. S.

AU - Sadetzki, S.

N1 - Funding Information: We thank all individuals who participated in this study. Work at the Institute of Cancer Research was supported by grants from Cancer Research UK (C1298/A8780 and C1298/A8362).

PY - 2011/3/15

Y1 - 2011/3/15

N2 - Background:Exposure to ionising radiation is a well-established risk factor for multiple types of tumours, including malignant brain tumours. In the 1950s, radiotherapy was used to treat Tinea Capitis (TC) in thousands of children, mostly of North-African and Middle Eastern origin, during the mass migration to Israel. The over-representation of radiation-associated meningioma (RAM) and other cancers in specific families provide support for inherited genetic susceptibility to radiation-induced cancer.Methods:To test this hypothesis, we genotyped 15 families segregating RAM using high-density single-nucleotide polymorphism (SNP) arrays. Using the family-based association test (FBAT) programme, we tested each polymorphism and haplotype for an association with RAM.Results:The strongest haplotype associations were attained at 18q21.1 (P7.5 × 10-5), 18q21.31 (P2.8 × 10-5) and 10q21.3 (P1.6 × 10-4). Although associations were not formally statistically significant after adjustment for multiple testing, the 18q21.1 and 10q21.3 associations provide support for a variation in PIAS2, KATNAL2, TCEB3C, TCEB3CL and CTNNA3 genes as risk factors for RAM.Conclusion:These findings suggest that any underlying genetic susceptibility to RAM is likely to be mediated through the co-inheritance of multiple risk alleles rather than a single major gene locus determining radiosensitivity.

AB - Background:Exposure to ionising radiation is a well-established risk factor for multiple types of tumours, including malignant brain tumours. In the 1950s, radiotherapy was used to treat Tinea Capitis (TC) in thousands of children, mostly of North-African and Middle Eastern origin, during the mass migration to Israel. The over-representation of radiation-associated meningioma (RAM) and other cancers in specific families provide support for inherited genetic susceptibility to radiation-induced cancer.Methods:To test this hypothesis, we genotyped 15 families segregating RAM using high-density single-nucleotide polymorphism (SNP) arrays. Using the family-based association test (FBAT) programme, we tested each polymorphism and haplotype for an association with RAM.Results:The strongest haplotype associations were attained at 18q21.1 (P7.5 × 10-5), 18q21.31 (P2.8 × 10-5) and 10q21.3 (P1.6 × 10-4). Although associations were not formally statistically significant after adjustment for multiple testing, the 18q21.1 and 10q21.3 associations provide support for a variation in PIAS2, KATNAL2, TCEB3C, TCEB3CL and CTNNA3 genes as risk factors for RAM.Conclusion:These findings suggest that any underlying genetic susceptibility to RAM is likely to be mediated through the co-inheritance of multiple risk alleles rather than a single major gene locus determining radiosensitivity.

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KW - meningioma

KW - sensitivity

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JF - British Journal of Cancer

IS - 6

ER -

Search for inherited susceptibility to radiation-associated meningioma by genomewide SNP linkage disequilibrium mapping

Abstract

Keywords

UN SDGs

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