Common genetic variants related to genomic integrity and risk of papillary thyroid cancer

Gila Neta; Alina V. Brenner; Erich M. Sturgis; Ruth M. Pfeiffer; Amy A. Hutchinson; Briseis Aschebrook-Kilfoy; Meredith Yeager; Li Xu; William Wheeler; Michael Abend; Elaine Ron; Margaret A. Tucker; Stephen J. Chanock; Alice J. Sigurdson

doi:10.1093/carcin/bgr100

Common genetic variants related to genomic integrity and risk of papillary thyroid cancer

Gila Neta, Alina V. Brenner, Erich M. Sturgis, Ruth M. Pfeiffer, Amy A. Hutchinson, Briseis Aschebrook-Kilfoy, Meredith Yeager, Li Xu, William Wheeler, Michael Abend, Elaine Ron, Margaret A. Tucker, Stephen J. Chanock, Alice J. Sigurdson

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Abstract

DNA damage is an important mechanism in carcinogenesis, so genes related to maintaining genomic integrity may influence papillary thyroid cancer (PTC) risk. Candidate gene studies targeting some of these genes have identified only a few polymorphisms associated with risk of PTC. Here, we expanded the scope of previous candidate studies by increasing the number and coverage of genes related to maintenance of genomic integrity. We evaluated 5077 tag single-nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function and cell cycle control and signaling pathways in a case-control study of 344 PTC cases and 452 matched controls. We estimated odds ratios for associations of single SNPs with PTC risk and combined P values for SNPs in the same gene region or pathway to obtain gene region-specific or pathway-specific P values using adaptive rank-truncated product methods. Nine SNPs had P values <0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P < 0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3 and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC. Published by Oxford University Press 2011.

Original language	English (US)
Pages (from-to)	1231-1237
Number of pages	7
Journal	Carcinogenesis
Volume	32
Issue number	8
DOIs	https://doi.org/10.1093/carcin/bgr100
State	Published - Aug 2011

ASJC Scopus subject areas

Cancer Research

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Neta, G., Brenner, A. V., Sturgis, E. M., Pfeiffer, R. M., Hutchinson, A. A., Aschebrook-Kilfoy, B., Yeager, M., Xu, L., Wheeler, W., Abend, M., Ron, E., Tucker, M. A., Chanock, S. J., & Sigurdson, A. J. (2011). Common genetic variants related to genomic integrity and risk of papillary thyroid cancer. Carcinogenesis, 32(8), 1231-1237. https://doi.org/10.1093/carcin/bgr100

@article{f03af005e4454731bee26bb3747e43fc,

title = "Common genetic variants related to genomic integrity and risk of papillary thyroid cancer",

abstract = "DNA damage is an important mechanism in carcinogenesis, so genes related to maintaining genomic integrity may influence papillary thyroid cancer (PTC) risk. Candidate gene studies targeting some of these genes have identified only a few polymorphisms associated with risk of PTC. Here, we expanded the scope of previous candidate studies by increasing the number and coverage of genes related to maintenance of genomic integrity. We evaluated 5077 tag single-nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function and cell cycle control and signaling pathways in a case-control study of 344 PTC cases and 452 matched controls. We estimated odds ratios for associations of single SNPs with PTC risk and combined P values for SNPs in the same gene region or pathway to obtain gene region-specific or pathway-specific P values using adaptive rank-truncated product methods. Nine SNPs had P values <0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P < 0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3 and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC. Published by Oxford University Press 2011.",

author = "Gila Neta and Brenner, {Alina V.} and Sturgis, {Erich M.} and Pfeiffer, {Ruth M.} and Hutchinson, {Amy A.} and Briseis Aschebrook-Kilfoy and Meredith Yeager and Li Xu and William Wheeler and Michael Abend and Elaine Ron and Tucker, {Margaret A.} and Chanock, {Stephen J.} and Sigurdson, {Alice J.}",

note = "Funding Information: This research was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health and by a grant from the American Thyroid Association (Principal Investigator: E.M.S.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E.",

year = "2011",

month = aug,

doi = "10.1093/carcin/bgr100",

language = "English (US)",

volume = "32",

pages = "1231--1237",

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T1 - Common genetic variants related to genomic integrity and risk of papillary thyroid cancer

AU - Neta, Gila

AU - Brenner, Alina V.

AU - Sturgis, Erich M.

AU - Pfeiffer, Ruth M.

AU - Hutchinson, Amy A.

AU - Aschebrook-Kilfoy, Briseis

AU - Yeager, Meredith

AU - Xu, Li

AU - Wheeler, William

AU - Abend, Michael

AU - Ron, Elaine

AU - Tucker, Margaret A.

AU - Chanock, Stephen J.

AU - Sigurdson, Alice J.

N1 - Funding Information: This research was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health and by a grant from the American Thyroid Association (Principal Investigator: E.M.S.). This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract number HHSN261200800001E.

PY - 2011/8

Y1 - 2011/8

N2 - DNA damage is an important mechanism in carcinogenesis, so genes related to maintaining genomic integrity may influence papillary thyroid cancer (PTC) risk. Candidate gene studies targeting some of these genes have identified only a few polymorphisms associated with risk of PTC. Here, we expanded the scope of previous candidate studies by increasing the number and coverage of genes related to maintenance of genomic integrity. We evaluated 5077 tag single-nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function and cell cycle control and signaling pathways in a case-control study of 344 PTC cases and 452 matched controls. We estimated odds ratios for associations of single SNPs with PTC risk and combined P values for SNPs in the same gene region or pathway to obtain gene region-specific or pathway-specific P values using adaptive rank-truncated product methods. Nine SNPs had P values <0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P < 0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3 and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC. Published by Oxford University Press 2011.

AB - DNA damage is an important mechanism in carcinogenesis, so genes related to maintaining genomic integrity may influence papillary thyroid cancer (PTC) risk. Candidate gene studies targeting some of these genes have identified only a few polymorphisms associated with risk of PTC. Here, we expanded the scope of previous candidate studies by increasing the number and coverage of genes related to maintenance of genomic integrity. We evaluated 5077 tag single-nucleotide polymorphisms (SNPs) from 340 candidate gene regions hypothesized to be involved in DNA repair, epigenetics, tumor suppression, apoptosis, telomere function and cell cycle control and signaling pathways in a case-control study of 344 PTC cases and 452 matched controls. We estimated odds ratios for associations of single SNPs with PTC risk and combined P values for SNPs in the same gene region or pathway to obtain gene region-specific or pathway-specific P values using adaptive rank-truncated product methods. Nine SNPs had P values <0.0005, three of which were in HDAC4 and were inversely related to PTC risk. After multiple comparisons adjustment, no SNPs remained associated with PTC risk. Seven gene regions were associated with PTC risk at P < 0.01, including HUS1, ALKBH3, HDAC4, BAK1, FAF1_CDKN2C, DACT3 and FZD6. Our results suggest a possible role of genes involved in maintenance of genomic integrity in relation to risk of PTC. Published by Oxford University Press 2011.

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DO - 10.1093/carcin/bgr100

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AN - SCOPUS:79961203606

SN - 0143-3334

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SP - 1231

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JO - Carcinogenesis

JF - Carcinogenesis

IS - 8

ER -

Common genetic variants related to genomic integrity and risk of papillary thyroid cancer

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