Toenail iron, genetic determinants of iron status, and the risk of glioma

Purpose: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of...

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Published in:Cancer causes & control 2013-12, Vol.24 (12), p.2051-2058
Main Authors: Anic, Gabriella M., Madden, Melissa H., Thompson, Reid C., Nabors, L. Burton, Olson, Jeffrey J., LaRocca, Renato V., Browning, James E., Brockman, John D., Forsyth, Peter A., Egan, Kathleen M.
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Biomedical and Life Sciences
Biomedicine
Brain cancer
Brain Neoplasms - blood
Brain Neoplasms - epidemiology
Brain Neoplasms - genetics
Brain research
Cancer
Cancer Research
Case-Control Studies
Dietary iron
DNA damage
DNA, Neoplasm - genetics
Epidemiology
Female
Ferritins - blood
Follow-Up Studies
Genetic testing
Genotype
Genotypes
Glioma
Glioma - blood
Glioma - epidemiology
Glioma - genetics
Hematology
Humans
Iron
Iron - metabolism
Iron, Dietary
Male
Medical genetics
Metabolism
Middle Aged
Nails - chemistry
Neoplasm Grading
Neoplasm Proteins - genetics
Neurosurgery
Oncology
Original Paper
P values
Polymerase Chain Reaction
Prognosis
Public Health
Risk Factors
Survival Rate
Toenails
Tumors
Young Adult
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container_title Cancer causes & control
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creator Anic, Gabriella M.
Madden, Melissa H.
Thompson, Reid C.
Nabors, L. Burton
Olson, Jeffrey J.
LaRocca, Renato V.
Browning, James E.
Brockman, John D.
Forsyth, Peter A.
Egan, Kathleen M.
description Purpose: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case–control study. Methods: Samples were collected a median of 24 days following glioma diagnosis in the cases (10th–90th percentile, range: 10–44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. Results: No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ∼3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 μ/g) vs. low (
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Burton ; Olson, Jeffrey J. ; LaRocca, Renato V. ; Browning, James E. ; Brockman, John D. ; Forsyth, Peter A. ; Egan, Kathleen M.</creator><creatorcontrib>Anic, Gabriella M. ; Madden, Melissa H. ; Thompson, Reid C. ; Nabors, L. Burton ; Olson, Jeffrey J. ; LaRocca, Renato V. ; Browning, James E. ; Brockman, John D. ; Forsyth, Peter A. ; Egan, Kathleen M.</creatorcontrib><description>Purpose: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case–control study. Methods: Samples were collected a median of 24 days following glioma diagnosis in the cases (10th–90th percentile, range: 10–44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. Results: No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ∼3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 μ/g) vs. low (&lt;6 μ/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants. Conclusion: The results do not support a role for body iron stores as a determinant of glioma risk.</description><identifier>ISSN: 0957-5243</identifier><identifier>EISSN: 1573-7225</identifier><identifier>DOI: 10.1007/s10552-013-0281-2</identifier><identifier>PMID: 23996192</identifier><identifier>CODEN: CCCNEN</identifier><language>eng</language><publisher>Dordrecht: Springer</publisher><subject>Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alleles ; Biomedical and Life Sciences ; Biomedicine ; Brain cancer ; Brain Neoplasms - blood ; Brain Neoplasms - epidemiology ; Brain Neoplasms - genetics ; Brain research ; Cancer ; Cancer Research ; Case-Control Studies ; Dietary iron ; DNA damage ; DNA, Neoplasm - genetics ; Epidemiology ; Female ; Ferritins - blood ; Follow-Up Studies ; Genetic testing ; Genotype ; Genotypes ; Glioma ; Glioma - blood ; Glioma - epidemiology ; Glioma - genetics ; Hematology ; Humans ; Iron ; Iron - metabolism ; Iron, Dietary ; Male ; Medical genetics ; Metabolism ; Middle Aged ; Nails - chemistry ; Neoplasm Grading ; Neoplasm Proteins - genetics ; Neurosurgery ; Oncology ; Original Paper ; P values ; Polymerase Chain Reaction ; Prognosis ; Public Health ; Risk Factors ; Survival Rate ; Toenails ; Tumors ; Young Adult</subject><ispartof>Cancer causes &amp; control, 2013-12, Vol.24 (12), p.2051-2058</ispartof><rights>Springer Science+Business Media 2013</rights><rights>Springer Science+Business Media Dordrecht 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c492t-3b67fb3b9ea84c7ecef3cc76a409054c2072528569a1e39a35df947914a844373</citedby><cites>FETCH-LOGICAL-c492t-3b67fb3b9ea84c7ecef3cc76a409054c2072528569a1e39a35df947914a844373</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/24717889$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/24717889$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,58216,58449</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23996192$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Anic, Gabriella M.</creatorcontrib><creatorcontrib>Madden, Melissa H.</creatorcontrib><creatorcontrib>Thompson, Reid C.</creatorcontrib><creatorcontrib>Nabors, L. Burton</creatorcontrib><creatorcontrib>Olson, Jeffrey J.</creatorcontrib><creatorcontrib>LaRocca, Renato V.</creatorcontrib><creatorcontrib>Browning, James E.</creatorcontrib><creatorcontrib>Brockman, John D.</creatorcontrib><creatorcontrib>Forsyth, Peter A.</creatorcontrib><creatorcontrib>Egan, Kathleen M.</creatorcontrib><title>Toenail iron, genetic determinants of iron status, and the risk of glioma</title><title>Cancer causes &amp; control</title><addtitle>Cancer Causes Control</addtitle><addtitle>Cancer Causes Control</addtitle><description>Purpose: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case–control study. Methods: Samples were collected a median of 24 days following glioma diagnosis in the cases (10th–90th percentile, range: 10–44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. Results: No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ∼3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 μ/g) vs. low (&lt;6 μ/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants. Conclusion: The results do not support a role for body iron stores as a determinant of glioma risk.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Alleles</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain cancer</subject><subject>Brain Neoplasms - blood</subject><subject>Brain Neoplasms - epidemiology</subject><subject>Brain Neoplasms - genetics</subject><subject>Brain research</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Case-Control Studies</subject><subject>Dietary iron</subject><subject>DNA damage</subject><subject>DNA, Neoplasm - genetics</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Ferritins - blood</subject><subject>Follow-Up Studies</subject><subject>Genetic testing</subject><subject>Genotype</subject><subject>Genotypes</subject><subject>Glioma</subject><subject>Glioma - blood</subject><subject>Glioma - epidemiology</subject><subject>Glioma - genetics</subject><subject>Hematology</subject><subject>Humans</subject><subject>Iron</subject><subject>Iron - metabolism</subject><subject>Iron, Dietary</subject><subject>Male</subject><subject>Medical genetics</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Nails - chemistry</subject><subject>Neoplasm Grading</subject><subject>Neoplasm Proteins - genetics</subject><subject>Neurosurgery</subject><subject>Oncology</subject><subject>Original Paper</subject><subject>P values</subject><subject>Polymerase Chain Reaction</subject><subject>Prognosis</subject><subject>Public Health</subject><subject>Risk Factors</subject><subject>Survival Rate</subject><subject>Toenails</subject><subject>Tumors</subject><subject>Young Adult</subject><issn>0957-5243</issn><issn>1573-7225</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kU9v1DAQxS1ERZfCB-AAisSFQwPjf3F8qYSqApUqcSlny-udbL0kdrEdJL59vU0pbQ-c5vB-782MHiFvKHykAOpTpiAla4HyFlhPW_aMrKhUvFWMyedkBVqqVjLBD8nLnHcAIDsGL8gh41p3VLMVOb-MGKwfG59iOG62GLB412ywYJp8sKHkJg63apOLLXM-bmzYNOUKm-Tzz724HX2c7CtyMNgx4-u7eUR-fDm7PP3WXnz_en76-aJ1QrPS8nWnhjVfa7S9cAodDtw51VkBGqRwDBSTrJedthS5tlxuBi2UpqLygit-RE6W3Ot5PeHGYSjJjuY6-cmmPyZabx4rwV-ZbfxteM94p2UN-HAXkOKvGXMxk88Ox9EGjHM2VNRDe-BcV_T9E3QX5xTqe3uq7wEYQKXoQrkUc0443B9DweyLMktRphZl9kUZVj3vHn5x7_jbTAXYAuQqhS2mB6v_k_p2Me1yielfqFBU9b3mN0vKpqo</recordid><startdate>20131201</startdate><enddate>20131201</enddate><creator>Anic, Gabriella M.</creator><creator>Madden, Melissa H.</creator><creator>Thompson, Reid C.</creator><creator>Nabors, L. 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Burton ; Olson, Jeffrey J. ; LaRocca, Renato V. ; Browning, James E. ; Brockman, John D. ; Forsyth, Peter A. ; Egan, Kathleen M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c492t-3b67fb3b9ea84c7ecef3cc76a409054c2072528569a1e39a35df947914a844373</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Alleles</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Brain cancer</topic><topic>Brain Neoplasms - blood</topic><topic>Brain Neoplasms - epidemiology</topic><topic>Brain Neoplasms - genetics</topic><topic>Brain research</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Case-Control Studies</topic><topic>Dietary iron</topic><topic>DNA damage</topic><topic>DNA, Neoplasm - genetics</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Ferritins - blood</topic><topic>Follow-Up Studies</topic><topic>Genetic testing</topic><topic>Genotype</topic><topic>Genotypes</topic><topic>Glioma</topic><topic>Glioma - blood</topic><topic>Glioma - epidemiology</topic><topic>Glioma - genetics</topic><topic>Hematology</topic><topic>Humans</topic><topic>Iron</topic><topic>Iron - metabolism</topic><topic>Iron, Dietary</topic><topic>Male</topic><topic>Medical genetics</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Nails - chemistry</topic><topic>Neoplasm Grading</topic><topic>Neoplasm Proteins - genetics</topic><topic>Neurosurgery</topic><topic>Oncology</topic><topic>Original Paper</topic><topic>P values</topic><topic>Polymerase Chain Reaction</topic><topic>Prognosis</topic><topic>Public Health</topic><topic>Risk Factors</topic><topic>Survival Rate</topic><topic>Toenails</topic><topic>Tumors</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Anic, Gabriella M.</creatorcontrib><creatorcontrib>Madden, Melissa H.</creatorcontrib><creatorcontrib>Thompson, Reid C.</creatorcontrib><creatorcontrib>Nabors, L. 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Burton</au><au>Olson, Jeffrey J.</au><au>LaRocca, Renato V.</au><au>Browning, James E.</au><au>Brockman, John D.</au><au>Forsyth, Peter A.</au><au>Egan, Kathleen M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Toenail iron, genetic determinants of iron status, and the risk of glioma</atitle><jtitle>Cancer causes &amp; control</jtitle><stitle>Cancer Causes Control</stitle><addtitle>Cancer Causes Control</addtitle><date>2013-12-01</date><risdate>2013</risdate><volume>24</volume><issue>12</issue><spage>2051</spage><epage>2058</epage><pages>2051-2058</pages><issn>0957-5243</issn><eissn>1573-7225</eissn><coden>CCCNEN</coden><abstract>Purpose: Iron is essential for oxygen transport and oxidative metabolism; however, elevated iron stores can trigger overproduction of reactive oxygen species and induce DNA damage. Little is known about the association between body iron stores and glioma risk. This study examined the associations of iron levels measured in toenails and genetic variants linked to body iron stores with risk of glioma in a clinic-based case–control study. Methods: Samples were collected a median of 24 days following glioma diagnosis in the cases (10th–90th percentile, range: 10–44 days). Nail iron levels were measured in 300 cases and 300 controls using neutron activation analysis. A total of 24 genetic variants associated with iron status were genotyped in 622 cases and 628 controls. Logistic regression was used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for glioma risk according to toenail iron and the examined genotypes. Results: No association was observed between toenail iron and glioma risk when restricting to cases with nails collected within ∼3 weeks of diagnosis (OR = 0.93; 95 % CI 0.46, 1.87 comparing those with high (≥14 μ/g) vs. low (&lt;6 μ/g) iron levels). In contrast, an inverse association with increasing iron was observed after restricting to cases with a delay of 3 weeks or greater (OR = 0.42; 95 % CI 0.19, 0.95), reflecting potentially insidious effects of advancing disease on iron levels among the cases. No associations were observed for any of the examined genetic variants. Conclusion: The results do not support a role for body iron stores as a determinant of glioma risk.</abstract><cop>Dordrecht</cop><pub>Springer</pub><pmid>23996192</pmid><doi>10.1007/s10552-013-0281-2</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Aged
Aged, 80 and over
Alleles
Biomedical and Life Sciences
Biomedicine
Brain cancer
Brain Neoplasms - blood
Brain Neoplasms - epidemiology
Brain Neoplasms - genetics
Brain research
Cancer
Cancer Research
Case-Control Studies
Dietary iron
DNA damage
DNA, Neoplasm - genetics
Epidemiology
Female
Ferritins - blood
Follow-Up Studies
Genetic testing
Genotype
Genotypes
Glioma
Glioma - blood
Glioma - epidemiology
Glioma - genetics
Hematology
Humans
Iron
Iron - metabolism
Iron, Dietary
Male
Medical genetics
Metabolism
Middle Aged
Nails - chemistry
Neoplasm Grading
Neoplasm Proteins - genetics
Neurosurgery
Oncology
Original Paper
P values
Polymerase Chain Reaction
Prognosis
Public Health
Risk Factors
Survival Rate
Toenails
Tumors
Young Adult
title Toenail iron, genetic determinants of iron status, and the risk of glioma
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