Association between global DNA hypomethylation in leukocytes and risk of breast cancer
Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I–IIIa) an...
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| Veröffentlicht in: | Carcinogenesis (New York) 2009-11, Vol.30 (11), p.1889-1897 |
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| container_title | Carcinogenesis (New York) |
| container_volume | 30 |
| creator | Choi, Ji-Yeob James, Smitha R. Link, Petra A. McCann, Susan E. Hong, Chi-Chen Davis, Warren Nesline, Mary K. Ambrosone, Christine B. Karpf, Adam R. |
| description | Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I–IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. Results: In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case–control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value |
| doi_str_mv | 10.1093/carcin/bgp143 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2783000</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/carcin/bgp143</oup_id><sourcerecordid>21189884</sourcerecordid><originalsourceid>FETCH-LOGICAL-c554t-e6852f173989348a4680dfc609647212852e47dee7ea5ff5a731698cd8c8add43</originalsourceid><addsrcrecordid>eNqFkc1v1DAQxS0EarelR67IJ9RLqB07iX2ptNoCRZSPQ1kQF8txJrvuZu3Udgr735Mqq9KeOI0076f3RvMQekXJW0okOzM6GOvO6lVPOXuGZpSXJMupIM_RjIyrjDHGD9FRjDeE0JIV8gAdUlkITpmcoeU8Rm-sTtY7XEP6DeDwqvO17vDFlzle73q_hbTedRNiHe5g2HizSxCxdg0ONm6wb3EdQMeEjXYGwkv0otVdhJP9PEbf37-7XlxmV18_fFzMrzJTFDxlUIoib2nFpJCMC81LQZrWlESWvMppPqrAqwagAl20baErRkspTCOM0E3D2TE6n3z7od5CY8CloDvVB7vVYae8tuqp4uxarfydyivBCCGjwZu9QfC3A8SktjYa6DrtwA9R5ZQKKcR9UjaBJvgYA7QPIZSo-ybU1ISamhj5148v-0fvXz8CpxPgh_6_XvtsGxP8eYB12KiyYlWhLn_-Up8X159-LOk3tWR_AW6GpVY</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>21189884</pqid></control><display><type>article</type><title>Association between global DNA hypomethylation in leukocytes and risk of breast cancer</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Choi, Ji-Yeob ; James, Smitha R. ; Link, Petra A. ; McCann, Susan E. ; Hong, Chi-Chen ; Davis, Warren ; Nesline, Mary K. ; Ambrosone, Christine B. ; Karpf, Adam R.</creator><creatorcontrib>Choi, Ji-Yeob ; James, Smitha R. ; Link, Petra A. ; McCann, Susan E. ; Hong, Chi-Chen ; Davis, Warren ; Nesline, Mary K. ; Ambrosone, Christine B. ; Karpf, Adam R.</creatorcontrib><description>Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I–IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. Results: In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case–control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84–2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65–4.94) had higher risk of breast cancer (P for trend ≤0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. Conclusion: These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer.</description><identifier>ISSN: 0143-3334</identifier><identifier>EISSN: 1460-2180</identifier><identifier>DOI: 10.1093/carcin/bgp143</identifier><identifier>PMID: 19584139</identifier><language>eng</language><publisher>England: Oxford University Press</publisher><subject>5-Methylcytosine - analogs & derivatives ; Adult ; Aged ; Alcohol Drinking ; Breast Neoplasms - blood ; Breast Neoplasms - genetics ; Breast Neoplasms - pathology ; Confidence Intervals ; Dietary Supplements ; DNA Methylation ; DNA, Neoplasm - genetics ; DNA, Neoplasm - metabolism ; Female ; Humans ; Leukocytes - metabolism ; Middle Aged ; Molecular Epidemiology ; Neoplasm Staging ; Odds Ratio ; Repetitive Sequences, Nucleic Acid ; Risk ; Risk Factors ; Smoking</subject><ispartof>Carcinogenesis (New York), 2009-11, Vol.30 (11), p.1889-1897</ispartof><rights>The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org 2009</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c554t-e6852f173989348a4680dfc609647212852e47dee7ea5ff5a731698cd8c8add43</citedby><cites>FETCH-LOGICAL-c554t-e6852f173989348a4680dfc609647212852e47dee7ea5ff5a731698cd8c8add43</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19584139$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Choi, Ji-Yeob</creatorcontrib><creatorcontrib>James, Smitha R.</creatorcontrib><creatorcontrib>Link, Petra A.</creatorcontrib><creatorcontrib>McCann, Susan E.</creatorcontrib><creatorcontrib>Hong, Chi-Chen</creatorcontrib><creatorcontrib>Davis, Warren</creatorcontrib><creatorcontrib>Nesline, Mary K.</creatorcontrib><creatorcontrib>Ambrosone, Christine B.</creatorcontrib><creatorcontrib>Karpf, Adam R.</creatorcontrib><title>Association between global DNA hypomethylation in leukocytes and risk of breast cancer</title><title>Carcinogenesis (New York)</title><addtitle>Carcinogenesis</addtitle><description>Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I–IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. Results: In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case–control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84–2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65–4.94) had higher risk of breast cancer (P for trend ≤0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. Conclusion: These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer.</description><subject>5-Methylcytosine - analogs & derivatives</subject><subject>Adult</subject><subject>Aged</subject><subject>Alcohol Drinking</subject><subject>Breast Neoplasms - blood</subject><subject>Breast Neoplasms - genetics</subject><subject>Breast Neoplasms - pathology</subject><subject>Confidence Intervals</subject><subject>Dietary Supplements</subject><subject>DNA Methylation</subject><subject>DNA, Neoplasm - genetics</subject><subject>DNA, Neoplasm - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Leukocytes - metabolism</subject><subject>Middle Aged</subject><subject>Molecular Epidemiology</subject><subject>Neoplasm Staging</subject><subject>Odds Ratio</subject><subject>Repetitive Sequences, Nucleic Acid</subject><subject>Risk</subject><subject>Risk Factors</subject><subject>Smoking</subject><issn>0143-3334</issn><issn>1460-2180</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc1v1DAQxS0EarelR67IJ9RLqB07iX2ptNoCRZSPQ1kQF8txJrvuZu3Udgr735Mqq9KeOI0076f3RvMQekXJW0okOzM6GOvO6lVPOXuGZpSXJMupIM_RjIyrjDHGD9FRjDeE0JIV8gAdUlkITpmcoeU8Rm-sTtY7XEP6DeDwqvO17vDFlzle73q_hbTedRNiHe5g2HizSxCxdg0ONm6wb3EdQMeEjXYGwkv0otVdhJP9PEbf37-7XlxmV18_fFzMrzJTFDxlUIoib2nFpJCMC81LQZrWlESWvMppPqrAqwagAl20baErRkspTCOM0E3D2TE6n3z7od5CY8CloDvVB7vVYae8tuqp4uxarfydyivBCCGjwZu9QfC3A8SktjYa6DrtwA9R5ZQKKcR9UjaBJvgYA7QPIZSo-ybU1ISamhj5148v-0fvXz8CpxPgh_6_XvtsGxP8eYB12KiyYlWhLn_-Up8X159-LOk3tWR_AW6GpVY</recordid><startdate>20091101</startdate><enddate>20091101</enddate><creator>Choi, Ji-Yeob</creator><creator>James, Smitha R.</creator><creator>Link, Petra A.</creator><creator>McCann, Susan E.</creator><creator>Hong, Chi-Chen</creator><creator>Davis, Warren</creator><creator>Nesline, Mary K.</creator><creator>Ambrosone, Christine B.</creator><creator>Karpf, Adam R.</creator><general>Oxford University Press</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TM</scope><scope>H94</scope><scope>5PM</scope></search><sort><creationdate>20091101</creationdate><title>Association between global DNA hypomethylation in leukocytes and risk of breast cancer</title><author>Choi, Ji-Yeob ; James, Smitha R. ; Link, Petra A. ; McCann, Susan E. ; Hong, Chi-Chen ; Davis, Warren ; Nesline, Mary K. ; Ambrosone, Christine B. ; Karpf, Adam R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c554t-e6852f173989348a4680dfc609647212852e47dee7ea5ff5a731698cd8c8add43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>5-Methylcytosine - analogs & derivatives</topic><topic>Adult</topic><topic>Aged</topic><topic>Alcohol Drinking</topic><topic>Breast Neoplasms - blood</topic><topic>Breast Neoplasms - genetics</topic><topic>Breast Neoplasms - pathology</topic><topic>Confidence Intervals</topic><topic>Dietary Supplements</topic><topic>DNA Methylation</topic><topic>DNA, Neoplasm - genetics</topic><topic>DNA, Neoplasm - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Leukocytes - metabolism</topic><topic>Middle Aged</topic><topic>Molecular Epidemiology</topic><topic>Neoplasm Staging</topic><topic>Odds Ratio</topic><topic>Repetitive Sequences, Nucleic Acid</topic><topic>Risk</topic><topic>Risk Factors</topic><topic>Smoking</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Choi, Ji-Yeob</creatorcontrib><creatorcontrib>James, Smitha R.</creatorcontrib><creatorcontrib>Link, Petra A.</creatorcontrib><creatorcontrib>McCann, Susan E.</creatorcontrib><creatorcontrib>Hong, Chi-Chen</creatorcontrib><creatorcontrib>Davis, Warren</creatorcontrib><creatorcontrib>Nesline, Mary K.</creatorcontrib><creatorcontrib>Ambrosone, Christine B.</creatorcontrib><creatorcontrib>Karpf, Adam R.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Carcinogenesis (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Choi, Ji-Yeob</au><au>James, Smitha R.</au><au>Link, Petra A.</au><au>McCann, Susan E.</au><au>Hong, Chi-Chen</au><au>Davis, Warren</au><au>Nesline, Mary K.</au><au>Ambrosone, Christine B.</au><au>Karpf, Adam R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Association between global DNA hypomethylation in leukocytes and risk of breast cancer</atitle><jtitle>Carcinogenesis (New York)</jtitle><addtitle>Carcinogenesis</addtitle><date>2009-11-01</date><risdate>2009</risdate><volume>30</volume><issue>11</issue><spage>1889</spage><epage>1897</epage><pages>1889-1897</pages><issn>0143-3334</issn><eissn>1460-2180</eissn><abstract>Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I–IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. Results: In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case–control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84–2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65–4.94) had higher risk of breast cancer (P for trend ≤0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. Conclusion: These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer.</abstract><cop>England</cop><pub>Oxford University Press</pub><pmid>19584139</pmid><doi>10.1093/carcin/bgp143</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | 5-Methylcytosine - analogs & derivatives Adult Aged Alcohol Drinking Breast Neoplasms - blood Breast Neoplasms - genetics Breast Neoplasms - pathology Confidence Intervals Dietary Supplements DNA Methylation DNA, Neoplasm - genetics DNA, Neoplasm - metabolism Female Humans Leukocytes - metabolism Middle Aged Molecular Epidemiology Neoplasm Staging Odds Ratio Repetitive Sequences, Nucleic Acid Risk Risk Factors Smoking |
| title | Association between global DNA hypomethylation in leukocytes and risk of breast cancer |
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