Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood
Background: DNA methylation markers have been associated with lung cancer risk and may identify aetiologically relevant genomic regions, or alternatively, be markers of disease risk factors or biological processes associated with disease development. Methods: In a nested case-control study, we measu...
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| Veröffentlicht in: | Epigenetics 2022-04, Vol.17 (4), p.460-472 |
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| creator | Zhao, Naisi Ruan, Mengyuan Koestler, Devin C. Lu, Jiayun Marsit, Carmen J. Kelsey, Karl T. Platz, Elizabeth A. Michaud, Dominique S. |
| description | Background: DNA methylation markers have been associated with lung cancer risk and may identify aetiologically relevant genomic regions, or alternatively, be markers of disease risk factors or biological processes associated with disease development.
Methods: In a nested case-control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 participants (208 cases; 222 controls) in the 1989 CLUE II cohort. We compared DNA methylation levels with case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years-based smoking methylation score. Stratification analyses were conducted over time from blood draw to diagnosis, histology, and smoking status.
Results: We identified 16 single CpG sites and 40 DMRs significantly associated with lung cancer risk (q |
| doi_str_mv | 10.1080/15592294.2021.1923615 |
| format | Article |
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Methods: In a nested case-control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 participants (208 cases; 222 controls) in the 1989 CLUE II cohort. We compared DNA methylation levels with case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years-based smoking methylation score. Stratification analyses were conducted over time from blood draw to diagnosis, histology, and smoking status.
Results: We identified 16 single CpG sites and 40 DMRs significantly associated with lung cancer risk (q < 0.05). The identified genomic regions were associated with genes including H19, HOXA3/HOXA4, RUNX3, BRICD5, PLXNB2, and RP13. For the single CpG sites, the strongest association was noted for cg09736286 in the DIABLO gene (OR [for 1 SD] = 2.99, 95% CI: 1.95-4.59, P-value = 4.81 × 10-7). We found that CpG sites in the HOXA3/HOXA4 region were hypermethylated in cases compared to controls.
Conclusion: The single CpG sites and DMRs that we identified represented significant measurable differences in lung cancer risk, providing potential biomarkers for lung cancer risk stratification. Future studies will need to examine whether these regions are causally related to lung cancer.</description><identifier>ISSN: 1559-2294</identifier><identifier>EISSN: 1559-2308</identifier><identifier>DOI: 10.1080/15592294.2021.1923615</identifier><identifier>PMID: 34008478</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>blood ; Case-Control Studies ; CpG Islands ; DNA Methylation ; Epigenesis, Genetic ; Epigenome ; epigenome-wide association study (EWAS) ; Genome-Wide Association Study ; Humans ; Illumina MethylationEPIC array ; Lung cancer ; Lung Neoplasms - diagnosis ; Lung Neoplasms - genetics ; Research Paper</subject><ispartof>Epigenetics, 2022-04, Vol.17 (4), p.460-472</ispartof><rights>2021 Informa UK Limited, trading as Taylor & Francis Group 2021</rights><rights>2021 Informa UK Limited, trading as Taylor & Francis Group 2021 Informa UK Limited, trading as Taylor & Francis Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-91e7fc9be7c7f0badcb54bcac523f469d65a9ba489fe094587a3c03179c7cc153</citedby><cites>FETCH-LOGICAL-c534t-91e7fc9be7c7f0badcb54bcac523f469d65a9ba489fe094587a3c03179c7cc153</cites><orcidid>0000-0002-8107-3011 ; 0000-0001-7555-8963 ; 0000-0002-0517-0709 ; 0000-0003-4566-150X ; 0000-0002-0598-0146</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993104/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8993104/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34008478$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhao, Naisi</creatorcontrib><creatorcontrib>Ruan, Mengyuan</creatorcontrib><creatorcontrib>Koestler, Devin C.</creatorcontrib><creatorcontrib>Lu, Jiayun</creatorcontrib><creatorcontrib>Marsit, Carmen J.</creatorcontrib><creatorcontrib>Kelsey, Karl T.</creatorcontrib><creatorcontrib>Platz, Elizabeth A.</creatorcontrib><creatorcontrib>Michaud, Dominique S.</creatorcontrib><title>Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood</title><title>Epigenetics</title><addtitle>Epigenetics</addtitle><description>Background: DNA methylation markers have been associated with lung cancer risk and may identify aetiologically relevant genomic regions, or alternatively, be markers of disease risk factors or biological processes associated with disease development.
Methods: In a nested case-control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 participants (208 cases; 222 controls) in the 1989 CLUE II cohort. We compared DNA methylation levels with case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years-based smoking methylation score. Stratification analyses were conducted over time from blood draw to diagnosis, histology, and smoking status.
Results: We identified 16 single CpG sites and 40 DMRs significantly associated with lung cancer risk (q < 0.05). The identified genomic regions were associated with genes including H19, HOXA3/HOXA4, RUNX3, BRICD5, PLXNB2, and RP13. For the single CpG sites, the strongest association was noted for cg09736286 in the DIABLO gene (OR [for 1 SD] = 2.99, 95% CI: 1.95-4.59, P-value = 4.81 × 10-7). We found that CpG sites in the HOXA3/HOXA4 region were hypermethylated in cases compared to controls.
Conclusion: The single CpG sites and DMRs that we identified represented significant measurable differences in lung cancer risk, providing potential biomarkers for lung cancer risk stratification. Future studies will need to examine whether these regions are causally related to lung cancer.</description><subject>blood</subject><subject>Case-Control Studies</subject><subject>CpG Islands</subject><subject>DNA Methylation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenome</subject><subject>epigenome-wide association study (EWAS)</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Illumina MethylationEPIC array</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - genetics</subject><subject>Research Paper</subject><issn>1559-2294</issn><issn>1559-2308</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>DOA</sourceid><recordid>eNp9kc9u1DAQxi0EomXhEUB-gSz-m8QXBKoKVKrEBc6WY4-zrpw4srOt9u3rZbsVvXDyzHi-b-z5IfSRki0lPflMpVSMKbFlhNEtVYy3VL5Cl8d6wzjpX5_j2nSB3pVyR4jgrVJv0QUXhPSi6y_R_fUSRpjTBM1DcICLNTOuwbwGH6BgF7yHfExNjAc8wbo7RLOCwxnGkOaCfco47ucRV6WFjPcl1GTJ0LhgxjmVNVi8QA7LDrKJeIgpuffojTexwIenc4P-fL_-ffWzuf314-bq221jJRdroyh03qoBOtt5MhhnBykGa6xk3ItWuVYaNRjRKw9ECdl3hlvCaadsZy2VfINuTr4umTu95DCZfNDJBP23kPKoTa4PjKBZaxhz3DkwVjDq-r5zbmCDlY5I1tnq9eXkteyHCZytS6n_eWH68mYOOz2me90rxWnd_QbJk4HNqZQM_llLiT5C1Weo-ghVP0Gtuk__Dn5WnSnWhq-nhjBXGpN5SDk6vZpDTNnniiUUzf8_4xHWgLZP</recordid><startdate>20220403</startdate><enddate>20220403</enddate><creator>Zhao, Naisi</creator><creator>Ruan, Mengyuan</creator><creator>Koestler, Devin C.</creator><creator>Lu, Jiayun</creator><creator>Marsit, Carmen J.</creator><creator>Kelsey, Karl T.</creator><creator>Platz, Elizabeth A.</creator><creator>Michaud, Dominique S.</creator><general>Taylor & Francis</general><general>Taylor & Francis Group</general><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>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-8107-3011</orcidid><orcidid>https://orcid.org/0000-0001-7555-8963</orcidid><orcidid>https://orcid.org/0000-0002-0517-0709</orcidid><orcidid>https://orcid.org/0000-0003-4566-150X</orcidid><orcidid>https://orcid.org/0000-0002-0598-0146</orcidid></search><sort><creationdate>20220403</creationdate><title>Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood</title><author>Zhao, Naisi ; Ruan, Mengyuan ; Koestler, Devin C. ; Lu, Jiayun ; Marsit, Carmen J. ; Kelsey, Karl T. ; Platz, Elizabeth A. ; Michaud, Dominique S.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-91e7fc9be7c7f0badcb54bcac523f469d65a9ba489fe094587a3c03179c7cc153</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>blood</topic><topic>Case-Control Studies</topic><topic>CpG Islands</topic><topic>DNA Methylation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenome</topic><topic>epigenome-wide association study (EWAS)</topic><topic>Genome-Wide Association Study</topic><topic>Humans</topic><topic>Illumina MethylationEPIC array</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - genetics</topic><topic>Research Paper</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhao, Naisi</creatorcontrib><creatorcontrib>Ruan, Mengyuan</creatorcontrib><creatorcontrib>Koestler, Devin C.</creatorcontrib><creatorcontrib>Lu, Jiayun</creatorcontrib><creatorcontrib>Marsit, Carmen J.</creatorcontrib><creatorcontrib>Kelsey, Karl T.</creatorcontrib><creatorcontrib>Platz, Elizabeth A.</creatorcontrib><creatorcontrib>Michaud, Dominique S.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Epigenetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhao, Naisi</au><au>Ruan, Mengyuan</au><au>Koestler, Devin C.</au><au>Lu, Jiayun</au><au>Marsit, Carmen J.</au><au>Kelsey, Karl T.</au><au>Platz, Elizabeth A.</au><au>Michaud, Dominique S.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood</atitle><jtitle>Epigenetics</jtitle><addtitle>Epigenetics</addtitle><date>2022-04-03</date><risdate>2022</risdate><volume>17</volume><issue>4</issue><spage>460</spage><epage>472</epage><pages>460-472</pages><issn>1559-2294</issn><eissn>1559-2308</eissn><abstract>Background: DNA methylation markers have been associated with lung cancer risk and may identify aetiologically relevant genomic regions, or alternatively, be markers of disease risk factors or biological processes associated with disease development.
Methods: In a nested case-control study, we measured blood leukocyte DNA methylation levels in pre-diagnostic samples collected from 430 participants (208 cases; 222 controls) in the 1989 CLUE II cohort. We compared DNA methylation levels with case/control status to identify novel genomic regions, both single CpG sites and differentially methylated regions (DMRs), while controlling for known DNA methylation changes associated with smoking using a previously described pack-years-based smoking methylation score. Stratification analyses were conducted over time from blood draw to diagnosis, histology, and smoking status.
Results: We identified 16 single CpG sites and 40 DMRs significantly associated with lung cancer risk (q < 0.05). The identified genomic regions were associated with genes including H19, HOXA3/HOXA4, RUNX3, BRICD5, PLXNB2, and RP13. For the single CpG sites, the strongest association was noted for cg09736286 in the DIABLO gene (OR [for 1 SD] = 2.99, 95% CI: 1.95-4.59, P-value = 4.81 × 10-7). We found that CpG sites in the HOXA3/HOXA4 region were hypermethylated in cases compared to controls.
Conclusion: The single CpG sites and DMRs that we identified represented significant measurable differences in lung cancer risk, providing potential biomarkers for lung cancer risk stratification. Future studies will need to examine whether these regions are causally related to lung cancer.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>34008478</pmid><doi>10.1080/15592294.2021.1923615</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-8107-3011</orcidid><orcidid>https://orcid.org/0000-0001-7555-8963</orcidid><orcidid>https://orcid.org/0000-0002-0517-0709</orcidid><orcidid>https://orcid.org/0000-0003-4566-150X</orcidid><orcidid>https://orcid.org/0000-0002-0598-0146</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | blood Case-Control Studies CpG Islands DNA Methylation Epigenesis, Genetic Epigenome epigenome-wide association study (EWAS) Genome-Wide Association Study Humans Illumina MethylationEPIC array Lung cancer Lung Neoplasms - diagnosis Lung Neoplasms - genetics Research Paper |
| title | Epigenome-wide scan identifies differentially methylated regions for lung cancer using pre-diagnostic peripheral blood |
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