Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses
Background Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment in...
Gespeichert in:
| Veröffentlicht in: | British journal of cancer 2023-08, Vol.129 (3), p.511-520 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 520 |
|---|---|
| container_issue | 3 |
| container_start_page | 511 |
| container_title | British journal of cancer |
| container_volume | 129 |
| creator | Dimou, Niki Kim, Andre E. Flanagan, Orlagh Murphy, Neil Diez-Obrero, Virginia Shcherbina, Anna Aglago, Elom K. Bouras, Emmanouil Campbell, Peter T. Casey, Graham Gallinger, Steven Gruber, Stephen B. Jenkins, Mark A. Lin, Yi Moreno, Victor Ruiz-Narvaez, Edward Stern, Mariana C. Tian, Yu Tsilidis, Kostas K. Arndt, Volker Barry, Elizabeth L. Baurley, James W. Berndt, Sonja I. Bézieau, Stéphane Bien, Stephanie A. Bishop, D. Timothy Brenner, Hermann Budiarto, Arif Carreras-Torres, Robert Cenggoro, Tjeng Wawan Chan, Andrew T. Chang-Claude, Jenny Chanock, Stephen J. Chen, Xuechen Conti, David V. Dampier, Christopher H. Devall, Matthew Drew, David A. Figueiredo, Jane C. Giles, Graham G. Gsur, Andrea Harrison, Tabitha A. Hidaka, Akihisa Hoffmeister, Michael Huyghe, Jeroen R. Jordahl, Kristina Kawaguchi, Eric Keku, Temitope O. Larsson, Susanna C. Le Marchand, Loic Lewinger, Juan Pablo Li, Li Mahesworo, Bharuno Morrison, John Newcomb, Polly A. Newton, Christina C. Obon-Santacana, Mireia Ose, Jennifer Pai, Rish K. Palmer, Julie R. Papadimitriou, Nikos Pardamean, Bens Peoples, Anita R. Pharoah, Paul D. P. Platz, Elizabeth A. Potter, John D. Rennert, Gad Scacheri, Peter C. Schoen, Robert E. Su, Yu-Ru Tangen, Catherine M. Thibodeau, Stephen N. Thomas, Duncan C. Ulrich, Cornelia M. Um, Caroline Y. van Duijnhoven, Franzel J. B. Visvanathan, Kala Vodicka, Pavel Vodickova, Ludmila White, Emily Wolk, Alicja Woods, Michael O. Qu, Conghui Kundaje, Anshul Hsu, Li Gauderman, W. James Gunter, Marc J. Peters, Ulrike |
| description | Background
Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis.
Methods
We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test).
Results
Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177,
SLC30A8 –
OR
AA
: 1.62, 95% CI: 1.34–1.96; OR
AG
: 1.41, 95% CI: 1.30–1.54; OR
GG
: 1.22, 95% CI: 1.13–1.31;
p
-value
3-d.f.
: 5.46 × 10
−11
) and 13q14.13 (rs9526201,
LRCH1 –
OR
GG
: 2.11, 95% CI: 1.56–2.83; OR
GA
: 1.52, 95% CI: 1.38–1.68; OR
AA
: 1.13, 95% CI: 1.06–1.21;
p
-value
2-d.f.
: 7.84 × 10
−09
).
Discussion
These results suggest that variation in genes related to insulin signaling (
SLC30A8
) and immune function (
LRCH1
) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship. |
| doi_str_mv | 10.1038/s41416-023-02312-z |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_swepu</sourceid><recordid>TN_cdi_swepub_primary_oai_swepub_ki_se_445548</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2830213384</sourcerecordid><originalsourceid>FETCH-LOGICAL-c513t-88441ae7f7aff35bfe74cf5239a5ff546281800a8ae2169b8c6589685e8dd77f3</originalsourceid><addsrcrecordid>eNp9kbtuFDEUhi0EIkvgBSiQJRqaAV_HngqhiJsUCQqoLY_neNdh1l7smURJxTvkDfMkeNglEAoKy5fz_b-P_SP0lJKXlHD9qggqaNsQxpdBWXN1D62o5Kyhmqn7aEUIUQ3pGDlCj0o5q9uOaPUQHXHFW8m0XKH155z6ENd42gAegu1hgoJtHLBLY8rgJjtiZ6ODjDOMdgoplk3Y4bksqjVEwDc_rjHE85BT3EKccIgTZOsWtDrZ8bJAeYweeDsWeHKYj9HXd2-_nHxoTj-9_3jy5rRxkvKp0VoIakF5Zb3nsveghPOS8c5K76VomaaaEKstMNp2vXat1F2rJehhUMrzY9TsfcsF7Obe7HLY2nxpkg3mcPStrsAIIaXQlX-952tlC4Or_Wc73pHdrcSwMet0bigRhEtGq8OLg0NO32cok9mG4mAcbYQ0F8M0JxXjWlT0-T_oWZpz_aGFErJTmmhZKbanXE6lZPC33VBiluDNPnhTQze_gjdXVfTs73fcSn4nXQF--JhaimvIf-7-j-1PAo69Hw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2845978085</pqid></control><display><type>article</type><title>Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses</title><source>PubMed (Medline)</source><source>MEDLINE</source><source>SWEPUB Freely available online</source><source>EZB Electronic Journals Library</source><source>SpringerLink Journals - AutoHoldings</source><creator>Dimou, Niki ; Kim, Andre E. ; Flanagan, Orlagh ; Murphy, Neil ; Diez-Obrero, Virginia ; Shcherbina, Anna ; Aglago, Elom K. ; Bouras, Emmanouil ; Campbell, Peter T. ; Casey, Graham ; Gallinger, Steven ; Gruber, Stephen B. ; Jenkins, Mark A. ; Lin, Yi ; Moreno, Victor ; Ruiz-Narvaez, Edward ; Stern, Mariana C. ; Tian, Yu ; Tsilidis, Kostas K. ; Arndt, Volker ; Barry, Elizabeth L. ; Baurley, James W. ; Berndt, Sonja I. ; Bézieau, Stéphane ; Bien, Stephanie A. ; Bishop, D. Timothy ; Brenner, Hermann ; Budiarto, Arif ; Carreras-Torres, Robert ; Cenggoro, Tjeng Wawan ; Chan, Andrew T. ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Chen, Xuechen ; Conti, David V. ; Dampier, Christopher H. ; Devall, Matthew ; Drew, David A. ; Figueiredo, Jane C. ; Giles, Graham G. ; Gsur, Andrea ; Harrison, Tabitha A. ; Hidaka, Akihisa ; Hoffmeister, Michael ; Huyghe, Jeroen R. ; Jordahl, Kristina ; Kawaguchi, Eric ; Keku, Temitope O. ; Larsson, Susanna C. ; Le Marchand, Loic ; Lewinger, Juan Pablo ; Li, Li ; Mahesworo, Bharuno ; Morrison, John ; Newcomb, Polly A. ; Newton, Christina C. ; Obon-Santacana, Mireia ; Ose, Jennifer ; Pai, Rish K. ; Palmer, Julie R. ; Papadimitriou, Nikos ; Pardamean, Bens ; Peoples, Anita R. ; Pharoah, Paul D. P. ; Platz, Elizabeth A. ; Potter, John D. ; Rennert, Gad ; Scacheri, Peter C. ; Schoen, Robert E. ; Su, Yu-Ru ; Tangen, Catherine M. ; Thibodeau, Stephen N. ; Thomas, Duncan C. ; Ulrich, Cornelia M. ; Um, Caroline Y. ; van Duijnhoven, Franzel J. B. ; Visvanathan, Kala ; Vodicka, Pavel ; Vodickova, Ludmila ; White, Emily ; Wolk, Alicja ; Woods, Michael O. ; Qu, Conghui ; Kundaje, Anshul ; Hsu, Li ; Gauderman, W. James ; Gunter, Marc J. ; Peters, Ulrike</creator><creatorcontrib>Dimou, Niki ; Kim, Andre E. ; Flanagan, Orlagh ; Murphy, Neil ; Diez-Obrero, Virginia ; Shcherbina, Anna ; Aglago, Elom K. ; Bouras, Emmanouil ; Campbell, Peter T. ; Casey, Graham ; Gallinger, Steven ; Gruber, Stephen B. ; Jenkins, Mark A. ; Lin, Yi ; Moreno, Victor ; Ruiz-Narvaez, Edward ; Stern, Mariana C. ; Tian, Yu ; Tsilidis, Kostas K. ; Arndt, Volker ; Barry, Elizabeth L. ; Baurley, James W. ; Berndt, Sonja I. ; Bézieau, Stéphane ; Bien, Stephanie A. ; Bishop, D. Timothy ; Brenner, Hermann ; Budiarto, Arif ; Carreras-Torres, Robert ; Cenggoro, Tjeng Wawan ; Chan, Andrew T. ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Chen, Xuechen ; Conti, David V. ; Dampier, Christopher H. ; Devall, Matthew ; Drew, David A. ; Figueiredo, Jane C. ; Giles, Graham G. ; Gsur, Andrea ; Harrison, Tabitha A. ; Hidaka, Akihisa ; Hoffmeister, Michael ; Huyghe, Jeroen R. ; Jordahl, Kristina ; Kawaguchi, Eric ; Keku, Temitope O. ; Larsson, Susanna C. ; Le Marchand, Loic ; Lewinger, Juan Pablo ; Li, Li ; Mahesworo, Bharuno ; Morrison, John ; Newcomb, Polly A. ; Newton, Christina C. ; Obon-Santacana, Mireia ; Ose, Jennifer ; Pai, Rish K. ; Palmer, Julie R. ; Papadimitriou, Nikos ; Pardamean, Bens ; Peoples, Anita R. ; Pharoah, Paul D. P. ; Platz, Elizabeth A. ; Potter, John D. ; Rennert, Gad ; Scacheri, Peter C. ; Schoen, Robert E. ; Su, Yu-Ru ; Tangen, Catherine M. ; Thibodeau, Stephen N. ; Thomas, Duncan C. ; Ulrich, Cornelia M. ; Um, Caroline Y. ; van Duijnhoven, Franzel J. B. ; Visvanathan, Kala ; Vodicka, Pavel ; Vodickova, Ludmila ; White, Emily ; Wolk, Alicja ; Woods, Michael O. ; Qu, Conghui ; Kundaje, Anshul ; Hsu, Li ; Gauderman, W. James ; Gunter, Marc J. ; Peters, Ulrike</creatorcontrib><description>Background
Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis.
Methods
We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test).
Results
Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177,
SLC30A8 –
OR
AA
: 1.62, 95% CI: 1.34–1.96; OR
AG
: 1.41, 95% CI: 1.30–1.54; OR
GG
: 1.22, 95% CI: 1.13–1.31;
p
-value
3-d.f.
: 5.46 × 10
−11
) and 13q14.13 (rs9526201,
LRCH1 –
OR
GG
: 2.11, 95% CI: 1.56–2.83; OR
GA
: 1.52, 95% CI: 1.38–1.68; OR
AA
: 1.13, 95% CI: 1.06–1.21;
p
-value
2-d.f.
: 7.84 × 10
−09
).
Discussion
These results suggest that variation in genes related to insulin signaling (
SLC30A8
) and immune function (
LRCH1
) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.</description><identifier>ISSN: 0007-0920</identifier><identifier>ISSN: 1532-1827</identifier><identifier>EISSN: 1532-1827</identifier><identifier>DOI: 10.1038/s41416-023-02312-z</identifier><identifier>PMID: 37365285</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/208/68 ; 631/67/1504/1885/1393 ; Biomedical and Life Sciences ; Biomedicine ; Cancer ; Cancer Research ; Chromosome 8 ; Colorectal cancer ; Colorectal carcinoma ; Colorectal Neoplasms - genetics ; Diabetes ; Diabetes mellitus ; Diabetes Mellitus - genetics ; Drug Resistance ; Epidemiology ; Gene-Environment Interaction ; Genetic diversity ; Genetic Predisposition to Disease ; Genome-Wide Association Study - methods ; Genomes ; Humans ; Immune response ; Microfilament Proteins - genetics ; Molecular Medicine ; Oncology ; Polymorphism, Single Nucleotide ; Risk Factors</subject><ispartof>British journal of cancer, 2023-08, Vol.129 (3), p.511-520</ispartof><rights>The Author(s) 2023</rights><rights>2023. The Author(s).</rights><rights>The Author(s) 2023. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c513t-88441ae7f7aff35bfe74cf5239a5ff546281800a8ae2169b8c6589685e8dd77f3</citedby><cites>FETCH-LOGICAL-c513t-88441ae7f7aff35bfe74cf5239a5ff546281800a8ae2169b8c6589685e8dd77f3</cites><orcidid>0000-0003-1678-9328 ; 0000-0001-8786-0043 ; 0000-0001-6027-9806 ; 0000-0002-6129-1572 ; 0000-0001-5449-6230 ; 0000-0002-2818-5487 ; 0000-0001-8494-732X ; 0000-0001-5439-1500 ; 0000-0001-9320-8684 ; 0000-0003-3347-8249 ; 0000-0001-7387-6845 ; 0000-0002-8307-3197 ; 0000-0002-6534-335X ; 0000-0002-0442-3284 ; 0000-0003-3084-2287 ; 0000-0002-0339-5824 ; 0000-0002-8752-8785 ; 0000-0003-0118-0341 ; 0000-0003-1489-5506 ; 0000-0001-7284-6767 ; 0000-0003-2476-7110 ; 0000-0002-0582-8005</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/PMC10403521/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403521/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,550,723,776,780,881,27903,27904,41467,42536,51298,53770,53772</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37365285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:153463212$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Dimou, Niki</creatorcontrib><creatorcontrib>Kim, Andre E.</creatorcontrib><creatorcontrib>Flanagan, Orlagh</creatorcontrib><creatorcontrib>Murphy, Neil</creatorcontrib><creatorcontrib>Diez-Obrero, Virginia</creatorcontrib><creatorcontrib>Shcherbina, Anna</creatorcontrib><creatorcontrib>Aglago, Elom K.</creatorcontrib><creatorcontrib>Bouras, Emmanouil</creatorcontrib><creatorcontrib>Campbell, Peter T.</creatorcontrib><creatorcontrib>Casey, Graham</creatorcontrib><creatorcontrib>Gallinger, Steven</creatorcontrib><creatorcontrib>Gruber, Stephen B.</creatorcontrib><creatorcontrib>Jenkins, Mark A.</creatorcontrib><creatorcontrib>Lin, Yi</creatorcontrib><creatorcontrib>Moreno, Victor</creatorcontrib><creatorcontrib>Ruiz-Narvaez, Edward</creatorcontrib><creatorcontrib>Stern, Mariana C.</creatorcontrib><creatorcontrib>Tian, Yu</creatorcontrib><creatorcontrib>Tsilidis, Kostas K.</creatorcontrib><creatorcontrib>Arndt, Volker</creatorcontrib><creatorcontrib>Barry, Elizabeth L.</creatorcontrib><creatorcontrib>Baurley, James W.</creatorcontrib><creatorcontrib>Berndt, Sonja I.</creatorcontrib><creatorcontrib>Bézieau, Stéphane</creatorcontrib><creatorcontrib>Bien, Stephanie A.</creatorcontrib><creatorcontrib>Bishop, D. Timothy</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Budiarto, Arif</creatorcontrib><creatorcontrib>Carreras-Torres, Robert</creatorcontrib><creatorcontrib>Cenggoro, Tjeng Wawan</creatorcontrib><creatorcontrib>Chan, Andrew T.</creatorcontrib><creatorcontrib>Chang-Claude, Jenny</creatorcontrib><creatorcontrib>Chanock, Stephen J.</creatorcontrib><creatorcontrib>Chen, Xuechen</creatorcontrib><creatorcontrib>Conti, David V.</creatorcontrib><creatorcontrib>Dampier, Christopher H.</creatorcontrib><creatorcontrib>Devall, Matthew</creatorcontrib><creatorcontrib>Drew, David A.</creatorcontrib><creatorcontrib>Figueiredo, Jane C.</creatorcontrib><creatorcontrib>Giles, Graham G.</creatorcontrib><creatorcontrib>Gsur, Andrea</creatorcontrib><creatorcontrib>Harrison, Tabitha A.</creatorcontrib><creatorcontrib>Hidaka, Akihisa</creatorcontrib><creatorcontrib>Hoffmeister, Michael</creatorcontrib><creatorcontrib>Huyghe, Jeroen R.</creatorcontrib><creatorcontrib>Jordahl, Kristina</creatorcontrib><creatorcontrib>Kawaguchi, Eric</creatorcontrib><creatorcontrib>Keku, Temitope O.</creatorcontrib><creatorcontrib>Larsson, Susanna C.</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Lewinger, Juan Pablo</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Mahesworo, Bharuno</creatorcontrib><creatorcontrib>Morrison, John</creatorcontrib><creatorcontrib>Newcomb, Polly A.</creatorcontrib><creatorcontrib>Newton, Christina C.</creatorcontrib><creatorcontrib>Obon-Santacana, Mireia</creatorcontrib><creatorcontrib>Ose, Jennifer</creatorcontrib><creatorcontrib>Pai, Rish K.</creatorcontrib><creatorcontrib>Palmer, Julie R.</creatorcontrib><creatorcontrib>Papadimitriou, Nikos</creatorcontrib><creatorcontrib>Pardamean, Bens</creatorcontrib><creatorcontrib>Peoples, Anita R.</creatorcontrib><creatorcontrib>Pharoah, Paul D. P.</creatorcontrib><creatorcontrib>Platz, Elizabeth A.</creatorcontrib><creatorcontrib>Potter, John D.</creatorcontrib><creatorcontrib>Rennert, Gad</creatorcontrib><creatorcontrib>Scacheri, Peter C.</creatorcontrib><creatorcontrib>Schoen, Robert E.</creatorcontrib><creatorcontrib>Su, Yu-Ru</creatorcontrib><creatorcontrib>Tangen, Catherine M.</creatorcontrib><creatorcontrib>Thibodeau, Stephen N.</creatorcontrib><creatorcontrib>Thomas, Duncan C.</creatorcontrib><creatorcontrib>Ulrich, Cornelia M.</creatorcontrib><creatorcontrib>Um, Caroline Y.</creatorcontrib><creatorcontrib>van Duijnhoven, Franzel J. B.</creatorcontrib><creatorcontrib>Visvanathan, Kala</creatorcontrib><creatorcontrib>Vodicka, Pavel</creatorcontrib><creatorcontrib>Vodickova, Ludmila</creatorcontrib><creatorcontrib>White, Emily</creatorcontrib><creatorcontrib>Wolk, Alicja</creatorcontrib><creatorcontrib>Woods, Michael O.</creatorcontrib><creatorcontrib>Qu, Conghui</creatorcontrib><creatorcontrib>Kundaje, Anshul</creatorcontrib><creatorcontrib>Hsu, Li</creatorcontrib><creatorcontrib>Gauderman, W. James</creatorcontrib><creatorcontrib>Gunter, Marc J.</creatorcontrib><creatorcontrib>Peters, Ulrike</creatorcontrib><title>Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses</title><title>British journal of cancer</title><addtitle>Br J Cancer</addtitle><addtitle>Br J Cancer</addtitle><description>Background
Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis.
Methods
We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test).
Results
Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177,
SLC30A8 –
OR
AA
: 1.62, 95% CI: 1.34–1.96; OR
AG
: 1.41, 95% CI: 1.30–1.54; OR
GG
: 1.22, 95% CI: 1.13–1.31;
p
-value
3-d.f.
: 5.46 × 10
−11
) and 13q14.13 (rs9526201,
LRCH1 –
OR
GG
: 2.11, 95% CI: 1.56–2.83; OR
GA
: 1.52, 95% CI: 1.38–1.68; OR
AA
: 1.13, 95% CI: 1.06–1.21;
p
-value
2-d.f.
: 7.84 × 10
−09
).
Discussion
These results suggest that variation in genes related to insulin signaling (
SLC30A8
) and immune function (
LRCH1
) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.</description><subject>631/208/68</subject><subject>631/67/1504/1885/1393</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Chromosome 8</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Diabetes</subject><subject>Diabetes mellitus</subject><subject>Diabetes Mellitus - genetics</subject><subject>Drug Resistance</subject><subject>Epidemiology</subject><subject>Gene-Environment Interaction</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Humans</subject><subject>Immune response</subject><subject>Microfilament Proteins - genetics</subject><subject>Molecular Medicine</subject><subject>Oncology</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Factors</subject><issn>0007-0920</issn><issn>1532-1827</issn><issn>1532-1827</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>D8T</sourceid><recordid>eNp9kbtuFDEUhi0EIkvgBSiQJRqaAV_HngqhiJsUCQqoLY_neNdh1l7smURJxTvkDfMkeNglEAoKy5fz_b-P_SP0lJKXlHD9qggqaNsQxpdBWXN1D62o5Kyhmqn7aEUIUQ3pGDlCj0o5q9uOaPUQHXHFW8m0XKH155z6ENd42gAegu1hgoJtHLBLY8rgJjtiZ6ODjDOMdgoplk3Y4bksqjVEwDc_rjHE85BT3EKccIgTZOsWtDrZ8bJAeYweeDsWeHKYj9HXd2-_nHxoTj-9_3jy5rRxkvKp0VoIakF5Zb3nsveghPOS8c5K76VomaaaEKstMNp2vXat1F2rJehhUMrzY9TsfcsF7Obe7HLY2nxpkg3mcPStrsAIIaXQlX-952tlC4Or_Wc73pHdrcSwMet0bigRhEtGq8OLg0NO32cok9mG4mAcbYQ0F8M0JxXjWlT0-T_oWZpz_aGFErJTmmhZKbanXE6lZPC33VBiluDNPnhTQze_gjdXVfTs73fcSn4nXQF--JhaimvIf-7-j-1PAo69Hw</recordid><startdate>20230824</startdate><enddate>20230824</enddate><creator>Dimou, Niki</creator><creator>Kim, Andre E.</creator><creator>Flanagan, Orlagh</creator><creator>Murphy, Neil</creator><creator>Diez-Obrero, Virginia</creator><creator>Shcherbina, Anna</creator><creator>Aglago, Elom K.</creator><creator>Bouras, Emmanouil</creator><creator>Campbell, Peter T.</creator><creator>Casey, Graham</creator><creator>Gallinger, Steven</creator><creator>Gruber, Stephen B.</creator><creator>Jenkins, Mark A.</creator><creator>Lin, Yi</creator><creator>Moreno, Victor</creator><creator>Ruiz-Narvaez, Edward</creator><creator>Stern, Mariana C.</creator><creator>Tian, Yu</creator><creator>Tsilidis, Kostas K.</creator><creator>Arndt, Volker</creator><creator>Barry, Elizabeth L.</creator><creator>Baurley, James W.</creator><creator>Berndt, Sonja I.</creator><creator>Bézieau, Stéphane</creator><creator>Bien, Stephanie A.</creator><creator>Bishop, D. Timothy</creator><creator>Brenner, Hermann</creator><creator>Budiarto, Arif</creator><creator>Carreras-Torres, Robert</creator><creator>Cenggoro, Tjeng Wawan</creator><creator>Chan, Andrew T.</creator><creator>Chang-Claude, Jenny</creator><creator>Chanock, Stephen J.</creator><creator>Chen, Xuechen</creator><creator>Conti, David V.</creator><creator>Dampier, Christopher H.</creator><creator>Devall, Matthew</creator><creator>Drew, David A.</creator><creator>Figueiredo, Jane C.</creator><creator>Giles, Graham G.</creator><creator>Gsur, Andrea</creator><creator>Harrison, Tabitha A.</creator><creator>Hidaka, Akihisa</creator><creator>Hoffmeister, Michael</creator><creator>Huyghe, Jeroen R.</creator><creator>Jordahl, Kristina</creator><creator>Kawaguchi, Eric</creator><creator>Keku, Temitope O.</creator><creator>Larsson, Susanna C.</creator><creator>Le Marchand, Loic</creator><creator>Lewinger, Juan Pablo</creator><creator>Li, Li</creator><creator>Mahesworo, Bharuno</creator><creator>Morrison, John</creator><creator>Newcomb, Polly A.</creator><creator>Newton, Christina C.</creator><creator>Obon-Santacana, Mireia</creator><creator>Ose, Jennifer</creator><creator>Pai, Rish K.</creator><creator>Palmer, Julie R.</creator><creator>Papadimitriou, Nikos</creator><creator>Pardamean, Bens</creator><creator>Peoples, Anita R.</creator><creator>Pharoah, Paul D. P.</creator><creator>Platz, Elizabeth A.</creator><creator>Potter, John D.</creator><creator>Rennert, Gad</creator><creator>Scacheri, Peter C.</creator><creator>Schoen, Robert E.</creator><creator>Su, Yu-Ru</creator><creator>Tangen, Catherine M.</creator><creator>Thibodeau, Stephen N.</creator><creator>Thomas, Duncan C.</creator><creator>Ulrich, Cornelia M.</creator><creator>Um, Caroline Y.</creator><creator>van Duijnhoven, Franzel J. B.</creator><creator>Visvanathan, Kala</creator><creator>Vodicka, Pavel</creator><creator>Vodickova, Ludmila</creator><creator>White, Emily</creator><creator>Wolk, Alicja</creator><creator>Woods, Michael O.</creator><creator>Qu, Conghui</creator><creator>Kundaje, Anshul</creator><creator>Hsu, Li</creator><creator>Gauderman, W. James</creator><creator>Gunter, Marc J.</creator><creator>Peters, Ulrike</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7RV</scope><scope>7TO</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>7X8</scope><scope>5PM</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>D8T</scope><scope>ZZAVC</scope><orcidid>https://orcid.org/0000-0003-1678-9328</orcidid><orcidid>https://orcid.org/0000-0001-8786-0043</orcidid><orcidid>https://orcid.org/0000-0001-6027-9806</orcidid><orcidid>https://orcid.org/0000-0002-6129-1572</orcidid><orcidid>https://orcid.org/0000-0001-5449-6230</orcidid><orcidid>https://orcid.org/0000-0002-2818-5487</orcidid><orcidid>https://orcid.org/0000-0001-8494-732X</orcidid><orcidid>https://orcid.org/0000-0001-5439-1500</orcidid><orcidid>https://orcid.org/0000-0001-9320-8684</orcidid><orcidid>https://orcid.org/0000-0003-3347-8249</orcidid><orcidid>https://orcid.org/0000-0001-7387-6845</orcidid><orcidid>https://orcid.org/0000-0002-8307-3197</orcidid><orcidid>https://orcid.org/0000-0002-6534-335X</orcidid><orcidid>https://orcid.org/0000-0002-0442-3284</orcidid><orcidid>https://orcid.org/0000-0003-3084-2287</orcidid><orcidid>https://orcid.org/0000-0002-0339-5824</orcidid><orcidid>https://orcid.org/0000-0002-8752-8785</orcidid><orcidid>https://orcid.org/0000-0003-0118-0341</orcidid><orcidid>https://orcid.org/0000-0003-1489-5506</orcidid><orcidid>https://orcid.org/0000-0001-7284-6767</orcidid><orcidid>https://orcid.org/0000-0003-2476-7110</orcidid><orcidid>https://orcid.org/0000-0002-0582-8005</orcidid></search><sort><creationdate>20230824</creationdate><title>Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses</title><author>Dimou, Niki ; Kim, Andre E. ; Flanagan, Orlagh ; Murphy, Neil ; Diez-Obrero, Virginia ; Shcherbina, Anna ; Aglago, Elom K. ; Bouras, Emmanouil ; Campbell, Peter T. ; Casey, Graham ; Gallinger, Steven ; Gruber, Stephen B. ; Jenkins, Mark A. ; Lin, Yi ; Moreno, Victor ; Ruiz-Narvaez, Edward ; Stern, Mariana C. ; Tian, Yu ; Tsilidis, Kostas K. ; Arndt, Volker ; Barry, Elizabeth L. ; Baurley, James W. ; Berndt, Sonja I. ; Bézieau, Stéphane ; Bien, Stephanie A. ; Bishop, D. Timothy ; Brenner, Hermann ; Budiarto, Arif ; Carreras-Torres, Robert ; Cenggoro, Tjeng Wawan ; Chan, Andrew T. ; Chang-Claude, Jenny ; Chanock, Stephen J. ; Chen, Xuechen ; Conti, David V. ; Dampier, Christopher H. ; Devall, Matthew ; Drew, David A. ; Figueiredo, Jane C. ; Giles, Graham G. ; Gsur, Andrea ; Harrison, Tabitha A. ; Hidaka, Akihisa ; Hoffmeister, Michael ; Huyghe, Jeroen R. ; Jordahl, Kristina ; Kawaguchi, Eric ; Keku, Temitope O. ; Larsson, Susanna C. ; Le Marchand, Loic ; Lewinger, Juan Pablo ; Li, Li ; Mahesworo, Bharuno ; Morrison, John ; Newcomb, Polly A. ; Newton, Christina C. ; Obon-Santacana, Mireia ; Ose, Jennifer ; Pai, Rish K. ; Palmer, Julie R. ; Papadimitriou, Nikos ; Pardamean, Bens ; Peoples, Anita R. ; Pharoah, Paul D. P. ; Platz, Elizabeth A. ; Potter, John D. ; Rennert, Gad ; Scacheri, Peter C. ; Schoen, Robert E. ; Su, Yu-Ru ; Tangen, Catherine M. ; Thibodeau, Stephen N. ; Thomas, Duncan C. ; Ulrich, Cornelia M. ; Um, Caroline Y. ; van Duijnhoven, Franzel J. B. ; Visvanathan, Kala ; Vodicka, Pavel ; Vodickova, Ludmila ; White, Emily ; Wolk, Alicja ; Woods, Michael O. ; Qu, Conghui ; Kundaje, Anshul ; Hsu, Li ; Gauderman, W. James ; Gunter, Marc J. ; Peters, Ulrike</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c513t-88441ae7f7aff35bfe74cf5239a5ff546281800a8ae2169b8c6589685e8dd77f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>631/208/68</topic><topic>631/67/1504/1885/1393</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer</topic><topic>Cancer Research</topic><topic>Chromosome 8</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Diabetes</topic><topic>Diabetes mellitus</topic><topic>Diabetes Mellitus - genetics</topic><topic>Drug Resistance</topic><topic>Epidemiology</topic><topic>Gene-Environment Interaction</topic><topic>Genetic diversity</topic><topic>Genetic Predisposition to Disease</topic><topic>Genome-Wide Association Study - methods</topic><topic>Genomes</topic><topic>Humans</topic><topic>Immune response</topic><topic>Microfilament Proteins - genetics</topic><topic>Molecular Medicine</topic><topic>Oncology</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dimou, Niki</creatorcontrib><creatorcontrib>Kim, Andre E.</creatorcontrib><creatorcontrib>Flanagan, Orlagh</creatorcontrib><creatorcontrib>Murphy, Neil</creatorcontrib><creatorcontrib>Diez-Obrero, Virginia</creatorcontrib><creatorcontrib>Shcherbina, Anna</creatorcontrib><creatorcontrib>Aglago, Elom K.</creatorcontrib><creatorcontrib>Bouras, Emmanouil</creatorcontrib><creatorcontrib>Campbell, Peter T.</creatorcontrib><creatorcontrib>Casey, Graham</creatorcontrib><creatorcontrib>Gallinger, Steven</creatorcontrib><creatorcontrib>Gruber, Stephen B.</creatorcontrib><creatorcontrib>Jenkins, Mark A.</creatorcontrib><creatorcontrib>Lin, Yi</creatorcontrib><creatorcontrib>Moreno, Victor</creatorcontrib><creatorcontrib>Ruiz-Narvaez, Edward</creatorcontrib><creatorcontrib>Stern, Mariana C.</creatorcontrib><creatorcontrib>Tian, Yu</creatorcontrib><creatorcontrib>Tsilidis, Kostas K.</creatorcontrib><creatorcontrib>Arndt, Volker</creatorcontrib><creatorcontrib>Barry, Elizabeth L.</creatorcontrib><creatorcontrib>Baurley, James W.</creatorcontrib><creatorcontrib>Berndt, Sonja I.</creatorcontrib><creatorcontrib>Bézieau, Stéphane</creatorcontrib><creatorcontrib>Bien, Stephanie A.</creatorcontrib><creatorcontrib>Bishop, D. Timothy</creatorcontrib><creatorcontrib>Brenner, Hermann</creatorcontrib><creatorcontrib>Budiarto, Arif</creatorcontrib><creatorcontrib>Carreras-Torres, Robert</creatorcontrib><creatorcontrib>Cenggoro, Tjeng Wawan</creatorcontrib><creatorcontrib>Chan, Andrew T.</creatorcontrib><creatorcontrib>Chang-Claude, Jenny</creatorcontrib><creatorcontrib>Chanock, Stephen J.</creatorcontrib><creatorcontrib>Chen, Xuechen</creatorcontrib><creatorcontrib>Conti, David V.</creatorcontrib><creatorcontrib>Dampier, Christopher H.</creatorcontrib><creatorcontrib>Devall, Matthew</creatorcontrib><creatorcontrib>Drew, David A.</creatorcontrib><creatorcontrib>Figueiredo, Jane C.</creatorcontrib><creatorcontrib>Giles, Graham G.</creatorcontrib><creatorcontrib>Gsur, Andrea</creatorcontrib><creatorcontrib>Harrison, Tabitha A.</creatorcontrib><creatorcontrib>Hidaka, Akihisa</creatorcontrib><creatorcontrib>Hoffmeister, Michael</creatorcontrib><creatorcontrib>Huyghe, Jeroen R.</creatorcontrib><creatorcontrib>Jordahl, Kristina</creatorcontrib><creatorcontrib>Kawaguchi, Eric</creatorcontrib><creatorcontrib>Keku, Temitope O.</creatorcontrib><creatorcontrib>Larsson, Susanna C.</creatorcontrib><creatorcontrib>Le Marchand, Loic</creatorcontrib><creatorcontrib>Lewinger, Juan Pablo</creatorcontrib><creatorcontrib>Li, Li</creatorcontrib><creatorcontrib>Mahesworo, Bharuno</creatorcontrib><creatorcontrib>Morrison, John</creatorcontrib><creatorcontrib>Newcomb, Polly A.</creatorcontrib><creatorcontrib>Newton, Christina C.</creatorcontrib><creatorcontrib>Obon-Santacana, Mireia</creatorcontrib><creatorcontrib>Ose, Jennifer</creatorcontrib><creatorcontrib>Pai, Rish K.</creatorcontrib><creatorcontrib>Palmer, Julie R.</creatorcontrib><creatorcontrib>Papadimitriou, Nikos</creatorcontrib><creatorcontrib>Pardamean, Bens</creatorcontrib><creatorcontrib>Peoples, Anita R.</creatorcontrib><creatorcontrib>Pharoah, Paul D. P.</creatorcontrib><creatorcontrib>Platz, Elizabeth A.</creatorcontrib><creatorcontrib>Potter, John D.</creatorcontrib><creatorcontrib>Rennert, Gad</creatorcontrib><creatorcontrib>Scacheri, Peter C.</creatorcontrib><creatorcontrib>Schoen, Robert E.</creatorcontrib><creatorcontrib>Su, Yu-Ru</creatorcontrib><creatorcontrib>Tangen, Catherine M.</creatorcontrib><creatorcontrib>Thibodeau, Stephen N.</creatorcontrib><creatorcontrib>Thomas, Duncan C.</creatorcontrib><creatorcontrib>Ulrich, Cornelia M.</creatorcontrib><creatorcontrib>Um, Caroline Y.</creatorcontrib><creatorcontrib>van Duijnhoven, Franzel J. B.</creatorcontrib><creatorcontrib>Visvanathan, Kala</creatorcontrib><creatorcontrib>Vodicka, Pavel</creatorcontrib><creatorcontrib>Vodickova, Ludmila</creatorcontrib><creatorcontrib>White, Emily</creatorcontrib><creatorcontrib>Wolk, Alicja</creatorcontrib><creatorcontrib>Woods, Michael O.</creatorcontrib><creatorcontrib>Qu, Conghui</creatorcontrib><creatorcontrib>Kundaje, Anshul</creatorcontrib><creatorcontrib>Hsu, Li</creatorcontrib><creatorcontrib>Gauderman, W. James</creatorcontrib><creatorcontrib>Gunter, Marc J.</creatorcontrib><creatorcontrib>Peters, Ulrike</creatorcontrib><collection>SpringerOpen</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>ProQuest Nursing and Allied Health Journals</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>ProQuest Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest Central UK/Ireland</collection><collection>British Nursing Database</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SwePub Articles full text</collection><jtitle>British journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dimou, Niki</au><au>Kim, Andre E.</au><au>Flanagan, Orlagh</au><au>Murphy, Neil</au><au>Diez-Obrero, Virginia</au><au>Shcherbina, Anna</au><au>Aglago, Elom K.</au><au>Bouras, Emmanouil</au><au>Campbell, Peter T.</au><au>Casey, Graham</au><au>Gallinger, Steven</au><au>Gruber, Stephen B.</au><au>Jenkins, Mark A.</au><au>Lin, Yi</au><au>Moreno, Victor</au><au>Ruiz-Narvaez, Edward</au><au>Stern, Mariana C.</au><au>Tian, Yu</au><au>Tsilidis, Kostas K.</au><au>Arndt, Volker</au><au>Barry, Elizabeth L.</au><au>Baurley, James W.</au><au>Berndt, Sonja I.</au><au>Bézieau, Stéphane</au><au>Bien, Stephanie A.</au><au>Bishop, D. Timothy</au><au>Brenner, Hermann</au><au>Budiarto, Arif</au><au>Carreras-Torres, Robert</au><au>Cenggoro, Tjeng Wawan</au><au>Chan, Andrew T.</au><au>Chang-Claude, Jenny</au><au>Chanock, Stephen J.</au><au>Chen, Xuechen</au><au>Conti, David V.</au><au>Dampier, Christopher H.</au><au>Devall, Matthew</au><au>Drew, David A.</au><au>Figueiredo, Jane C.</au><au>Giles, Graham G.</au><au>Gsur, Andrea</au><au>Harrison, Tabitha A.</au><au>Hidaka, Akihisa</au><au>Hoffmeister, Michael</au><au>Huyghe, Jeroen R.</au><au>Jordahl, Kristina</au><au>Kawaguchi, Eric</au><au>Keku, Temitope O.</au><au>Larsson, Susanna C.</au><au>Le Marchand, Loic</au><au>Lewinger, Juan Pablo</au><au>Li, Li</au><au>Mahesworo, Bharuno</au><au>Morrison, John</au><au>Newcomb, Polly A.</au><au>Newton, Christina C.</au><au>Obon-Santacana, Mireia</au><au>Ose, Jennifer</au><au>Pai, Rish K.</au><au>Palmer, Julie R.</au><au>Papadimitriou, Nikos</au><au>Pardamean, Bens</au><au>Peoples, Anita R.</au><au>Pharoah, Paul D. P.</au><au>Platz, Elizabeth A.</au><au>Potter, John D.</au><au>Rennert, Gad</au><au>Scacheri, Peter C.</au><au>Schoen, Robert E.</au><au>Su, Yu-Ru</au><au>Tangen, Catherine M.</au><au>Thibodeau, Stephen N.</au><au>Thomas, Duncan C.</au><au>Ulrich, Cornelia M.</au><au>Um, Caroline Y.</au><au>van Duijnhoven, Franzel J. B.</au><au>Visvanathan, Kala</au><au>Vodicka, Pavel</au><au>Vodickova, Ludmila</au><au>White, Emily</au><au>Wolk, Alicja</au><au>Woods, Michael O.</au><au>Qu, Conghui</au><au>Kundaje, Anshul</au><au>Hsu, Li</au><au>Gauderman, W. James</au><au>Gunter, Marc J.</au><au>Peters, Ulrike</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses</atitle><jtitle>British journal of cancer</jtitle><stitle>Br J Cancer</stitle><addtitle>Br J Cancer</addtitle><date>2023-08-24</date><risdate>2023</risdate><volume>129</volume><issue>3</issue><spage>511</spage><epage>520</epage><pages>511-520</pages><issn>0007-0920</issn><issn>1532-1827</issn><eissn>1532-1827</eissn><abstract>Background
Diabetes is an established risk factor for colorectal cancer. However, the mechanisms underlying this relationship still require investigation and it is not known if the association is modified by genetic variants. To address these questions, we undertook a genome-wide gene-environment interaction analysis.
Methods
We used data from 3 genetic consortia (CCFR, CORECT, GECCO; 31,318 colorectal cancer cases/41,499 controls) and undertook genome-wide gene-environment interaction analyses with colorectal cancer risk, including interaction tests of genetics(G)xdiabetes (1-degree of freedom; d.f.) and joint testing of Gxdiabetes, G-colorectal cancer association (2-d.f. joint test) and G-diabetes correlation (3-d.f. joint test).
Results
Based on the joint tests, we found that the association of diabetes with colorectal cancer risk is modified by loci on chromosomes 8q24.11 (rs3802177,
SLC30A8 –
OR
AA
: 1.62, 95% CI: 1.34–1.96; OR
AG
: 1.41, 95% CI: 1.30–1.54; OR
GG
: 1.22, 95% CI: 1.13–1.31;
p
-value
3-d.f.
: 5.46 × 10
−11
) and 13q14.13 (rs9526201,
LRCH1 –
OR
GG
: 2.11, 95% CI: 1.56–2.83; OR
GA
: 1.52, 95% CI: 1.38–1.68; OR
AA
: 1.13, 95% CI: 1.06–1.21;
p
-value
2-d.f.
: 7.84 × 10
−09
).
Discussion
These results suggest that variation in genes related to insulin signaling (
SLC30A8
) and immune function (
LRCH1
) may modify the association of diabetes with colorectal cancer risk and provide novel insights into the biology underlying the diabetes and colorectal cancer relationship.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>37365285</pmid><doi>10.1038/s41416-023-02312-z</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0003-1678-9328</orcidid><orcidid>https://orcid.org/0000-0001-8786-0043</orcidid><orcidid>https://orcid.org/0000-0001-6027-9806</orcidid><orcidid>https://orcid.org/0000-0002-6129-1572</orcidid><orcidid>https://orcid.org/0000-0001-5449-6230</orcidid><orcidid>https://orcid.org/0000-0002-2818-5487</orcidid><orcidid>https://orcid.org/0000-0001-8494-732X</orcidid><orcidid>https://orcid.org/0000-0001-5439-1500</orcidid><orcidid>https://orcid.org/0000-0001-9320-8684</orcidid><orcidid>https://orcid.org/0000-0003-3347-8249</orcidid><orcidid>https://orcid.org/0000-0001-7387-6845</orcidid><orcidid>https://orcid.org/0000-0002-8307-3197</orcidid><orcidid>https://orcid.org/0000-0002-6534-335X</orcidid><orcidid>https://orcid.org/0000-0002-0442-3284</orcidid><orcidid>https://orcid.org/0000-0003-3084-2287</orcidid><orcidid>https://orcid.org/0000-0002-0339-5824</orcidid><orcidid>https://orcid.org/0000-0002-8752-8785</orcidid><orcidid>https://orcid.org/0000-0003-0118-0341</orcidid><orcidid>https://orcid.org/0000-0003-1489-5506</orcidid><orcidid>https://orcid.org/0000-0001-7284-6767</orcidid><orcidid>https://orcid.org/0000-0003-2476-7110</orcidid><orcidid>https://orcid.org/0000-0002-0582-8005</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0007-0920 |
| ispartof | British journal of cancer, 2023-08, Vol.129 (3), p.511-520 |
| issn | 0007-0920 1532-1827 1532-1827 |
| language | eng |
| recordid | cdi_swepub_primary_oai_swepub_ki_se_445548 |
| source | PubMed (Medline); MEDLINE; SWEPUB Freely available online; EZB Electronic Journals Library; SpringerLink Journals - AutoHoldings |
| subjects | 631/208/68 631/67/1504/1885/1393 Biomedical and Life Sciences Biomedicine Cancer Cancer Research Chromosome 8 Colorectal cancer Colorectal carcinoma Colorectal Neoplasms - genetics Diabetes Diabetes mellitus Diabetes Mellitus - genetics Drug Resistance Epidemiology Gene-Environment Interaction Genetic diversity Genetic Predisposition to Disease Genome-Wide Association Study - methods Genomes Humans Immune response Microfilament Proteins - genetics Molecular Medicine Oncology Polymorphism, Single Nucleotide Risk Factors |
| title | Probing the diabetes and colorectal cancer relationship using gene – environment interaction analyses |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-22T17%3A55%3A42IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_swepu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Probing%20the%20diabetes%20and%20colorectal%20cancer%20relationship%20using%20gene%20%E2%80%93%20environment%20interaction%20analyses&rft.jtitle=British%20journal%20of%20cancer&rft.au=Dimou,%20Niki&rft.date=2023-08-24&rft.volume=129&rft.issue=3&rft.spage=511&rft.epage=520&rft.pages=511-520&rft.issn=0007-0920&rft.eissn=1532-1827&rft_id=info:doi/10.1038/s41416-023-02312-z&rft_dat=%3Cproquest_swepu%3E2830213384%3C/proquest_swepu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2845978085&rft_id=info:pmid/37365285&rfr_iscdi=true |