Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis
Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytoki...
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| Veröffentlicht in: | International journal of cancer 2024-07, Vol.155 (1), p.159-171 |
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| container_title | International journal of cancer |
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| creator | Meng, Cong Sun, Liting Shi, Jinyao Li, Yang Gao, Jiale Liu, Yishan Wei, Pengyu Yang, Zhengyang Yao, Hongwei Zhang, Zhongtao |
| description | Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p |
| doi_str_mv | 10.1002/ijc.34891 |
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). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.</description><identifier>ISSN: 0020-7136</identifier><identifier>EISSN: 1097-0215</identifier><identifier>DOI: 10.1002/ijc.34891</identifier><identifier>PMID: 38385833</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Cancer ; Colorectal cancer ; Colorectal carcinoma ; Cytokines ; Digestive system diseases ; Genetic analysis ; Genetic diversity ; Genomes ; Health risks ; Macrophages ; Mortality ; Vascular endothelial growth factor</subject><ispartof>International journal of cancer, 2024-07, Vol.155 (1), p.159-171</ispartof><rights>2024 UICC.</rights><rights>2024 UICC</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c273t-f94a60761fcb87e1f28f1f7159826f25f7a4997b08b617cc6b493391287e33d03</cites><orcidid>0000-0003-1307-8387 ; 0000-0002-2640-9619</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38385833$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Meng, Cong</creatorcontrib><creatorcontrib>Sun, Liting</creatorcontrib><creatorcontrib>Shi, Jinyao</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Gao, Jiale</creatorcontrib><creatorcontrib>Liu, Yishan</creatorcontrib><creatorcontrib>Wei, Pengyu</creatorcontrib><creatorcontrib>Yang, Zhengyang</creatorcontrib><creatorcontrib>Yao, Hongwei</creatorcontrib><creatorcontrib>Zhang, Zhongtao</creatorcontrib><title>Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis</title><title>International journal of cancer</title><addtitle>Int J Cancer</addtitle><description>Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10
). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.</description><subject>Cancer</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Cytokines</subject><subject>Digestive system diseases</subject><subject>Genetic analysis</subject><subject>Genetic diversity</subject><subject>Genomes</subject><subject>Health risks</subject><subject>Macrophages</subject><subject>Mortality</subject><subject>Vascular endothelial growth factor</subject><issn>0020-7136</issn><issn>1097-0215</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><recordid>eNpdkT1PHDEQhi0EggtJwR9AlmiSYmFs767tdAiRD4mIJqlXXt8Y-fDZF3uX5FLzw-PjI0WqkWaeeTSal5ATBucMgF_4lT0XrdJsjywYaNkAZ90-WdQZNJKJ_oi8KWUFwFgH7SE5EkqoTgmxII_XvzchZR_vqDVzMYHalDMGM_kUCx1x-oUYqfXZzrtm5QI-YCg0OWq3U7r3EQs1cVkXqwjttHOYaDHT7Mv9R3pJv2FcYvAm0lzBtPZ_nvR1y4Rt8eUtOXAmFHz3Uo_Jj0_X36--NDe3n79eXd40lksxNU63pgfZM2dHJZE5rhxzknVa8d7xzknTai1HUGPPpLX92GohNOMVFmIJ4pi8f_Zucvo5Y5mGtS8WQzAR01wGrgW0kvegKnr2H7pKc673lkFAVx8JkrWV-vBM2ZxKyeiGTfZrk7cDg2EXzVCjGZ6iqezpi3Ee17j8R75mIf4CQ_yKpg</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>Meng, Cong</creator><creator>Sun, Liting</creator><creator>Shi, Jinyao</creator><creator>Li, Yang</creator><creator>Gao, Jiale</creator><creator>Liu, Yishan</creator><creator>Wei, Pengyu</creator><creator>Yang, Zhengyang</creator><creator>Yao, Hongwei</creator><creator>Zhang, Zhongtao</creator><general>Wiley Subscription Services, Inc</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TO</scope><scope>7U9</scope><scope>H94</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0003-1307-8387</orcidid><orcidid>https://orcid.org/0000-0002-2640-9619</orcidid></search><sort><creationdate>20240701</creationdate><title>Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis</title><author>Meng, Cong ; Sun, Liting ; Shi, Jinyao ; Li, Yang ; Gao, Jiale ; Liu, Yishan ; Wei, Pengyu ; Yang, Zhengyang ; Yao, Hongwei ; Zhang, Zhongtao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c273t-f94a60761fcb87e1f28f1f7159826f25f7a4997b08b617cc6b493391287e33d03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Cancer</topic><topic>Colorectal cancer</topic><topic>Colorectal carcinoma</topic><topic>Cytokines</topic><topic>Digestive system diseases</topic><topic>Genetic analysis</topic><topic>Genetic diversity</topic><topic>Genomes</topic><topic>Health risks</topic><topic>Macrophages</topic><topic>Mortality</topic><topic>Vascular endothelial growth factor</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Meng, Cong</creatorcontrib><creatorcontrib>Sun, Liting</creatorcontrib><creatorcontrib>Shi, Jinyao</creatorcontrib><creatorcontrib>Li, Yang</creatorcontrib><creatorcontrib>Gao, Jiale</creatorcontrib><creatorcontrib>Liu, Yishan</creatorcontrib><creatorcontrib>Wei, Pengyu</creatorcontrib><creatorcontrib>Yang, Zhengyang</creatorcontrib><creatorcontrib>Yao, Hongwei</creatorcontrib><creatorcontrib>Zhang, Zhongtao</creatorcontrib><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>International journal of cancer</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Meng, Cong</au><au>Sun, Liting</au><au>Shi, Jinyao</au><au>Li, Yang</au><au>Gao, Jiale</au><au>Liu, Yishan</au><au>Wei, Pengyu</au><au>Yang, Zhengyang</au><au>Yao, Hongwei</au><au>Zhang, Zhongtao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis</atitle><jtitle>International journal of cancer</jtitle><addtitle>Int J Cancer</addtitle><date>2024-07-01</date><risdate>2024</risdate><volume>155</volume><issue>1</issue><spage>159</spage><epage>171</epage><pages>159-171</pages><issn>0020-7136</issn><eissn>1097-0215</eissn><abstract>Colorectal cancer has the highest mortality rate of all digestive system diseases. Considering the debate about cytokines and biases that exist in traditional observational study designs, we performed a two-sample Mendelian randomization (MR) analysis to explore the association of circulating cytokines with CRC risk. In this study, we used cytokine genetic variants from a recently published genome-wide association study (GWAS) including 14,824 European-ancestry participants. Summary-level data for colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium. In addition, we conducted independent supplementary analyses using genetic variation data of colorectal cancer and cytokines from a large public GWAS in 2021. Among 91 circulating factors, we only found IL-12B to be significantly associated with CRC risk (odds ratio [OR]: 1.19; 95% confidence interval [CI]: 1.00-1.42; p = .046). We used 2021 data for analysis and found that higher Interleukin-12p70 levels (IL-12p70) were revealed to have a significant positive association with CRC risk (OR: 1.27; 95% CI: 1.13-1.43; p < 1.22 × 10
). Moreover, CRC was suggestively correlated with an elevated level of vascular endothelial growth factor (VEGF) (OR: 1.17; 95% CI: 1.02-1.35; p = .026), macrophage colony-stimulating factor (M-CSF) (OR: 0.85; 95% CI: 0.76-0.96; p = .005), IL-13 (OR: 1.15; 95% CI: 1.02-1.30; p = .028), IL-10 (OR: 1.23; 95% CI: 1.01-1.49; p = .037), and IL-7 (OR: 1.19; 95% CI: 1.02-1.39; p = .024). Our MR studies support that one cytokine IL-12 is significantly associated with CRC risk and that five cytokines VEGF, M-CSF, IL-13, IL-10, and IL-7 are associated with CRC risk.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>38385833</pmid><doi>10.1002/ijc.34891</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-1307-8387</orcidid><orcidid>https://orcid.org/0000-0002-2640-9619</orcidid></addata></record> |
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| subjects | Cancer Colorectal cancer Colorectal carcinoma Cytokines Digestive system diseases Genetic analysis Genetic diversity Genomes Health risks Macrophages Mortality Vascular endothelial growth factor |
| title | Exploring causal correlations between circulating levels of cytokines and colorectal cancer risk: A Mendelian randomization analysis |
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