Emma Hazelwood, Catalina Lopez Manzano, Emma E Vincent, Demetrius Albanes, D Timothy Bishop, Loïc Le Marchand, Cornelia M Ulrich, Ulrike Peters, Gwen Murphy, N Jewel Samadder, Laura Anderson, Marc J Gunter, Neil Murphy, Bethany Van Guelpen, Nikos Papadimitriou
{"title":"血浆胃泌素与性别特异性、部位特异性和早发性结直肠癌的风险：孟德尔随机分析","authors":"Emma Hazelwood, Catalina Lopez Manzano, Emma E Vincent, Demetrius Albanes, D Timothy Bishop, Loïc Le Marchand, Cornelia M Ulrich, Ulrike Peters, Gwen Murphy, N Jewel Samadder, Laura Anderson, Marc J Gunter, Neil Murphy, Bethany Van Guelpen, Nikos Papadimitriou","doi":"10.1158/1055-9965.EPI-24-0926","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis.</p><p><strong>Methods: </strong>Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied.</p><p><strong>Results: </strong>We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC.</p><p><strong>Conclusions: </strong>Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk.</p><p><strong>Impact: </strong>This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.\",\"authors\":\"Emma Hazelwood, Catalina Lopez Manzano, Emma E Vincent, Demetrius Albanes, D Timothy Bishop, Loïc Le Marchand, Cornelia M Ulrich, Ulrike Peters, Gwen Murphy, N Jewel Samadder, Laura Anderson, Marc J Gunter, Neil Murphy, Bethany Van Guelpen, Nikos Papadimitriou\",\"doi\":\"10.1158/1055-9965.EPI-24-0926\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis.</p><p><strong>Methods: </strong>Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied.</p><p><strong>Results: </strong>We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC.</p><p><strong>Conclusions: </strong>Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk.</p><p><strong>Impact: </strong>This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.</p>\",\"PeriodicalId\":9458,\"journal\":{\"name\":\"Cancer Epidemiology Biomarkers & Prevention\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-10-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Epidemiology Biomarkers & Prevention\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1055-9965.EPI-24-0926\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Epidemiology Biomarkers & Prevention","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1055-9965.EPI-24-0926","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Plasma ghrelin and risks of sex-specific, site-specific, and early-onset colorectal cancer: A Mendelian randomization analysis.
Background: Epidemiological and laboratory-based studies have provided conflicting evidence for a role of ghrelin in colorectal cancer (CRC) development. We conducted two-sample Mendelian randomization (MR) analyses to evaluate evidence for an association of circulating ghrelin and CRC risk overall and by sex, cancer subsite and age at diagnosis.
Methods: Genetic instruments proxying plasma total ghrelin levels were obtained from a recent genome-wide association study of 54,219 participants. Summary data for CRC risk were obtained from a recent meta-analysis of several genetic consortia (up to 73,673 cases and 86,854 controls). A two-sample MR approach and several sensitivity analyses were applied.
Results: We found no evidence for an association of genetically-predicted plasma total ghrelin levels and CRC risk (0.95, 95% confidence interval: 0.81-1.12; R2 of ghrelin genetic instruments: 4.6%), with similarly null results observed when stratified by sex, anatomical subsite, and for early-onset CRC.
Conclusions: Our study suggests that plasma ghrelin levels are unlikely to have a causal relationship with overall, early-onset, and sex- and cancer subsite-stratified CRC risk.
Impact: This large-scale analysis adds to the growing body of evidence that plasma total ghrelin levels are not associated with CRC risk.
期刊介绍：
Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.
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