Sabrina E Wang, Vivian Viallon, Matthew Lee, Niki Dimou, Fergus Hamilton, Carine Biessy, Tracy O'Mara, Maria Kyrgiou, Emma J Crosbie, Therese Truong, Gianluca Severi, Rudolf Kaaks, Renée Turzanski Fortner, Matthias B Schulze, Benedetta Bendinelli, Sieri Sabina, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Marta Crous-Bou, Maria-Jose Sánchez, Amaia Aizpurua, Daniel Rodriguez Palacios, Marcela Guevara, Ruth C Travis, Konstantinos K Tsilidis, Alicia Heath, James Yarmolinsky, Sabina Rinaldi, Marc J Gunter, Laure Dossus
{"title":"循环炎症和免疫反应蛋白与子宫内膜癌风险：巢式病例对照研究和孟德尔随机分析。","authors":"Sabrina E Wang, Vivian Viallon, Matthew Lee, Niki Dimou, Fergus Hamilton, Carine Biessy, Tracy O'Mara, Maria Kyrgiou, Emma J Crosbie, Therese Truong, Gianluca Severi, Rudolf Kaaks, Renée Turzanski Fortner, Matthias B Schulze, Benedetta Bendinelli, Sieri Sabina, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Marta Crous-Bou, Maria-Jose Sánchez, Amaia Aizpurua, Daniel Rodriguez Palacios, Marcela Guevara, Ruth C Travis, Konstantinos K Tsilidis, Alicia Heath, James Yarmolinsky, Sabina Rinaldi, Marc J Gunter, Laure Dossus","doi":"10.1016/j.ebiom.2024.105341","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls).</p><p><strong>Findings: </strong>In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03-1.57)], HGF [1.48 (1.06-2.07)], PIK3AP1 [1.22 (1.00-1.50)] and CLEC4G [1.52 (1.00-2.32)] were positively associated; HSD11B1 [0.67 (0.49-0.91)], SCF [0.68 (0.49-0.94)], and CCL25 [0.80 (0.65-0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. In complementary MR analysis, IL-6 [OR per inverse-rank normalized NPX = 1.19 (95% CI 1.04-1.36)] and HSD11B1 [0.91 (0.84-0.99)] were associated with endometrial cancer risk.</p><p><strong>Interpretation: </strong>Altered IL-6 signalling and reduced glucocorticoid activity via HSD11B1 might play important roles in endometrial carcinogenesis.</p><p><strong>Funding: </strong>Funding for IIG_FULL_2021_008 was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme; Funding for INCA_15849 was obtained from Institut National du Cancer (INCa).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"108 ","pages":"105341"},"PeriodicalIF":9.7000,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11418138/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses.\",\"authors\":\"Sabrina E Wang, Vivian Viallon, Matthew Lee, Niki Dimou, Fergus Hamilton, Carine Biessy, Tracy O'Mara, Maria Kyrgiou, Emma J Crosbie, Therese Truong, Gianluca Severi, Rudolf Kaaks, Renée Turzanski Fortner, Matthias B Schulze, Benedetta Bendinelli, Sieri Sabina, Rosario Tumino, Carlotta Sacerdote, Salvatore Panico, Marta Crous-Bou, Maria-Jose Sánchez, Amaia Aizpurua, Daniel Rodriguez Palacios, Marcela Guevara, Ruth C Travis, Konstantinos K Tsilidis, Alicia Heath, James Yarmolinsky, Sabina Rinaldi, Marc J Gunter, Laure Dossus\",\"doi\":\"10.1016/j.ebiom.2024.105341\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls).</p><p><strong>Findings: </strong>In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03-1.57)], HGF [1.48 (1.06-2.07)], PIK3AP1 [1.22 (1.00-1.50)] and CLEC4G [1.52 (1.00-2.32)] were positively associated; HSD11B1 [0.67 (0.49-0.91)], SCF [0.68 (0.49-0.94)], and CCL25 [0.80 (0.65-0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. 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Circulating inflammatory and immune response proteins and endometrial cancer risk: a nested case-control study and Mendelian randomization analyses.
Background: Inflammation and immune dysregulation are hypothesized contributors to endometrial carcinogenesis; however, the precise underlying mechanisms remain unclear.
Methods: We measured pre-diagnostically 152 plasma protein biomarkers in 624 endometrial cancer case-control pairs nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Odds ratios (ORs) were estimated using conditional logistic regression, accounting for confounding and multiple comparisons. Proteins considered as associated with endometrial cancer risk were further tested in a two-sample Mendelian randomization (MR) analysis using summary data from the UK Biobank (n = 52,363) and the Endometrial Cancer Association Consortium (12,270 cases and 46,126 controls).
Findings: In the EPIC nested case-control study, IL-6 [OR per NPX (doubling of concentration) = 1.28 (95% confidence interval (CI) 1.03-1.57)], HGF [1.48 (1.06-2.07)], PIK3AP1 [1.22 (1.00-1.50)] and CLEC4G [1.52 (1.00-2.32)] were positively associated; HSD11B1 [0.67 (0.49-0.91)], SCF [0.68 (0.49-0.94)], and CCL25 [0.80 (0.65-0.99)] were inversely associated with endometrial cancer risk; all estimates had multiple comparisons adjusted P-value > 0.05. In complementary MR analysis, IL-6 [OR per inverse-rank normalized NPX = 1.19 (95% CI 1.04-1.36)] and HSD11B1 [0.91 (0.84-0.99)] were associated with endometrial cancer risk.
Interpretation: Altered IL-6 signalling and reduced glucocorticoid activity via HSD11B1 might play important roles in endometrial carcinogenesis.
Funding: Funding for IIG_FULL_2021_008 was obtained from Wereld Kanker Onderzoek Fonds (WKOF), as part of the World Cancer Research Fund International grant programme; Funding for INCA_15849 was obtained from Institut National du Cancer (INCa).
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍：
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.
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