Raaj S Mehta1, Dawn Q Chong2, Mingyang Song3, Jeffrey A Meyerhardt4, Kimmie Ng4, Reiko Nishihara5, Zhirong Qian4, Teppei Morikawa4, Kana Wu6, Edward L Giovannucci7, Charles S Fuchs8, Shuji Ogino9, Andrew T Chan10. 1. Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts. 2. Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts; National Cancer Centre Singapore, Singapore. 3. Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 4. Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. 5. Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 6. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 7. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 8. Harvard Medical School, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. 9. Harvard Medical School, Boston, Massachusetts; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts. 10. Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts; Harvard Medical School, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts. Electronic address: achan@mgh.harvard.edu.
Abstract
BACKGROUND & AIMS: Patients with colorectal cancer (CRC) have high circulating levels of macrophage inhibitory cytokine-1 (MIC1 or growth differentiation factor 15), a marker of inflammation that might be involved in carcinogenesis. We analyzed blood samples collected from individuals before they were diagnosed with CRC to determine whether levels of MIC1 were associated with mortality. METHODS: We collected data on survival of 618 participants diagnosed with CRC who provided prediagnosis blood specimens in 1990 (Nurses' Health Study) and 1994 (Health Professionals' Follow-up Study) and were followed through 2010. Levels of MIC1 were measured by enzyme-linked immunosorbent assay and then were categorized into quartiles based on the known distribution of MIC1 levels among previously matched individuals without CRC (controls) within each cohort. We then examined the association of MIC1 levels with overall and CRC-specific mortality using Cox proportional hazards models, with adjustments for mortality-associated risk factors and other plasma markers of inflammation. We also assessed the relationship between levels of MIC1 and levels of prostaglandin-endoperoxide synthase 2 expression (PTGS2 or cyclooxygenase-2), measured in 245 tumor samples by immunohistochemistry. RESULTS: Compared with participants in the lowest quartile for plasma level of MIC1, the multivariate hazard ratio for CRC-specific death for participants in the highest quartile of MIC1 level was 2.40 (95% confidence interval: 1.33-4.34; P for linear trend = .009). The association of MIC1 with survival varied with level of PTGS2 expression in tumor samples (Pinteraction = .04). For individuals with PTGS2-positive tumors, the hazard ratio for CRC-specific death among those with high levels of MIC1 (equal to or greater than the median) was 2.13 (95% confidence interval: 0.99-4.58) compared with participants with low levels of MIC1 (below the median). In individuals with PTGS2-negative CRC, a high level of MIC1 was not associated with an increased risk of CRC-specific death (multivariate hazard ratio = 0.61; 95% confidence interval: 0.13-2.93). CONCLUSIONS: Based on an analysis of blood and colorectal tumor samples from 2 large studies, high plasma levels of MIC1 (growth differentiation factor 15) before diagnosis of CRC are associated with greater CRC-specific mortality, particularly in individuals with PTGS2-positive tumors.
BACKGROUND & AIMS:Patients with colorectal cancer (CRC) have high circulating levels of macrophage inhibitory cytokine-1 (MIC1 or growth differentiation factor 15), a marker of inflammation that might be involved in carcinogenesis. We analyzed blood samples collected from individuals before they were diagnosed with CRC to determine whether levels of MIC1 were associated with mortality. METHODS: We collected data on survival of 618 participants diagnosed with CRC who provided prediagnosis blood specimens in 1990 (Nurses' Health Study) and 1994 (Health Professionals' Follow-up Study) and were followed through 2010. Levels of MIC1 were measured by enzyme-linked immunosorbent assay and then were categorized into quartiles based on the known distribution of MIC1 levels among previously matched individuals without CRC (controls) within each cohort. We then examined the association of MIC1 levels with overall and CRC-specific mortality using Cox proportional hazards models, with adjustments for mortality-associated risk factors and other plasma markers of inflammation. We also assessed the relationship between levels of MIC1 and levels of prostaglandin-endoperoxide synthase 2 expression (PTGS2 or cyclooxygenase-2), measured in 245 tumor samples by immunohistochemistry. RESULTS: Compared with participants in the lowest quartile for plasma level of MIC1, the multivariate hazard ratio for CRC-specific death for participants in the highest quartile of MIC1 level was 2.40 (95% confidence interval: 1.33-4.34; P for linear trend = .009). The association of MIC1 with survival varied with level of PTGS2 expression in tumor samples (Pinteraction = .04). For individuals with PTGS2-positive tumors, the hazard ratio for CRC-specific death among those with high levels of MIC1 (equal to or greater than the median) was 2.13 (95% confidence interval: 0.99-4.58) compared with participants with low levels of MIC1 (below the median). In individuals with PTGS2-negative CRC, a high level of MIC1 was not associated with an increased risk of CRC-specific death (multivariate hazard ratio = 0.61; 95% confidence interval: 0.13-2.93). CONCLUSIONS: Based on an analysis of blood and colorectal tumor samples from 2 large studies, high plasma levels of MIC1 (growth differentiation factor 15) before diagnosis of CRC are associated with greater CRC-specific mortality, particularly in individuals with PTGS2-positive tumors.
Authors: Anne Cathrine Staff; Annika J Bock; Caroline Becker; Tibor Kempf; Kai C Wollert; Ben Davidson Journal: Gynecol Oncol Date: 2010-06-23 Impact factor: 5.482
Authors: Heiko Johnen; Shu Lin; Tamara Kuffner; David A Brown; Vicky Wang-Wei Tsai; Asne R Bauskin; Liyun Wu; Greg Pankhurst; Lele Jiang; Simon Junankar; Mark Hunter; W Douglas Fairlie; Nicola J Lee; Ronaldo F Enriquez; Paul A Baldock; Eva Corey; Fred S Apple; Maryann M Murakami; En-Ju Lin; Chuansong Wang; Matthew J During; Amanda Sainsbury; Herbert Herzog; Samuel N Breit Journal: Nat Med Date: 2007-11-04 Impact factor: 53.440
Authors: David A Brown; Fredrik Lindmark; Pär Stattin; Katarina Bälter; Hans-Olov Adami; Sigun L Zheng; Jianfeng Xu; William B Isaacs; Henrik Grönberg; Samuel N Breit; Fredrik E Wiklund Journal: Clin Cancer Res Date: 2009-10-20 Impact factor: 12.531
Authors: Sophie Shnaper; Isabelle Desbaillets; David A Brown; Anastasia Murat; Eugenia Migliavacca; Myriam Schluep; Sandrine Ostermann; Marie-France Hamou; Roger Stupp; Samuel N Breit; Nicolas de Tribolet; Monika E Hegi Journal: Int J Cancer Date: 2009-12-01 Impact factor: 7.396
Authors: Manol Jovani; Elizabeth E Liu; Samantha M Paniagua; Emily S Lau; Shawn X Li; Katherine S Takvorian; Bernard E Kreger; Greta Lee Splansky; Rudolf A de Boer; Amit D Joshi; Shih Jen Hwang; Chen Yao; Tianxiao Huan; Paul Courchesne; Martin G Larson; Daniel Levy; Andrew T Chan; Jennifer E Ho Journal: Cardiovasc Res Date: 2022-07-27 Impact factor: 13.081
Authors: Maša Alečković; Yong Wei; Gary LeRoy; Simone Sidoli; Daniel D Liu; Benjamin A Garcia; Yibin Kang Journal: Genes Dev Date: 2017-08-21 Impact factor: 11.361
Authors: Pooneh Mokarram; Mohammed Albokashy; Maryam Zarghooni; Mohammad Amin Moosavi; Zahra Sepehri; Qi Min Chen; Andrzej Hudecki; Aliyeh Sargazi; Javad Alizadeh; Adel Rezaei Moghadam; Mohammad Hashemi; Hesam Movassagh; Thomas Klonisch; Ali Akbar Owji; Marek J Łos; Saeid Ghavami Journal: Autophagy Date: 2017-02-23 Impact factor: 16.016