Plasma Inflammatory Markers and Risk of Advanced Colorectal Adenoma in Women.
Evidence remains inconclusive about the association of systemic inflammatory markers with colorectal neoplasia. We investigated whether circulating inflammatory markers were associated with risk of advanced colorectal adenoma. We measured plasma macrophage inhibitory cytokine-1 (MIC-1), C-reactive protein (CRP), interleukin-6 (IL6), and soluble TNF receptor 2 (sTNFR-2) in blood samples drawn from 32,826 women in 1989 to 1990 in the Nurses' Health Study. Through 2008, we documented 757 cases of advanced colorectal adenomas (≥1 cm or any size with advanced histology); each case was matched by age and time of blood draw with one control randomly selected from participants who underwent lower endoscopy and did not have neoplasia. Plasma MIC-1 was associated with higher risk of advanced adenoma (Ptrend = 0.04), with an OR of 1.55 (95% confidence interval, 1.03-2.32) comparing extreme quintiles of MIC-1 after adjusting for colorectal cancer-risk factors and other inflammatory markers. Among cases, MIC-1 level was positively associated with the number of adenomas (P < 0.001) and gradually increased from adenomas located in the rectum, distal colon, and up to the proximal colon. There was a strong positive association between MIC-1 and risk of adenomas with multiplicity, ≥1 cm size and location in the proximal colon (all Ptrend < 0.05). CRP, IL6, or sTNFR-2 was not associated with adenoma risk. In conclusion, plasma MIC-1 was associated with higher risk of colorectal adenoma, especially multiple, large, and proximal adenomas. Our results provide further support for a role for MIC-1 in carcinogenesis and the potential for MIC-1 as an adjunctive biomarker for detection of advanced colorectal adenoma.
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Division of Gastroenterology, 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.
Mingyang
M
Song
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts.
Raaj S
RS
Mehta
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Kana
K
Wu
Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Boston, Massachusetts. Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.
Charles S
CS
Fuchs
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 and Harvard Medical School, Boston, Massachusetts.
Shuji
S
Ogino
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, Harvard Medical School, Boston, Massachusetts.
Edward L
EL
Giovannucci
Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts. Channing Division of Network Medicine, Department of Medicine, Harvard Medical School, Boston, Massachusetts. achan@partners.org.
Andrew T
AT
Chan
D000236:Adenoma / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D011446:Prospective Studies; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000097:blood; D012307:Risk Factors
D014408:Biomarkers, Tumor; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C508600:IL6 protein, human; D015850:Interleukin-6; D047889:Receptors, Tumor Necrosis Factor, Type II; D002097:C-Reactive Protein