Liang Wang1, Chun-Han Lo2, Xiaosheng He3, Dong Hang4, Molin Wang5, Kana Wu6, Andrew T Chan7, Shuji Ogino8, Edward L Giovannucci9, Mingyang Song10. 1. Center of Gastrointestinal Surgery, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 2. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 3. Department of Colorectal Surgery, the Six Affiliated Hospital, Sun Yat-sen University, Guangzhou, P.R. China. 4. Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, P.R. China. 5. Department of Epidemiology, Harvard T.H. Chan School of Public Health, 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. Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 8. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard, Cambridge, Massachusetts; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 9. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts. 10. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: mingyangsong@mail.harvard.edu.
Abstract
BACKGROUND & AIMS: The molecular features of colorectal tumors differ with their anatomic location. Colorectal tumors are usually classified as proximal or distal. We collected data from 3 cohorts to identify demographic, clinical, anthropometric, lifestyle, and dietary risk factors for colorectal cancer (CRC) at 7 anatomic subsites. We examined whether the associations differ among refined subsites and whether there are trends in associations from cecum to rectum. METHODS: We collected data from the Nurses' Health Study, Nurses' Health Study 2, and Health Professionals Follow-up Study (45,351 men and 178,016 women, followed for a median 23 years) on 24 risk factors in relation to risk of cancer in cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid junction, and rectum. Hazard ratios were estimated using Cox proportional hazards regression. We tested for linear and nonlinear trends in associations with CRC among subsites and within proximal colon, distal colon, and rectum. RESULTS: We documented 3058 cases of CRC (474 in cecum, 633 in ascending colon, 250 in transverse colon, 221 in descending colon, 750 in sigmoid colon, 202 in rectosigmoid junction, and 528 in rectum). The positive associations with cancer risk decreased, from cecum to rectum, for age and family history of CRC. In contrast, the inverse associations with cancer risk increased, from cecum to rectum, for endoscopic screening and intake of whole grains, cereal fiber, and processed red meat. There was a significant nonlinear trend in the association between CRC and female sex, with hazard ratios ranging from 1.73 for ascending colon cancer to 0.54 for sigmoid colon cancer. For proximal colon cancers, the association with alcohol consumption and smoking before age 30 years increased from the cecum to transverse colon. For distal colon cancers, the positive association with waist circumference in men was greater for descending vs sigmoid colon cancer. CONCLUSIONS: In an analysis of 3058 cases of CRC, we found that risk factor profiles differed for cancers along the colorectum. Proximal vs distal classifications are not sufficient to encompass the regional variations in colorectal tumor features and risk factors.
BACKGROUND & AIMS: The molecular features of colorectal tumors differ with their anatomic location. Colorectal tumors are usually classified as proximal or distal. We collected data from 3 cohorts to identify demographic, clinical, anthropometric, lifestyle, and dietary risk factors for colorectal cancer (CRC) at 7 anatomic subsites. We examined whether the associations differ among refined subsites and whether there are trends in associations from cecum to rectum. METHODS: We collected data from the Nurses' Health Study, Nurses' Health Study 2, and Health Professionals Follow-up Study (45,351 men and 178,016 women, followed for a median 23 years) on 24 risk factors in relation to risk of cancer in cecum, ascending colon, transverse colon, descending colon, sigmoid colon, rectosigmoid junction, and rectum. Hazard ratios were estimated using Cox proportional hazards regression. We tested for linear and nonlinear trends in associations with CRC among subsites and within proximal colon, distal colon, and rectum. RESULTS: We documented 3058 cases of CRC (474 in cecum, 633 in ascending colon, 250 in transverse colon, 221 in descending colon, 750 in sigmoid colon, 202 in rectosigmoid junction, and 528 in rectum). The positive associations with cancer risk decreased, from cecum to rectum, for age and family history of CRC. In contrast, the inverse associations with cancer risk increased, from cecum to rectum, for endoscopic screening and intake of whole grains, cereal fiber, and processed red meat. There was a significant nonlinear trend in the association between CRC and female sex, with hazard ratios ranging from 1.73 for ascending colon cancer to 0.54 for sigmoid colon cancer. For proximal colon cancers, the association with alcohol consumption and smoking before age 30 years increased from the cecum to transverse colon. For distal colon cancers, the positive association with waist circumference in men was greater for descending vs sigmoid colon cancer. CONCLUSIONS: In an analysis of 3058 cases of CRC, we found that risk factor profiles differed for cancers along the colorectum. Proximal vs distal classifications are not sufficient to encompass the regional variations in colorectal tumor features and risk factors.
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