We are affiliated with the Channing Laboratory, Epidemiology Section at Brigham and Women’s Hospital as well as the Harvard School of Public Health. Through this affiliation, we actively participate in research using the Harvard epidemiological cohort studies, including the Nurses’ Health Study I, Nurses’ Health Study II, and Health Professionals Follow-up Study. These cohorts provide unprecedented access to a range of longitudinally collected epidemiologic questionnaire data that are consistently updated over greater than 30 years of follow-up. Within these cohorts, we have archived biospecimens of plasma, DNA, and tumor material for correlative science and translational research projects.
Ashwin Ananthakrishnan, MD, MPH
Edward Huang, MD, MPH
Hamed Khalili, MD
1. Epidemiology of colorectal adenoma and cancer. Our specific focus is on the prevention of colorectal adenoma and cancer using chemopreventative drugs and lifestyle interventions. Most recently, aspirin has emerged as promising agent for prevention of colorectal cancer. We have been conducting studies evaluating the optimal dose and duration of aspirin therapy, as well as defining potential populations that may preferentially benefit. We are also interested in genetic and biochemical markers that may be used to stratify risk of colorectal cancer for individuals, as well as predict responsiveness to various interventions. This work is also being extended into using epidemiological methods to understand the role of inflammation in colorectal cancer risk and prognosis.
2. Genetic epidemiology of colorectal cancer. We coordinate the Harvard cohorts in a national consortium of epidemiological studies of colorectal cancer which have assembled to conduct a large scale genome wide association study of colorectal cancer. A principal aim of the consortium is to investigate the interaction between known environmental risk factors for colorectal cancer and genetic risk loci.
3. Epidemiology of gastrointestinal bleeding. Our specific focus is on lifestyle risk factors for gastrointestinal bleeding, including intake of medications such as aspirin and NSAIDs. We are also examining the influence of genetic and biomarker risk factors for gastrointestinal bleeding.
4. Molecular imaging of colorectal neoplasia. In collaboration with biotechnology firms, we are working to clinically translate novel near infrared activatable agents that selectively target tumor-specific cathepsin proteases. We are interested in using these agents with fluorescent imaging endoscopy to enhance the detection of colorectal neoplasia.5. Epidemiology of inflammatory bowel disease. Our specific focus is on lifestyle and dietary factors and risk of incident Crohn’s Disease and ulcerative colitis. Based on this work, we will ultimately examine how these factors interact with known genetic risk loci for Crohn’s and ulcerative colitis.
Selected Peer-reviewed Publications
1. Chan AT, Manson JE, Feskanich D, Stampfer MJ, Colditz GA, Fuchs CS. Long-term aspirin use and mortality in women. Arch Intern Med. 2007;167(6):562-72.
2. Chan AT, Ogino S, Fuchs CS. Aspirin and the risk of colorectal cancer in relation to the expression of COX-2. N Engl J Med. 2007;356(21):2131-42.
3. Cho E, Willett WC, Colditz GA, Fuchs CS, Wu K, Chan AT, Zeisel SH, Giovannucci EL. Dietary choline and betaine and the risk of distal colorectal adenoma in women. J Natl Cancer Inst. 2007;99(16):1224-31. PMCID: PMC2441932.
4. Feskanich D, Bain C, Chan AT, Pandeya N, Speizer FE, Colditz GA. Aspirin and lung cancer risk in a cohort study of women: dosage, duration and latency. Br J Cancer. 2007;97(9):1295-9.
5. Chan AT, Giovannucci EL, Meyerhardt JA, Schernhammer ES, Wu K, Fuchs CS. Aspirin dose and duration of use and risk of colorectal cancer in men. Gastroenterology. 2008;134(1):21-8. NIHMSID: NIHMS38884.
6. Kawasaki T, Nosho K, Ohnishi M, Suemoto Y, Glickman JN, Chan AT, Kirkner GJ, Mino-Kenudson M, Fuchs CS, Ogino S. Cyclooxygenase-2 overexpression is common in serrated and non-serrated colorectal adenoma, but uncommon in hyperplastic polyp and sessile serrated polyp/adenoma. BMC Cancer. 2008;8:33. PMCID: PMC2257954.
7. Berndt SI, Potter JD, Hazra A, Yeager M, Thomas G, Makar KW, Welch R, Cross AJ, Huang WY, Schoen RE, Giovannucci E, Chan AT, Chanock SJ, Peters U, Hunter DJ, Hayes RB. Pooled analysis of genetic variation at chromosome 8q24 and colorectal neoplasia risk. Hum Mol Genet. 2008;17(17):2665-2672. PMCID: PMC2561994.
8. Hazra A, Fuchs CS, Chan AT, Giovannucci EL, Hunter DJ. Association of the TCF7L2 polymorphism with colorectal cancer and adenoma risk. Cancer Causes Control. 2008;19(9):975-980. NIHMSID: NIHMS124556.
9. Nosho K, Kawasaki T, Chan AT, Ohnishi M, Suemoto Y, Kirkner GJ, Fuchs CS, Ogino S. Cyclin D1 is frequently overexpressed in microsatellite unstable colorectal cancer, independent of CpG island methylator phenotype. Histopathology. 2008;53(5):588-98. NIHMSID: NIHMS121770.
10. Ogino S, Nosho K, Kirkner GJ, Kawasaki T, Chan AT, Schernhammer ES, Giovannucci EL, Fuchs CS. A Cohort Study of Tumoral LINE-1 Hypomethylation and Prognosis in Colon Cancer. J Natl Cancer Inst. 2008;100(23):1734-8. PMCID: PMC2639290.
11. Ogino S, Kirkner GJ, Nosho K, Irahara N, Kure S, Shima K, Hazra A, Chan AT, Dehari R, Giovannucci EL, Fuchs CS. Cyclooxygenase-2 expression is an independent predictor of poor prognosis in colon cancer. Clin Cancer Res. 2008;14(24):8221-7. PMCID: PMC2679582.
12. Wolpin BM, Meyerhardt JA, Chan AT, Ng K, Chan JA, Wu K, Pollak MN, Giovannucci EL, Fuchs CS. Insulin, the Insulin-Like Growth Factor Axis, and Mortality in Patients With Nonmetastatic Colorectal Cancer. J Clin Oncol. 2009;27(2):165-7. PMCID: PMC2645084.
13. Chan AT, Zauber AG, Hsu M, Breazna A, Hunter DJ, Rosenstein RB, Eagle CJ, Hawk ET, Bertagnolli MM. Cytochrome P450 2C9 Variants Influence Response to Celecoxib for Prevention of Colorectal Adenoma. Gastroenterology. 2009;136(7):2127-36. PMCID: PMC2693443.
14. Wolpin BM, Chan AT, Hartge P, Chanock SJ, Kraft P, Hunter DJ, Giovannucci EL, Fuchs CS. ABO Blood Group and the Risk of Pancreatic Cancer. J Natl Cancer Inst. 2009;101(6):424-31. PMCID: PMC2657095.
15. Ogino S, Nosho K, Kirkner GJ, Shima K, Irahara N, Kure S, Chan AT, Engelman JA, Kraft P, Cantley LC, Giovannucci EL, Fuchs CS. PIK3CA Mutation Is Associated With Poor Prognosis Among Patients With Curatively Resected Colon Cancer. J Clin Oncol. 2009;27(9):1477-84. PMCID: PMC2659340.
16. Jacobson BC, Chan AT, Giovannucci EL, Fuchs CS. Body Mass Index and Barrett's Oesophagus in Women. Gut. 2009;58(11):1460-6. PMCID: PMC2763036.
17. Ogino S, Nosho K, Baba Y, Kure S, Shima K, Irahara N, Toyoda S, Chen L, Kirkner GJ, Wolpin BM, Chan AT, Giovannucci EL, Fuchs CS. A cohort study of STMN1 expression in colorectal cancer: body mass index and prognosis. Am J Gastroenterol. 2009;104(8):2047-56. PMCID: PMC2866652.
18. Chan AT, Ogino S, Fuchs CS. Aspirin use and survival after diagnosis of colorectal cancer. JAMA. 2009;302(6):649-58. PMCID: PMC2848289.
19. Meyerhardt JA, Ogino S, Kirkner GJ, Chan AT, Wolpin B, Ng K, Nosho K, Shima K, Giovannucci EL, Loda M, Fuchs CS. Interaction of molecular markers and physical activity on mortality in patients with colon cancer. Clin Cancer Res. 2009;15(18):5931-6. PMCID: PMC2745516.
20. Ng K, Wolpin BM, Meyerhardt JA, Wu K, Chan AT, Hollis BW, Giovannucci EL, Stampfer MJ, Willett WC, Fuchs CS. Prospective study of predictors of vitamin D status and survival in patients with colorectal cancer. Br J Cancer. 2009;101(6):916-23. PMCID: PMC2743349.
21. Ogino S, Nosho K, Meyerhardt JA, Kirkner GJ, Chan AT, Kawasaki T, Giovannucci EL, Loda M, Fuchs CS. Cohort Study of Fatty Acid Synthase Expression and Patient Survival in Colon Cancer. J Clin Oncol. 2009;26(35):5713-20. PMCID: PMC2630484.
22. Meyerhardt JA, Giovannucci EL, Ogino S, Kirkner GJ, Chan AT, Willett W, Fuchs CS. Physical activity and male colorectal cancer survival. Arch Intern Med. 2009;169(22):2102-8. PMCID: PMC2852183.
23. Baba Y, Nosho K, Shima K, Goessling W, Chan AT, Ng K, Chan JA, Giovannucci EL, Fuchs CS, Ogino S. PTGER2 overexpression in colorectal cancer is associated with microsatellite instability, independent of CpG island methylator phenotype. Cancer Epidemiol Biomarkers Prev. 2010. 19(3): 822-31. PMCID: PMC2837535.
24. Das KK, Nishino HT, Chan AT. Treatment-associated acute myeloid leukemia in a patient with Crohn's disease on 6-mercaptopurine. Inflamm Bowel Dis. 2010.
25. Baba Y, Nosho K, Shima K, Irahara N, Chan AT, Meyerhardt JA, Chung DC, Giovannucci EL, Fuchs CS, Ogino S. HIF1A overexpression is associated with poor prognosis in a cohort of 731 colorectal cancers. Am J Path. 2010. 176(5): 2292-2301. PMCID: PMC2861094.
26. Chan AT and Giovannucci EL. Primary Prevention of Colorectal Cancer. Gastroenterology. 2010. 138(6): 2029-2043. PMCID: Pending.
27. Chan AT. COX-2 Expression in Adenoma: An Imperfect Marker. Gut. 2010. 59(5): 622-9. PMCID: Pending.