Principal Investigator

Andrew T
Awardee Organization

Massachusetts General Hospital
United States

Fiscal Year
Activity Code
Early Stage Investigator Grants (ESI)
Not Applicable
Project End Date

Precision Prevention Research Program

As an internationally recognized physician-investigator, I have dedicated my career to the prevention of colorectal cancer (CRC). My most substantial contributions have influenced the evidence base supporting aspirin’s effectiveness in reducing the risk of CRC and uncovered key molecular mechanisms underlying its anticancer activity. This work has helped advance the field to a first-if-its-kind milestone recommendation for population use of aspirin for cancer prevention by the US Preventive Services Task Force. However, growing data demonstrates that the effect of aspirin may differ according to host factors, including the gut microbiome and age, suggesting that a “one-size-fits-all” approach to aspirin chemoprevention is limited. Thus, developing novel approaches to prevention through molecular risk stratification is a high priority. Building on my expertise in molecular epidemiology, clinical trials, the gut microbiome, and clinical cancer prevention, my research vision is to develop a comprehensive Precision Prevention Research Program (PPRP) through this NCI Outstanding Investigator Award. The overarching goal of this PPRP is to leverage complementary sources of human data, including population-based studies, clinical cohorts, and “living biobanks” to study the entire continuum from healthy individuals to advanced cancer patients and with resolution from single cells to large populations to acquire a more complete, multifaceted view of how interventions can be tailored to prevent cancer. Our PPRP facilitates mechanistic discovery in population studies that can lead to rapid testing of novel, molecularly-inspired biomarkers in clinical cohorts, creating opportunity for “living biobanks” for rigorous validation and advanced mechanistic investigation. Moreover, this model is reciprocal. Our clinical cohorts and translational tools using patient-derived experimental systems may also identify novel mechanisms that can be examined within the context of our population studies to confirm their relevance to cancer and improve generalizability. Through this R35, I will develop and expand this PPRP through expansion of my work in aspirin chemoprevention. Aspirin is an exemplar agent to develop this platform since efficacy for CRC prevention has already been established and its association with adverse effects, such as bleeding, necessitate a tailored approach. As the Lancet Oncology Commission report concluded: “Perhaps the most promising precision-based approach to cancer prevention in the near future involves molecular selection for repurposed low-dose aspirin” and “in view of aspirin’s potential adverse effects (e.g., bleeding), tailoring aspirin use is a high priority”. By enhancing understanding of aspirin’s mode of action, this proposal may lead to novel mechanistic biomarkers or complementary preventative interventions that may maximize the benefits of aspirin while minimizing the harms. Over the long-term, I envision that this work will provide proof-of-concept for expansion of the PPRP program as a cost-efficient platform within which to move additional cancer preventive interventions rapidly into the clinic.


  • Mehta RS, Mayers JR, Zhang Y, Bhosle A, Glasser NR, Nguyen LH, Ma W, Bae S, Branck T, Song K, Sebastian L, Pacheco JA, Seo HS, Clish C, Dhe-Paganon S, Ananthakrishnan AN, Franzosa EA, Balskus EP, Chan AT, Huttenhower C. Gut microbial metabolism of 5-ASA diminishes its clinical efficacy in inflammatory bowel disease. Nature medicine. 2023 Mar;29(3):700-709. Epub 2023 Feb 23. PMID: 36823301
  • Wang K, Ma W, Wu K, Ogino S, Giovannucci EL, Chan AT, Song M. Long-Term Colorectal Cancer Incidence and Mortality After Colonoscopy Screening According to Individuals' Risk Profiles. Journal of the National Cancer Institute. 2021 Sep 4;113(9):1177-1185. PMID: 33734405
  • Joh HK, Lee DH, Hur J, Nimptsch K, Chang Y, Joung H, Zhang X, Rezende LFM, Lee JE, Ng K, Yuan C, Tabung FK, Meyerhardt JA, Chan AT, Pischon T, Song M, Fuchs CS, Willett WC, Cao Y, Ogino S, Giovannucci E, Wu K. Simple Sugar and Sugar-Sweetened Beverage Intake During Adolescence and Risk of Colorectal Cancer Precursors. Gastroenterology. 2021 Jul;161(1):128-142.e20. Epub 2021 Mar 19. PMID: 33753105
  • Zheng X, Hur J, Nguyen LH, Liu J, Song M, Wu K, Smith-Warner SA, Ogino S, Willett WC, Chan AT, Giovannucci E, Cao Y. Comprehensive Assessment of Diet Quality and Risk of Precursors of Early-Onset Colorectal Cancer. Journal of the National Cancer Institute. 2021 May 4;113(5):543-552. PMID: 33136160
  • Hur J, Otegbeye E, Joh HK, Nimptsch K, Ng K, Ogino S, Meyerhardt JA, Chan AT, Willett WC, Wu K, Giovannucci E, Cao Y. Sugar-sweetened beverage intake in adulthood and adolescence and risk of early-onset colorectal cancer among women. Gut. 2021 Dec;70(12):2330-2336. Epub 2021 May 6. PMID: 33958435
  • Kim MN, Lo CH, Corey KE, Liu PH, Ma W, Zhang X, Jovani M, Song M, Chan AT, Simon TG. Weight gain during early adulthood, trajectory of body shape and the risk of nonalcoholic fatty liver disease: A prospective cohort study among women. Metabolism: clinical and experimental. 2020 Dec;113:154398. Epub 2020 Oct 12. PMID: 33058854
  • Yuan C, Joh HK, Wang QL, Zhang Y, Smith-Warner SA, Wang M, Song M, Cao Y, Zhang X, Zoltick ES, Hur J, Chan AT, Meyerhardt JA, Ogino S, Ng K, Giovannucci EL, Wu K. Sugar-sweetened beverage and sugar consumption and colorectal cancer incidence and mortality according to anatomic subsite. The American journal of clinical nutrition. 2022 Jun 7;115(6):1481-1489. PMID: 35470384
  • Borozan I, Zaidi SH, Harrison TA, Phipps AI, Zheng J, Lee S, Trinh QM, Steinfelder RS, Adams J, Banbury BL, Berndt SI, Brezina S, Buchanan DD, Bullman S, Cao Y, Farris AB 3rd, Figueiredo JC, Giannakis M, Heisler LE, Hopper JL, Lin Y, Luo X, Nishihara R, Mardis ER, Papadopoulos N, Qu C, Reid EEG, Thibodeau SN, Harlid S, Um CY, Hsu L, Gsur A, Campbell PT, Gallinger S, Newcomb PA, Ogino S, Sun W, Hudson TJ, Ferretti V, Peters U. Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2022 Jan;31(1):210-220. Epub 2021 Nov 4. PMID: 34737207
  • Lo CH, Ni P, Yan Y, Ma W, Joshi AD, Nguyen LH, Mehta RS, Lochhead P, Song M, Curhan GC, Cao Y, Chan AT. Association of Proton Pump Inhibitor Use With All-Cause and Cause-Specific Mortality. Gastroenterology. 2022 Oct;163(4):852-861.e2. Epub 2022 Jul 1. PMID: 35788344
  • Cao Y, Nguyen LH, Tica S, Otegbeye E, Zong X, Roelstraete B, Chan AT, Warner BB, Stephansson O, Ludvigsson JF. Evaluation of Birth by Cesarean Delivery and Development of Early-Onset Colorectal Cancer. JAMA network open. 2023 Apr 3;6(4):e2310316. PMID: 37103933
  • Sikavi DR, Nguyen LH, Haruki K, Ugai T, Ma W, Wang DD, Thompson KN, Yan Y, Branck T, Wilkinson JE, Akimoto N, Zhong R, Lau MC, Mima K, Kosumi K, Morikawa T, Rimm EB, Garrett WS, Izard J, Cao Y, Song M, Huttenhower C, Ogino S, Chan AT. The Sulfur Microbial Diet and Risk of Colorectal Cancer by Molecular Subtypes and Intratumoral Microbial Species in Adult Men. Clinical and translational gastroenterology. 2021 Aug 1;12(8):e00338. PMID: 34333506
  • Nguyen LH, Cao Y, Hur J, Mehta RS, Sikavi DR, Wang Y, Ma W, Wu K, Song M, Giovannucci EL, Rimm EB, Willett WC, Garrett WS, Izard J, Huttenhower C, Chan AT. The Sulfur Microbial Diet Is Associated With Increased Risk of Early-Onset Colorectal Cancer Precursors. Gastroenterology. 2021 Nov;161(5):1423-1432.e4. Epub 2021 Jul 14. PMID: 34273347
  • Yang K, Prescott J, Hazra A, Meyerhardt JA, Zhang X, De Vivo I, Chan AT, Du M, Giovannucci EL, Nan H. Pre-diagnostic telomere length and colorectal cancer risk. Cancer epidemiology. 2022 Apr;77:102100. Epub 2022 Jan 13. PMID: 35033923
  • Kwon S, Ma W, Drew DA, Klempner SJ, Leonardo BM, Flynn JJ, Cao Y, Giovannucci EL, Bao Y, Fuchs CS, Song M, Chan AT. Association Between Aspirin Use and Gastric Adenocarcinoma: A Prospective Cohort Study. Cancer prevention research (Philadelphia, Pa.). 2022 Apr 1;15(4):265-272. PMID: 34980677
  • Wills C, He Y, Summers MG, Lin Y, Phipps AI, Watts K, Law PJ, Al-Tassan NA, Maughan TS, Kaplan R, Houlston RS, Peters U, Newcomb PA, Chan AT, Buchanan DD, Gallinger S, Marchand LL, Pai RK, Shi Q, Alberts SR, Gray V, West HD, Escott-Price V, Dunlop MG, Cheadle JP. A genome-wide search for determinants of survival in 1926 patients with advanced colorectal cancer with follow-up in over 22,000 patients. European journal of cancer (Oxford, England : 1990). 2021 Dec;159:247-258. Epub 2021 Nov 15. PMID: 34794066
  • Akimoto N, Väyrynen JP, Zhao M, Ugai T, Fujiyoshi K, Borowsky J, Zhong R, Haruki K, Arima K, Lau MC, Kishikawa J, Twombly TS, Takashima Y, Song M, Zhang X, Wu K, Chan AT, Meyerhardt JA, Giannakis M, Nowak JA, Ogino S. Desmoplastic Reaction, Immune Cell Response, and Prognosis in Colorectal Cancer. Frontiers in immunology. 2022 Mar 22;13:840198. doi: 10.3389/fimmu.2022.840198. eCollection 2022. PMID: 35392092
  • Wang Y, Cao Y, Lebwohl B, Song M, Sun Q, Green PHR, Giovannucci EL, Willett WC, Chan AT. Gluten Intake and Risk of Digestive System Cancers in 3 Large Prospective Cohort Studies. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2022 Sep;20(9):1986-1996.e11. Epub 2021 Nov 17. PMID: 34800737
  • Everett C, Li C, Wilkinson JE, Nguyen LH, McIver LJ, Ivey K, Izard J, Palacios N, Eliassen AH, Willett WC, Ascherio A, Sun Q, Tworoger SS, Chan AT, Garrett WS, Huttenhower C, Rimm EB, Song M. Overview of the Microbiome Among Nurses study (Micro-N) as an example of prospective characterization of the microbiome within cohort studies. Nature protocols. 2021 Jun;16(6):2724-2731. Epub 2021 Apr 21. PMID: 33883746
  • Merino J, Linenberg I, Bermingham KM, Ganesh S, Bakker E, Delahanty LM, Chan AT, Capdevila Pujol J, Wolf J, Al Khatib H, Franks PW, Spector TD, Ordovas JM, Berry SE, Valdes AM. Validity of continuous glucose monitoring for categorizing glycemic responses to diet: implications for use in personalized nutrition. The American journal of clinical nutrition. 2022 Jun 7;115(6):1569-1576. PMID: 35134821
  • Yang W, Sui J, Zhao L, Ma Y, Tabung FK, Simon TG, Lee DH, Zeng X, Nguyen LH, Meyerhardt JA, Chan AT, Giovannucci EL, Zhang X. Association of Inflammatory and Insulinemic Potential of Diet and Lifestyle with Risk of Hepatocellular Carcinoma. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Apr;30(4):789-796. Epub 2021 Jan 29. PMID: 33514605
  • Drew DA, Klempner SJ, Chan AT. Metabolomics as a Tool for Biomarker Discovery in Gastric Cancer. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Sep;30(9):1601-1603. PMID: 34475120
  • Devall MAM, Drew DA, Dampier CH, Plummer SJ, Eaton S, Bryant J, Díez-Obrero V, Mo J, Kedrin D, Zerjav DC, Takacsi-Nagy O, Jennelle LT, Ali MW, Yilmaz ÖH, Moreno V, Powell SM, Chan AT, Peters U, Casey G. Transcriptome-wide In Vitro Effects of Aspirin on Patient-derived Normal Colon Organoids. Cancer prevention research (Philadelphia, Pa.). 2021 Dec;14(12):1089-1100. Epub 2021 Aug 13. PMID: 34389629
  • Kim H, Lipsyc-Sharf M, Zong X, Wang X, Hur J, Song M, Wang M, Smith-Warner SA, Fuchs C, Ogino S, Wu K, Chan AT, Cao Y, Ng K, Giovannucci EL. Total Vitamin D Intake and Risks of Early-Onset Colorectal Cancer and Precursors. Gastroenterology. 2021 Oct;161(4):1208-1217.e9. Epub 2021 Jul 7. PMID: 34245763
  • Bakshi A, Cao Y, Orchard SG, Carr PR, Joshi AD, Manning AK, Buchanan DD, Umar A, Winship IM, Gibbs P, Zalcberg JR, Macrae F, McNeil JJ, Lacaze P, Chan AT. Aspirin and the Risk of Colorectal Cancer According to Genetic Susceptibility among Older Individuals. Cancer prevention research (Philadelphia, Pa.). 2022 Jul 5;15(7):447-454. PMID: 35348611
  • Hua X, Dai JY, Lindström S, Harrison TA, Lin Y, Alberts SR, Alwers E, Berndt SI, Brenner H, Buchanan DD, Campbell PT, Casey G, Chang-Claude J, Gallinger S, Giles GG, Goldberg RM, Gunter MJ, Hoffmeister M, Jenkins MA, Joshi AD, Ma W, Milne RL, Murphy N, Pai RK, Sakoda LC, Schoen RE, Shi Q, Slattery ML, Song M, White E, Marchand LL, Chan AT, Peters U, Newcomb PA. Genetically Predicted Circulating C-Reactive Protein Concentration and Colorectal Cancer Survival: A Mendelian Randomization Consortium Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Jul;30(7):1349-1358. Epub 2021 May 10. PMID: 33972368
  • Lyu Z, Hang D, He X, Wu K, Cao Y, Rosner B, Chan AT, Ogino S, Li N, Dai M, Giovannucci EL, Song M. Simple Prediction Model for Colorectal Serrated Polyps: Development and External Validation Study in U.S. Prospective Cohorts. Cancer prevention research (Philadelphia, Pa.). 2023 May 1;16(5):293-302. PMID: 36857746
  • Mahady SE, Margolis KL, Chan A, Polekhina G, Woods RL, Wolfe R, Nelson MR, Lockery JE, Wood EM, Reid C, Ernst ME, Murray A, Thao L, McNeil JJ. Major GI bleeding in older persons using aspirin: incidence and risk factors in the ASPREE randomised controlled trial. Gut. 2021 Apr;70(4):717-724. Epub 2020 Aug 3. PMID: 32747412
  • Hang D, Wang L, Fang Z, Du M, Wang K, He X, Khandpur N, Rossato SL, Wu K, Hu Z, Shen H, Ogino S, Chan AT, Giovannucci EL, Zhang FF, Song M. Ultra-processed food consumption and risk of colorectal cancer precursors: results from 3 prospective cohorts. Journal of the National Cancer Institute. 2023 Feb 8;115(2):155-164. PMID: 36477589
  • Mehta RS, Kochar BD, Kennelty K, Ernst ME, Chan AT. Emerging approaches to polypharmacy among older adults. Nature aging. 2021 Apr;1(4):347-356. Epub 2021 Mar 22. PMID: 37117591
  • Jachno KM, Heritier S, Woods RL, Mahady S, Chan A, Tonkin A, Murray A, McNeil JJ, Wolfe R. Examining evidence of time-dependent treatment effects: an illustration using regression methods. Trials. 2022 Oct 6;23(1):857. PMID: 36203169
  • Joshi AD, Chan AT. Racial Differences in Epigenetic Aging of the Colon: Implications for Colorectal Cancer. Journal of the National Cancer Institute. 2021 Nov 29;113(12):1618-1619. PMID: 33377963
  • Nguyen LH, Cao Y, Batyrbekova N, Roelstraete B, Ma W, Khalili H, Song M, Chan AT, Ludvigsson JF. Antibiotic Therapy and Risk of Early-Onset Colorectal Cancer: A National Case-Control Study. Clinical and translational gastroenterology. 2022 Jan 13;13(1):e00437. PMID: 35029165
  • Zoltick ES, Smith-Warner SA, Yuan C, Wang M, Fuchs CS, Meyerhardt JA, Chan AT, Ng K, Ogino S, Stampfer MJ, Giovannucci EL, Wu K. Sugar-sweetened beverage, artificially sweetened beverage and sugar intake and colorectal cancer survival. British journal of cancer. 2021 Sep;125(7):1016-1024. Epub 2021 Jul 15. PMID: 34267328
  • Brennan CA, Nakatsu G, Gallini Comeau CA, Drew DA, Glickman JN, Schoen RE, Chan AT, Garrett WS. Aspirin Modulation of the Colorectal Cancer-Associated Microbe Fusobacterium nucleatum. mBio. 2021 Apr 6;12. (2). PMID: 33824205
  • Polychronidis G, Wang K, Lo CH, Wang L, He M, Knudsen MD, Wu K, Joshi AD, Ogino S, Giovannucci EL, Chan AT, Song M. Gallstone Disease and Risk of Conventional Adenomas and Serrated Polyps: A Prospective Study. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Dec;30(12):2346-2349. Epub 2021 Oct 7. PMID: 34620626
  • Carreras-Torres R, Kim AE, Lin Y, Díez-Obrero V, Bien SA, Qu C, Wang J, Dimou N, Aglago EK, Albanes D, Arndt V, Baurley JW, Berndt SI, Bézieau S, Bishop DT, Bouras E, Brenner H, Budiarto A, Campbell PT, Casey G, Chan AT, Chang-Claude J, Chen X, Conti DV, Dampier CH, Devall MAM, Drew DA, Figueiredo JC, Gallinger S, Giles GG, Gruber SB, Gsur A, Gunter MJ, Harrison TA, Hidaka A, Hoffmeister M, Huyghe JR, Jenkins MA, Jordahl KM, Kawaguchi E, Keku TO, Kundaje A, Le Marchand L, Lewinger JP, Li L, Mahesworo B, Morrison JL, Murphy N, Nan H, Nassir R, Newcomb PA, Obón-Santacana M, Ogino S, Ose J, Pai RK, Palmer JR, Papadimitriou N, Pardamean B, Peoples AR, Pharoah PDP, Platz EA, Rennert G, Ruiz-Narvaez E, Sakoda LC, Scacheri PC, Schmit SL, Schoen RE, Shcherbina A, Slattery ML, Stern MC, Su YR, Tangen CM, Thomas DC, Tian Y, Tsilidis KK, Ulrich CM, van Duijnhoven FJB, Van Guelpen B, Visvanathan K, Vodicka P, Cenggoro TW, Weinstein SJ, White E, Wolk A, Woods MO, Hsu L, Peters U, Moreno V, Gauderman WJ. Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2023 Mar 6;32(3):315-328. PMID: 36576985
  • Merino J, Joshi AD, Nguyen LH, Leeming ER, Mazidi M, Drew DA, Gibson R, Graham MS, Lo CH, Capdevila J, Murray B, Hu C, Selvachandran S, Hammers A, Bhupathiraju SN, Sharma SV, Sudre C, Astley CM, Chavarro JE, Kwon S, Ma W, Menni C, Willett WC, Ourselin S, Steves CJ, Wolf J, Franks PW, Spector TD, Berry S, Chan AT. Diet quality and risk and severity of COVID-19: a prospective cohort study. Gut. 2021 Nov;70(11):2096-2104. Epub 2021 Sep 6. PMID: 34489306
  • Simon TG, Chan AT. Lifestyle and Environmental Approaches for the Primary Prevention of Hepatocellular Carcinoma. Clinics in liver disease. 2020 Nov;24(4):549-576. Epub 2020 Aug 25. PMID: 33012445
  • Li Y, Wang DD, Satija A, Ivey KL, Li J, Wilkinson JE, Li R, Baden M, Chan AT, Huttenhower C, Rimm EB, Hu FB, Sun Q. Plant-Based Diet Index and Metabolic Risk in Men: Exploring the Role of the Gut Microbiome. The Journal of nutrition. 2021 Sep 4;151(9):2780-2789. PMID: 34114015
  • Simon TG, Kim MN, Luo X, Liu X, Yang W, Ma Y, Chong DQ, Fuchs CS, Stampfer M, Giovannucci EL, Chan AT, Zhang X. Adiposity, Adulthood Weight Change, and Risk of Incident Hepatocellular Carcinoma. Cancer prevention research (Philadelphia, Pa.). 2021 Oct;14(10):945-954. Epub 2021 Jul 15. PMID: 34266856
  • Akimoto N, Zhao M, Ugai T, Zhong R, Lau MC, Fujiyoshi K, Kishikawa J, Haruki K, Arima K, Twombly TS, Zhang X, Giovannucci EL, Wu K, Song M, Chan AT, Cao Y, Meyerhardt JA, Ng K, Giannakis M, Väyrynen JP, Nowak JA, Ogino S. Tumor Long Interspersed Nucleotide Element-1 (LINE-1) Hypomethylation in Relation to Age of Colorectal Cancer Diagnosis and Prognosis. Cancers. 2021 Apr 22;13. (9). PMID: 33922024
  • Labadie JD, Hua X, Harrison TA, Banbury BL, Huyghe JR, Sun W, Shi Q, Yothers G, Alberts SR, Sinicrope FA, Goldberg RM, George TJ, Penney KL, Phipps AI, Cohen SA, Peters U, Chan AT, Newcomb PA. Genetic Predictors of Severe Skin Toxicity in Patients with Stage III Colon Cancer Treated with Cetuximab: NCCTG N0147 (Alliance). Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 2021 Feb;30(2):404-411. Epub 2020 Nov 17. PMID: 33203692
  • Yan MK, Orchard SG, Adler NR, Wolfe R, McLean C, Rodriguez LM, Woods RL, Gibbs P, Chan AT, Haydon A, Mar VJ. Effect of Aspirin on Melanoma Incidence in Older Persons: Extended Follow-up of a Large Randomized Double-blind Placebo-controlled Trial. Cancer prevention research (Philadelphia, Pa.). 2022 Jun 2;15(6):365-375. PMID: 35395069

Clinical Trials

Study Name Clinical Trial ID
ASPIRED-XT: ASPirin Intervention for the REDuction of Colorectal Cancer Risk -EXTension NCT05056896