Brian J. Reid

Appointments and Affiliations

Fred Hutchinson Cancer Research Center
Human Biology and Public Health Sciences Divisions
Full Member
University of Washington
Genome Sciences
Adjunct Professor
University of Washington
School of Medicine
Professor of Medicine
Professional Headshot of Brian Reid

Mailing Address

Fred Hutchinson Cancer Research Center
P.O. Box 19024
Seattle, Washington 98109-1024
United States



M.D., University of Washington, 1980
Ph.D., University of Washington, Genetics, 1975
B.S., University of Washington, Chemistry, 1969

Professional Experience

  • 1980-1981         Intern in Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  • 1981-1982         Assistant Resident Physician in Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  • 1982-1983         Senior Resident Physician in Medicine, Brigham and Women's Hospital, Boston, Massachusetts
  • 1982-1983         Chief Resident Physician in Primary Care, Brigham and Women's Hospital, Boston, Massachusetts
  • 1983-1985         Fellow in Gastroenterology, University of Washington, Seattle, Washington
  • 1985-1986         Acting Instructor in Medicine, University of Washington, Seattle, Washington
  • 1986-1988         Acting Assistant Professor in Medicine, University of Washington Seattle, Washington
  • 1988-1993         Assistant Professor in Medicine, University of Washington Seattle, Washington
  • 1993-1998         Associate Professor in Medicine, University of Washington, Seattle, Washington
  • 1995-1998         Adjunct Associate Professor of Genetics, University of Washington Seattle, Washington
  • 1996-                Full Member, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
  • 1998-                Professor of Medicine, University of Washington, Seattle, Washington
  • 1998-                Adjunct Professor of Genetics, University of Washington, Seattle, Washington
  • 1998-2002         Program Head in Gastrointestinal Oncology, Fred Hutchinson Cancer Research Center
  • 1999-                Full Member, Division of Human Biology, Fred Hutchinson Cancer Research Center 

Board Certification

American Board of Internal Medicine, 1984
American Board of Internal Medicine
Gastroenterology Subspecialty Board, 1990

Honors and Awards

Summa Cum Laude, 1969
Phi Beta Kappa
Phi Lambda Upsilon
Alpha Omega Alpha
Seattle Academy of Internal Medicine Award, 1980
R. Robert and Sally D. Funderburg Research Scholar Award, 1993

Research Interests

The Seattle Barrett’s Esophagus Study: Evolution and Cancer

Dr. Reid has been fortunate to lead this study since its inception in 1983. To our knowledge, this is the only study that was designed to investigate the temporal course of somatic genomic evolution from an epithelial precursor to cancer, and it has been at the innovative edge of evolution and cancer ever since. We are investigating evolutionary dynamics as the cause of “disease dynamics” responsible for over- and underdiagnosis of risk. The study has an experienced team of investigators representing the mix of scientific expertise required to study evolutionary dynamics in the dawn of the genomic age of cancer research. This expertise includes genetics, genomics, evolutionary biology, epidemiology, biostatistics, bioinformatics, computational biology, and clinical medicine. We are early adopters of rapidly advancing genome technologies, including high-density SNP arrays and whole genome sequencing, which allow us to study somatic genomic evolution in individuals with Barrett's esophagus who do and do not progress to esophageal adenocarcinoma over prolonged periods of time. Our investigators include Drs. Thomas L. Vaughan (FHCRC), Patricia L. Blount (FHCRC/UW), Xiaohong Li, (FHCRC), Thomas Paulson (FHCRC), Mary Kuhner (UW), Carlo C. Maley (UCSF) and Robert D. Odze (Harvard Medical School).

Disease Dynamics

“…it has become evident that the word “cancer” encompasses cellular abnormalities with widely variable natural courses: Some grow extremely rapidly, others do so more slowly, others stop growing completely, and some even regress. Clinicians are left with the realization that the word “cancer” is less a prediction about disease dynamics and more a pathological description made at a single point in time. Continued adherence to the dictionary definition of cancer, however, can lead to harm—including overuse of anticancer therapies.”
H. Gilbert Welch, William Black, JNCI 2010; 102:605

Evolutionary Dynamics

"Acquired genetic lability permits stepwise selection of variant sublines and underlies tumor progression."
Peter Nowell, Science 1976; 194:23

The Reid laboratory investigates the hypothesis that clonal evolutionary dynamics are the cause of “disease dynamics” that govern the different natural histories of “cancers” and “premalignant” conditions in which some individuals progress rapidly while others progress slowly or not at all.

About Brian J. Reid, MD, PhD

Brian Reid is the Founder and Director of the Seattle Barrett's Esophagus Study (the Seattle Study). As an undergraduate and graduate student in Genetics, he and Lee Hartwell discovered yeast cell cycle mutations which led to basic research that proposed the first genetic model of eukaryotic cell division. This model became the basis for Lee Hartwell's well deserved Nobel Prize in 2001. After graduate school, Dr. Reid entered medical school to study neoplastic evolution with the goal of improving care for patients who are at risk for or have cancer. He has been investigating Barrett's esophagus since 1983. The goal of Dr. Reid's work on Barrett's esophagus is to understand the mechanisms by which environmental exposures (i.e. aspirin or other nonsteroidal antiinflammatory agents) affect the evolution of clones that lead to the development of esophageal adenocarcinoma in patients with Barrett's esophagus. Recent research in the Seattle Study, and other studies around the world, indicate that attempts to reduce mortality of esophageal adenocarcinoma are limited by overdiagnosis of benign Barrett's that remains stable for the lifetime of an individual and underdiagnosis of life-threatening early esophageal adenocarcinoma. The Seattle Study is testing the hypothesis that these different disease dynamics are the result of clonal evolutionary dynamics that cause length bias. This understanding can then be used to develop interventions to prevent progression to cancer or to detect the cancers and premalignant abnormalities when they are early and curable, while avoiding invasive and costly interventions that cause significant adverse events in individuals who have little reason to expect benefit because their risk of cancer is low.

Basic Research

The discovery of yeast cell cycle mutants was a eureka moment. The discovery would allow detailed analysis of genes controlling the eukaryotic cell cycle where previously only G1, S, G2 and M were known. Early on, Lee, Joe Culotti, John Pringle and Brian developed an overarching model of the eukaryotic cell cycle and tested the hypotheses embedded within it daily, honing it over four years until it was published in Science. The lessons learned during this period have guided his subsequent cancer research: (1) select a research topic important enough to spend a career investigating; (2) team science, and (3) develop an overarching theory with rigorous testing and retesting of hypotheses to refine the overarching model. The Science paper was the basis for Lee’s well deserved Nobel Prize in 2001, and all the authors were invited to the Nobel Ceremony. The manuscript and the recognition of its scientific importance are highlights of their careers.

From PhD to MD

Two other members of the Department of Genetics, Drs. Stan Gartler and Phil Fialkow, taught Brian emerging concepts of clonal evolution in cancer, later articulated so eloquently by Dr. Peter Nowell in his 1976 Science classic. At the same time, Dr. John Cairns published a seminal manuscript proposing that intestinal tissue architecture was tumor suppressive. These were important overarching theories that could be tested rigorously through team science. They were especially important because understanding clonal evolution (Nowell, figure 1) and the homeostatic defenses against cancer could improve the lives of patients by preventing cancer or detecting it when it was early and curable. However, nothing in my PhD training had prepared me to study this process in humans so I decided to enter medical school. In medical school, I realized that the advent of fiberoptic endoscopy would allow visualization and biopsy of many conditions that predisposed to cancer, including Barrett’s esophagus. Dr. David Saunders, who taught the Gut course, arranged for me to study in Oxford with Dr. Sydney Truelove, a pioneer in inflammatory bowel disease research. He taught me to establish cohort studies to advance science and improve quality of care. I eventually selected Barrett's esophagus as a model of human neoplastic evolution.

Barrett’s esophagus

At the time, Barrett's esophagus and esophageal adenocarcinoma were thought to be rare conditions. However, the incidence and mortality of esophageal adenocarcinoma has been increasing more rapidly than any other cancer in western countries for the past four decades (figure). Esophageal adenocarcinoma is highly lethal with five year survival of less than 15%. Efforts in response to this near epidemic have reflected the prevailing clinical paradigm that Barrett’s esophagus arises as a complication of reflux and greatly predisposes to esophageal cancer. Thus, many have thought it evident that the route to reducing the mortality of esophageal adenocarcinoma is to screen patients in the population with reflux symptoms to identify individuals with Barrett’s, enroll them in long-term surveillance and aggressively treat them before they develop invasive cancer.

There’s only one problem with this strategy. It doesn’t work.

It doesn’t work because most individuals with Barrett’s (~95%) neither progress to nor die of esophageal cancer. Paradoxically, ~95% of patients who develop esophageal adenocarcinoma have no prior diagnosis of Barrett’s although the evidence suggests that it was present and undetected. Thus, Barrett’s and esophageal adenocarcinoma are extreme examples of dual challenges to reducing the mortality of many different cancers by prevention and early detection: overdiagnosis of a slowly or non-progressive condition that causes neither death nor symptoms during the lifetime of an individual, and underdiagnosis of life-threatening disease.

Over- and underdiagnosis are believed to be due to length bias (figure). From this perspective, the research challenges are (1) to determine the biological differences between rapidly progressive disease and slowly or non-progressive conditions and (2) the time window for early detection of rapidly progressive disease. The continued dramatic rise in the incidence and mortality of esophageal adenocarcinoma underscores the ineffectiveness of current approaches and the need for a fresh, evidence-based strategy.

Scientific Leadership

Dr. Reid has become increasingly concerned about two of the greatest challenges to reducing the morbidity and mortality of cancer: overdiagnosis of slowly progressing condistions that will cause neither symptoms nor death during the lifetime of an individual, and underdiagnosis of rapidly progressing life threatening early disease that later presents as an advanced malignancy with high mortality.

Our hypothesis is that overdiagnosis occurs when tissue defenses, such as those hypothesized by Cairns, predominate (Reid, et al, 2011; Reid, et al, 2010) and that cancer develops when these defenses are overcome, leading to genome-wide instability. For more than a decade Dr. Reid has participated in variety of think tanks, commissions, task forces, and working groups to promote cancer research and improve patient and population health. In 2005, he became a founding member of BEACON, an international consortium, serving on the steering committee and co-chairing the genetics committee for seven years. Two meetings in 2008, the Santa Fe Institute Workshop on “Integrating Evolutionary Theory into Cancer Biology” and a subsequent NCI meeting on Evolutionary Theory and Cancer combined with rapid advances in genomic technologies, which was accelerated by a 2004 NCI/NHGRI workshop on "sequencing cancer genomes," resulted in a marked increase in integrating evolutionary theory into cancer research although the actual number of investigators still remains underrepresented in cancer prevention and early detection research. The 2012 NCI DCP meeting on the natural history of occult neoplasms brought population, clinical, genomic, and evolutionary researchers together to focus on cancer disease dynamics that underlie over- and underdiagnosis of risk.

2001  NCI/NIDDK Barrett’s Esophagus Working Group 
2001-2003   NCI Stomach and Esophagus Progress Review Group; Co-chair
2003-2006 AACR Task Force on Cancer Prevention; Writing committee and Co-chair esophageal cancer
2004 NCI/NHGRI Workshop. "Sequencing Cancer Genomes"
2005-2007 NCI Translational Research Working Group; Co-chair organization and funding committee; Biomarker manuscript writing committee
2005 Barrett’s Esophagus Esophageal Adenocarcinoma Consortium (BEACON); Founding member
2005-2012 BEACON Steering committee, Co-chair genetics committee
2006-2007 National Commission on Digestive Diseases; Co-chair Esophageal Cancer
2007 NCI Barrett’s esophagus translational research working group; Co-chair
2008 Santa Fe Institute Workshop “Integrating Evolutionary Theory into Cancer Biology”
2008 NCI A New Look at Evolution and Evolutionary Theory in Cancer
2008 NCI The Coding, Decoding, Transfer, and Translation of Information in Cancer
2008 NCI/AACR Charting the Future of Cancer Prevention
2010 NCI Rethinking the Role of Infectious Agents in Cancer
2011 NCI Meeting on Gastric and Esophageal Cancers
2011 NCI Esophageal Cancer Disease Working Group in the Cancer Genome Atlas (TCGA)
2011-2012  NCI DCP Defining the Molecularly-Informed Natural History of Occult Neoplasms Meeting; Organizing Committee

Selected Peer Review Publications

Best | Most Relevant | Risk & Protective Factors | Recent



1. Hartwell, L.H., Culotti, J.C., Pringle, J.R. and Reid, B.J. Genetic control of the cell-division cycle in yeast: A model.  Science 183:46-51, 1974.
This was first genetic model of the eukaryotic cell cycle. This model became the basis for the 2001 Nobel Prize in Physiology or Medicine.

2. Blount, P.L., Meltzer, S.J., Yin, J., Huang, Y., Krasna, M.K. and Reid, B.J. Clonal ordering of 17p and 5q allelic losses in Barrett dysplasia and adenocarcinoma.   Proc. Nat. Acad. Sci. USA 90: 3221-3225, 1993.
This manuscript was the first to use spatial genetic dependency analysis (“clonal ordering”) to infer the order in which clonal genetic abnormalities developed during neoplastic evolution. Clonal ordering has subsequently been used in many other noeplastic conditions, and recently to construct phylogenetic trees based on somatic genomic alterations found in advanced cancers. (Gerlinger et al NEJM 2012; 366:883).

3. Barrett, M.T., Sanchez, C.A., Prevo, Laura J., Galipeau, P.C., Wong, D.J., Paulson, T.G., Rabinovitch, P.S. and Reid, B.J. Evolution of neoplastic cell lineages in Barrett’s esophagus.  Nature Genetics, 22: 106-109, 1999.
This was the first model of somatic genetic clonal evolution based on clonal ordering analyses over space and time in individuals at risk for cancer. This manuscript was recently cited in a study of copy number alterations, genome duplication and aneuploidy in multiple cancer types, including esophageal adenocarcinoma (Carter et al, Nature Biotechnology 30:413).

4. Maley, C.C., Galipeau, P.C., Finley, J.C., Wongsurawat, V.J., Li, X, Sanchez, C.A., Paulson, T.G., Blount, P.L., Rabinovitch, P.S. and Reid, B.J. Genetic clonal diversity predicts progression to esophageal adenocarcinoma, Nature Genet 38: 468-473, 2006.
This paper reported that clonal genetic diversity, a measure derived from evolutionary biology, was an independent risk factor for progression from Barrett’s esophagus to esophageal adenocarcinoma. This manuscript and number 9, below, were recently cited in a study of breast cancer that highlighted the importance of genetic diversity in intratumor heterogeneity to more effectively plan treatment strategies (Park et al J. Clin Invest 2010; 120:636).

5. Galipeau, P.C., Li, X., Blount, P.L., Maley, C.C., Sanchez, C.A., Odze, R.D., Ayub, K, Rabinovitch, P.S., Vaughan, T.L. and Reid, B.J. NSAIDs Modulate CDKN2A, TP53, and DNA Content Risk for Progression to Esophageal Adenocarcinoma. PLoS Medicine 4: 342-54, 2007.
This was a ten-year prospective cohort study in which we found that 9p LOH, 17p LOH and DNA content abnormalities, assessed by STR polymorphisms and DNA content flow cytometry, identified individuals with Barrett’s esophagus at high and low risk for progression to esophageal adenocarcinoma. We also demonstrated that risk could be modulated by environmental factors because current use of aspirin and other NSAIDs was associated with a markedly decreased rate of progression to esophageal adenocarcinoma in high risk individuals.

Most Relevant

6. Galipeau P.C., Cowan D.S., Sanchez C.A., Barrett M.T., Emond M.J., Levine D.S., Rabinovitch P.S., Reid B.J. 17p (p53) allelic losses, 4N (G2/tetraploid) populations, and progression to aneuploidy in Barrett’s esophagus. Proc Nat Acad Sci USA, 93: 7081-7084, 1996.
In this manuscript, we were the first to report that inactivation of TP53 in diploid cell populations was associated with genome duplication as evidenced by cell populations with increased 4N DNA content that preceded aneuploidization during prospective follow-up. This manuscript was recently cited in a large study of copy number alterations and genome duplications in many cancer types (Carter, et Nature Biotechnology 30: 413) as well as in review articles exploring relationships among genome duplication, aneuploidy and cancer (for example, Storchova and Pellman, Nature Reviews Molecular and Cell Biology 2004; 5:45 and Holland and Cleveland EMBO reports 2012; 13:501).

7. Mei, R., Galipeau, P.C., Prass, C., Berno, A. Ghandour, G., Patil, N., Wolff, R.K., Chee, M.S., Reid, B.J. and Lockhart, D.J. Genome-wide Detection of Allelic Imbalance Using Human SNPs and High Density DNA Arrays. Genome Research 10:1126-37, 2000.
This was the first manuscript to use genome-wide SNP arrays to assess loss of heterozygosity (LOH) in a human premalignant or malignant condition. It shows our long-term commitment to staying abreast of rapidly advancing genome technologies. This manuscript was recently cited in a comprehensive study of copy number alterations across multiple cancer types (Carter et al, Nature Biotechnology 30: 413).

8. Maley, C.C., Galipeau, P.C., Li, X., Sanchez, C.A., Paulson, T.G., Blount P.L. and Reid, B.J. The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Research. 64: 7629-33, 2004.
This manuscript reported that expansions of genetically unstable clones with TP53 or DNA content abnormalities were associated with an increased risk of evolving to esophageal adenocarcinoma.  Interestingly, the size of a clone with CDKN2A abnormalities was not an independent predictor of progression when TP53 status was considered.

9. Merlo, L.M.F., Pepper, J.W., Reid, B.J. and Maley, C.C. Cancer as an Evolutionary and Ecological Process. Nature Rev Cancer 6: 924-35, 2006.
This review summarized the literature on cancer as an evolutionary and ecological process for the cancer research community. It was recently cited in a New England Journal of Medicine article using clonal ordering and phylogenetic analysis of metastatic renal cell carcinomas (Gerlinger et al NEJM 2012; 366:883).

10. *Li, X., Galipeau, P.C., Sanchez, C.A., Blount, P.L., Maley, C.C., Arnaudo, J., Peiffer, D.A., Pokholok, D., Gunderson, K.L. and Reid, B.J. SNP-based Genome-wide Chromosome Copy Change, LOH, and Aneuploidy in Barrett’s Esophagus Neoplastic Progression. Cancer Prev Res 1: 413-423, 2008. NIHMS ID: 102648


Host and Environmental Risk and Protective Factors

Clonal evolution may be modulated by host and environmental factors, which can identify strategies for cancer prevention and early detection.

11. Vaughan TL, Dong LM, Blount PL, Ayub K, Odze RD, Sanchez CA, Rabinovitch PS, Reid BJ. Non-steroidal anti-inflammatory drugs and risk of neoplastic progression in Barrett's oesophagus: a prospective study. Lancet Oncol 6, 945-52, 2005.
This prospective cohort study reported that  current use of aspirin and other NSAIDs was associated with a decreased risk of progression from Barrett’s esophagus to esophageal adenocarcinoma as well as reduced progression to DNA content tetraploidy and aneuploidy.

12. Kantor ED, Onstad, L, Blount, PL, Reid, BJ, Vaughan, TL. Use of statin medications and risk of esophageal adenocarcinoma in persons with Barrett's esophagus. Cancer Epidemiol Biomarkers and Prevention 21, 456-61, 2012.
This prospective cohort study provided preliminary evidence that statin use may also have a protective association against progression from Barrett’s esophagus to esophageal adenocarcinoma.

13. Chao, D.L., Maley, C.C., Wu, X., Farrow, D.C., Galipeau, P.C., Sanchez, C.A., Paulson, T.G., Rabinovitch, P.S., Reid, B.J., Spitz, M.R. and Vaughan, T.L.  Mutagen sensitivity and neoplastic progression in patients with Barrett’s esophagus: A prospective analysis. Cancer Epidemiol Biomarkers and Prevention 15: 1935-40, 2006.
In this prospective study, we assessed sensitivity to bleomycin in peripheral blood lymphocytes in a cohort of 220 individuals with Barrett’s esophagus. Bleomycin-sensitive patients were at significantly greater risk of developing aneuploidy and nonsignificantly greater risk of cancer. Among patients with 17p LOH, including TP53 locus, increasing bleomycin sensitivity was associated with increased risk of progressing to esophageal adenocarcinoma (Ptrend < 0.001) and aneuploidy (Ptrend = 0.005).

14. Risques RA, Vaughan TL, Li X Odze RD, Blount PL, Ayub K, Gallaher JL, and Reid BJ, Rabinovitch PS. Leukocyte telomere length predicts cancer risk in patients with Barrett’s esophagus. Cancer Epidemiology Biomarkers & Prevention 16:2649-55, 2007.
In this prospective study, telomere length was measured by quantitative PCR in a cohort of 300 patients with Barrett's esophagus followed for a mean of 5.8 years. Shorter telomeres were associated with increased esophageal adenocarcinoma risk.

Recent Publications

Dai JY, de Tapsoba JD, Buas MF, Onstad LE, Levine DM, Risch HA, Chow W-H, Bernstein L, Ye W, Lagergren J et al..  2015.  A newly identified susceptibility locus near FOXP1 modifies the association of gastroesophageal reflux with Barrett's esophagus.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 24(11):1739-1747. Abstract
Hardikar S, Onstad L, Song X, Wilson AM, Montine TJ, Kratz M, Anderson GL, Blount PL, Reid BJ, White E et al..  2014.  Inflammation and oxidative stress markers and esophageal adenocarcinoma incidence in a Barrett's esophagus cohort.. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology. 23(11):2393-403. Abstract
Esserman LJ, Thompson IM, Reid BJ.  2014.  Changing the terminology of cancer--reply.. JAMA : the journal of the American Medical Association. 311(2):203.
Thrift AP, Risch HA, Onstad L, Shaheen NJ, Casson AG, Bernstein L, Corley DA, Levine DM, Chow W-H, Reid BJ et al..  2014.  Risk of Esophageal Adenocarcinoma Decreases with Height, Based on Consortium Analysis and Confirmed by Mendelian Randomization.. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. Abstract

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