Spotlight On...

Over the past three decades, our scientific understanding of colorectal cancer has grown exponentially, shedding light onto a once obscure and highly lethal disease. Much of that illumination has come from a singular source: the tireless, innovative work of Dr. John D. Potter.

Potter received his medical degree in 1971 and his PhD in 1984, both from the University of Queensland in Australia. He worked at CSIRO Division of Human Nutrition, Adelaide, Australia (1977-86), with a short period at the University of Adelaide during that time span. Subsequently, he was on the faculty of the University of Minnesota’s School of Public Health for eight years (1986-94) before joining the Fred Hutchinson Cancer Research Center and the University of Washington in 1994.

From 2002 to 2007, Potter was Senior Vice-President and Director of the Hutchinson Center's Division of Public Health Sciences, the largest cancer etiology and prevention research program in any cancer center in the world.

Potter has been involved in the study of colorectal cancer and its premalignant precursors (polyps) since the late 1970s, when he undertook the first ever population-based case-control study of this cancer. Potter and colleagues have subsequently contributed steadily to what we know about the role of a variety of dietary and other factors that increase risk of colorectal cancer, including protein, meat, sugar, alcohol, smoking, and obesity, as well as those that reduce risk, such as vegetables and their constituents, vitamin E, folate, calcium, physical activity, and aspirin.

In collaboration with colleagues at Fred Hutchinson Cancer Research Center (FHCRC) and Dr Marty Slattery at the University of Utah, Potter has also focused on the way in which the risks associated with such specific exposures might be modified by inherited metabolic variability. They have shown that inherited genetic variation in body chemistry modifies the extent to which some exposures that increase risk (e.g., meat and smoking) and some that decrease risk (e.g., folate - a B vitamin found especially in green leafy vegetables) modify risks somewhat differently, depending on underlying genetic makeup.

Pharmaceutical preventive agents, such as aspirin, are also subject to metabolic processes: Potter and colleagues have shown that, although aspirin generally lowers the risk of colorectal cancer and polyps of the colon, some individuals are not protected because of the way in which they metabolize and excrete this drug. They continue to work on the nature of metabolism of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin and have shown that genetically determined variations in the pro-inflammatory processes that are the target of aspirin are themselves also associated with variations in risk of colorectal cancer.

Potter, Slattery, and colleagues have also shown in a series of studies that smoking is a major risk factor for one kind of premalignant precursor lesion in the colon (hyperplastic polyps and, probably, the related serrated adenomas), but not for another kind (adenomatous polyps) and, in parallel, for a particular subset of colon cancers and not other kinds. More generally, this adds weight to a growing body of evidence that different kinds of human cancers in the same organ result from specific causes in the environment and in people’s behavior: that is, there are specific and predictable variations in the patterns of environmental factors that increase the risk of particular biologic subtypes of colon cancer - a pattern that is also true for breast cancer.

With Tony McMichael, Potter first proposed that female hormones would protect against colon cancer, an hypothesis that he has subsequently tested in a variety of ways, showing a reduced risk of colon cancer and polyps associated with aspects of reproductive history and with both early high-dose oral contraceptives and with post-menopausal hormones. With Slattery, he has also shown that obesity (a source of estrogens in post-menopausal women) is associated with an elevated risk of colon cancer in men but largely not in women.

A collaboration with Dr. Polly Newcomb at FHCRC, and other colleagues across the U.S. and internationally, has resulted in the colorectal Cancer Familial Registry – the world’s largest collection of families with histories of colorectal cancer. In addition to studying environment and genes in colorectal cancer, Potter has also focused on the role of plant foods in lowering risk of cancer and on studies aimed at understanding risk and intermediate biology in breast, pancreas, colorectal, and childhood cancer, at developing usable biomarkers for screening and early detection, and at monitoring cancer progression in high-risk individuals.

Dr. Potter remains conscious of the need to facilitate interdisciplinary cross-talk. He has published on the need for a proper understanding of study design, and he believes that the disciplines must learn each others' languages and cultures to work together to provide the best opportunities for undertaking multidisciplinary research.

Between 1993 and 1997, Dr. Potter chaired an international panel that produced Food, Nutrition, and the Prevention of Cancer: A Global Perspective, a seminal report on the feasibility of reducing cancer incidence through diet and other environmental factors. Along with Dr. Daehee Kang of the Seoul National University in Korea, Dr. Potter leads the Asia Cohort Consortium. This project is planned to involve over 1 million participants across Asia. He is also Senior Advisor to, and Chair of, the Governing Committee of the Tomorrow Project, a cohort study that will involve about 300,000 people across Canada. The findings of both of these cohort studies will help generate new ways to prevent cancer and reduce cancer risks for all.

Potter - the author or co-author of over 500 scientific papers, chapters and books - is the recipient of numerous awards, including the American Association for Cancer Research's DeWitt Goodman Lectureship for international leadership in research in nutrition, cancer, and cancer prevention, India’s Gopalan Oration Gold Medal for outstanding contributions in the field of nutrition science and the 2009 AACR-American Cancer Society Award for Research Excellence in Cancer Epidemiology and Prevention.

Potter has been a member of the NCI Board of Scientific Counselors and Board of Scientific Advisors and of the Board of Directors of the American Association for Cancer Research. He is currently Member and Senior Advisor,FHCRC, and Professor of Epidemiology, University of Washington School of Public Health & Community Medicine, both in Seattle, Washington. He also has recently held a visiting appointment at the Cambridge Research Institute, Cambridge, UK.

HIGHLIGHTED PAPERS

1. McMichael AJ, Potter JD: Reproduction, endogenous and exogenous sex hormones and colon cancer: a review and hypothesis. J Nat Cancer Inst 65:1201-7, 1980
2. Ross JR, Potter JD, Robison LR. Infant Leukemia, topoisomerase II inhibitors, and the MLL gene. J Natl Cancer Inst 86:1678-80, 1994
3. Potter JD, Cerhan JR, Sellers TA, McGovern PG, Drinkard C, Kushi LR, Folsom AR. Progesterone and estrogen receptors and mammary neoplasia in the Iowa Women’s Health Study: How many kinds of breast cancer are there? Cancer Epidemiol Biomarkers Prev 4:319-26, 1995
4. World Cancer Research Fund Panel (Potter JD, Chair) Food, Nutrition and the Prevention of Cancer: A Global Perspective Washington, D.C.: American Institute for Cancer Research, 1997
5. Potter JD. Colorectal cancer: molecules and populations. J Nat Cancer Inst 91:916-32, 1999
6. Lampe J, King IB, Li S, Grate MT, Barale KV, Chen C, Feng Z, Potter JD. Brassica vegetables increase and apiaceous vegetables decrease cytochrome P450 1A2 activity in humans: changes in caffeine metabolite ratios in response to controlled vegetable diets. Carcinogenesis 21:1157-62, 2000
7. Potter JD. At the interfaces of epidemiology, genetics, and genomics. Nature Reviews Genetics 2:142-7, 2001
8. O'Sullivan JN, Bronner MP, Brentnall TA, Finley JC, Shen W, Emerson S, Emond MJ, Gollahon KA, Moskovitz AH, Crispin DA, Potter JD, Rabinovitch PS. Chromosomal instability in ulcerative colitis is related to telomere shortening. Nat Genet 32:280-4, 2002
9. Morimoto LM, Newcomb PA, Ulrich CM, Bostick RM, Lais CJ, Potter JD. Risk Factors for Hyperplastic and Adenomatous Polyps: Evidence for Malignant Potential? Cancer Epidemiol Biomarkers Prev 11:1012-8, 2002
10. Fleming MA, Potter JD, Ramirez CJ, Ostrander GK, Ostrander EA. Understanding missense mutations in the BRCA1 gene: An evolutionary approach. Proc. Natl. Acad. Sci 100:1151-6, 2003
11. Newcomb PA, Storer BE, Morimoto LM, Templeton A, Potter JD. Long-term efficacy of sigmoidoscopy in the reduction of colorectal cancer incidence. J Natl Cancer Inst 95:622-5, 2003
12. Potter JD. Epidemiology informing clinical practice: from bills of mortality to population laboratories. Nature Clin Pract Oncol 2:625-34, 2005
13. Potter JD. Morphogens, morphostats, microarchitecture and malignancy. Nature Reviews Cancer 7:464-74, 2007
14. Ulrich CM, Potter JD. Folate and Cancer—timing is everything. JAMA 297:2408-9, 2007
15. Potter JD, Lindor NM (eds.): Genetics of Colorectal Cancer New York, Springer, 2009.