FN590: Nutrition and Cancer                                                       

 

2 credits

 

Facilitators: Qing Jiang, Ph.D. and James C. Fleet, Ph.D.

 

Wednesday 3:30-5:20 pm       in Stone 232 or G53

 

 

Purpose: The risk for many forms of cancer is increased by environmental variables like poor diet.  Over the past 30 years, the molecular basis for several forms of cancer has been clarified; at the same time, population based trials have identified candidate nutrients that may regulate the risk of these same cancers.  The molecular basis for these diet/nutrient cancer relationships and the utility of these factors as both chemoprevention and chemotherapeutics is known for some of these agents.  The goal of this course is to give you an overview of the principles of cancer biology, to identify approaches to study the role of specific nutrients or bioactive compounds in molecular pathogenesis of cancer, and to discuss existing research on the influence of dietary factors on cancer disease risk.

 

Format:  This will be a discussion based course.  There will few formal lectures.  As such, you will need to read all assignments prior to attending class and you will need to come equipped with questions re: concepts, implications, methodology, and interpretation.  You must also be prepared to state your opinion on the subject being discussed.  If you do not understand the issue to be discussed due to lack of background in physiology, biochemistry, nutrition, or genetics, we expect that you will conduct additional research and reading in the area. 

 

Assignment: DUE APRIL 15, 2005

 

You will write a paper on a specific nutrient-cancer interaction. 

 

During this process, you will select TWO primary research papers for in-class discussion.  Provide me with a clean copy of each of these papers by MARCH 10, 2005.  I will select several of these papers for in class discussion. 

 

In the paper, we would like for you to:

·        Demonstrate that a relationship between the dietary factor and cancer exists

·        Demonstrate that there is a likely molecular basis for the relationship

·        Explain where the relationship is likely to influence cancer development

·        Explain prospects for using the dietary factor for the prevention or treatment of a specific cancer

·        Take a clear position regarding whether you believe the relationship is strong and reliable (and provide support for your position)

·        Identify gaps in our understanding that you believe need to be clarified in the future

 

We do not want you to convince us that your area has promise.  Rather we want you to critically evaluate the relationship that you choose.

 

Paper formatting:

·        15 pages (not including citations or a cover page)

·        double spaced

·        12 pt type

·        1 inch margins

·        > 10 primary research papers as citations

·        number each page and include your name at the top of each page

 

 

Grading

                                                                        Percent                       Points

Attendance                                           20%                             200

 

Class participation                                40%                             400

 

Paper                                                   40%                             400

 

 

 

Participation:

 

   Each student will be required to participate in discussions of class material and research articles.  While voluntary participation will be appreciated, we will call upon students for their answers/insights/opinions. Failure to actively participate will negatively influence your grade.  The following guidelines will help you understand the level of participation that is required for each grade level:

·        no participation =  no points

·        participation only when called upon

o       response demonstrating a lack of understanding of the material = 260 pts.

o       response provides only the minimum (correct) information = 300 pts

o       response provides insightful or thoughtful information = 340 pts

·        voluntary participation

o       response demonstrating a lack of understanding of the material = 260 pts.

o       response provides minimum (correct) information = 340 pts

o       response provided insightful or thoughtful information = 400 pts

 

 

Class Schedule:

Week of

 

PART I:  ESSENTIALS OF CANCER BIOLOGY AND  PATHOPHYSIOLOGY

 

Jan 12:         Class Business and Discussion on the Nature of Cancer

(Jiang and Fleet, Stone 232)

 

Required Reading:

Molecular Cell Biology 5th Edition Chapter 23

 

Futreal P. et al., (2004) A census of human cancer genes.  Nature Reviews: Cancer 4:177-183.

 

Jan 19:         Nature of Cancer cont’  (Fleet, Stone 232)

                        Molecular Pathophysiology of Colon and Prostate Cancer

 

Discussion questions: 

What is the relationship between clinical pathology and molecular pathology?

 

Required Readings:

Fearon, E.R. and Vogelstein, B. (1990) A genetic model for colorectal tumorigenesis.  Cell 61:759-767.

 

Arends, J.W. (2000) Molecular interactions in the Vogelstein model of colorectal carcinoma.  J. Pathol. 1990:412-416.

 

Kasper, S. (2004) Survey of genetically engineered mouse models for prostate cancer: Analyzing the molecular basis of prostate cancer development, progression, and metastasis.  J. Cell. Biochem. (on-line) http://www3.interscience.wiley.com/cgi-bin/fulltext/109800644/HTMLSTART

 

 

Jan 26:       Epigenetics and the Nature of Mutation (Jiang, Stone G-53)

                        Inflammation and Tumor Promotion

 

Required Readings:

 

Coussens, L.M. and Werb, Z. (2002) Inflammation and cancer.  Nature, 420, 860-867.

 

Egger, G., et al., (2004) Epigenetics in human disease and prospects for epigenetic therapy.  Nature, 429, 457-463.

 

 

Feb 2:           Nutrition and Cancer Overview (Jiang and Fleet, Stone G-53)

                       

Discussion Questions:

What are the differences between chemoprevention and chemotherapy and how does that influence our view of the relationship between dietary factors and cancer?

 

Required Reading:

Bingham, S., and Riboli, E. (2004) Diet and Cancer – The European prospective investigation into cancer and nutrition.  Nature Reviews: Cancer 4:206-215.

 

Nelson, P.S. and Montgomery, B. (2003) Unconventional therapy for prostate cancer: Good, Bad, or questionable?  Nature Reviews: Cancer 3:845-858.

 

 

 

Feb 9:           Beta carotene and lung cancer: Epidemiology (Fleet, Stone G53)

 

Discussion Questions:

What level of evidence is necessary to make a reliable link between a dietary factor and cancer prevention?  To justify an intervention trial? To influence public health and medical practice?

 

Required Reading:

 

The Alpha-Tocopherol, Beta Carotene Prevention Study Group (1994) The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers.  N. Engl. J. Med. 330:1029-1035.

 

Omenn GS et al. (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med. 1996 May 2;334(18):1150-5.

Hennekens, C.H. et al., (1996) Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease.  N. Engl. J. Med. 334:1145-1149.

 

Duffield-Lillico, A.J. and Begg, C.B. (2004) Reflections on the landmark studies of B-carotene supplementation.  J. Natl. Cancer. Inst. 96:1729-31.

 

 

Feb 16:         Beta carotene and lung cancer: Molecular actions (Fleet, Stone 232)

 

Required Reading:

Liu C. et al., (2000) Effects of physiological versus pharmacological b-carotene supplementation on cell proliferation and histopathological changes in the lungs of cigarette smoke-exposed ferrets.  Carcinogenesis 21:2245-2253.

 

Liu C. et al., (2004) Low dose b-carotene supplementation of ferrets attenuates smoke-induced lung phosphorylation of JNK, p38 MAPK, and p53 proteins.  J. Nutr. 2705-2710.

 

Tibaduiza, E.C. et al. (2002) Excentric cleavage products of b-carotene inhibit estrogen receptor positive and negative breast tumor cell growth in vitro and inhibit activator protein-1 mediated transcriptional activation.  J. Nutr. 132:1368-1375. (Focus

 

Benkoussa M. et al., (2002) Retinoic acid receptor inhibit AP1 activation by regulating extracellular signal-regulated kinase and CBP recruitment to an AP-1-responsive promoter.  Mol. Cell. Biol. 22:4522-4532.

 

Feb 23:         Vitamin D and prostate cancer: Epidemiology (Fleet, Stone G53)

 

Required Reading:

Hanchette, C.L. and Schwartz, G.G. (1992) Geographic patterns of prostate cancer mortality. Evidence for a protective effect of ultraviolet radiation.  Cancer 70:2861-2869.

 

Ahonen, M.H. et al., (2000) Prostate cancer risk and prediagnostic serum 25-hydroxyvitamin D levels (Finland). Cancer Causes and Control 11:847-852.

 

Tuohimaa, P. et al., (2004) Both high and low levels of blood vitamin D are associated with a higher prostate cancer risk: a longitudinal, nested case-control study in the Nordic countries.  Int. J. Cancer 108:104-108. (Following the references are two letters to the editor and the replies from the authors).

 

Mar 2:          Vitamin D and prostate cancer: Molecular actions (Fleet, Stone G53)

 

Required Reading:

Crescioli, C. et al., (2003) Inhibition of spontaneous and androgen-induced prostate growth by a nonhypercalcemic calcitriol analog. Endocrinology 144:3046-3057.

 

Whitlatch, L.W. et al., (2002) 25-hydroxyvitamin D-1a-hydroxylase activity is diminished in human prostate cancer cells and is enhanced by gene transfer.  J. Steroid Biochem. Mol. Biol. 81:135-140.

 

Barclay, W.W. et al., (2005) Vitamin D receptor and p21 mediate the antiproliferative action of 1,25-dihydroxyvitamin D3 in mouse prostatic epithelial cells. In review.

 

 

 

Mar 9:          Vitamin E and cancer: epidemiology and molecular actions (Jiang, Stone G53)

 

Required Reading:

 

Chan, J.M., et al., (1999) Supplemental Vitamin E intake and prostate cancer risk in a large cohort of men in the United States.  Cancer Epidemilogy, Biomarkers and Prevention. 8, 893-899.

 

Helzlsouer, K. J., et al., (2000) Association between alpha-tocopherol, gamma-tocopherol, selenium, and subsequent prostate cancer.  J. Natl. Cancer Inst., 92, 2018-2023.

 

Gysin, R., et al., (2002) Gamma-tocopherol inhibits human cancer cell cycle progression and cell proliferation by down-regulation of cyclins.  FASEB J., 16, 1592-4.

 

Jiang, Q., et al., (2004) Gamma-tocopherol or combinations of vitamin E forms induce cell death in human prostate cancer cells by interrupting sphingolipid synthesis.  Proc. Natl. Acad. Sci. USA, 101, 17835-17830.

 

 

Mar 16:        NO CLASS - SPRING BREAK

 

Mar 23:        Phytochemicals and cancer: Green Tea (Jiang, Stone G53)

 

Required Reading:

 

Gupta, S., et al., (2001) Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols.  Proc. Natl. Acad. Sci. USA, 98, 10350-10355.

 

Fang, M. Z., et al., (2003) Tea polyphenol (-)-epigallocatechin-3-gallate inhibits DNA methyltransferase and reactivates methylation-silenced genes in cancer cell lines.  Cancer Res., 63, 7563-7570.

 

Pisters, K. M. W., et al., (2001) Phase I trial of oral green tea extract in adult patients with solid tumors.  J. Clin. Oncology, 19, 1830-1838.

 

 

PART IV: STUDENT SELECTED PAPERS

 

(We will discuss whether the topic is to be limited to OBESITY/ENERGY METABOLISM OR FOLATE AND CANCER at the first class meeting)

 

Mar 30:        Student Selected papers (Stone G-53)         

 

Required Reading:

 

April 6:         NO CLASS - Experimental Biology Meeting

 

Required Reading:

 

April 13:      Student Selected papers (Stone 232)

 

Required Reading:

 

April 20:      Student Selected papers (Stone G-53)

 

Required Reading:

 

April 27:      Student Selected papers (Stone G-53)

 

Required Reading:

Readings:

Cancer Related Web sites:

 

National Cancer Institute -  http://cancer.gov/

 

Cancer Genome Anatomy Project (cgap) - http://cgap.nci.nih.gov/

 

International Cancer Research Portfolio - http://www.cancerportfolio.org/