Green Tea and Cancer Alison Chiang EPI295 October 30,2009
Overview Pathways to cancer Green tea Chemical composition Potential mechanisms General study findings Study 1 Study 2
How does cancer develop? http://www.abcam.com/ps/pdf/neuroscience/a4_cancer_card.pdf
Mutation Transformation Decreased Apoptosis Increased Proliferation Angiogenesis Intravasation Extravasation Metastases
Contributing Factors Inflammation Radiation Oxidation Smoking BMI Diet Cancer Infection
Protective Factors?
Green Tea Tea is the 2 nd most common drink worldwide Green tea accounts for 20% of tea consumption Green tea leaves are exposed to high temperatures to deactivate fermenting enzymes 1989: IARC claimed, There is inadequate evidence for the carcinogenicity in humans and experimental animals of tea drinking.
Polyphenols, catechins, and flavonoids oh my! Polyphenols Flavonoids Catechins Bigelow RLH and Cardelli JA. The green tea catechins, (-)-Epigallocatechin-3-gallate (EGCG) and (-)-Epicatechin-3-gallate (ECG), inhibit HGF/Met signaling in immortalized and tumorigenic breast epithelial cells. Oncogene, 2006. 25: 1922-1930. Theaflavins
Proposed Mechanisms Lambert JD et al. Inhibition of carcinogenesis by polyphenols: evidence from laboratory investigations. AJCN, 2005. 81(1):284S-291S.
Proposed Mechanisms Prevention of mutagenicity and genotoxicity Inhibition of biochemical markers for tumor initiation and promotion Induction of detoxification enzymes Trapping of active metabolites of carcinogens Antioxidant and free-radical scavenging activity so, does green tea actually help protect against cancer? It depends
Green Tea and Lung Cancer: Study One
Dietary Flavonoid Intake and Lung Cancer: A Population-based Case-control Study Yan Cui, MD, PhD 1, Hal Morgenstern, PhD 2, Sander Greenland, DrPH 3,4, Donald P. Tashkin, MD 5, Jenny T. Mao, MD 5, Lin Cai, MD, PhD 6, Wendy Cozen, DO, MPH 7, Thomas M. Mack, MD, MPH 7, Qing- Yi Lu, PhD 8, Zuo-Feng Zhang, MD, PhD 3 1 Office of Health Assessment and Epidemiology, Los Angeles County Department of Public Health, Los Angeles, California. 2 Department of Epidemiology, University of Michigan, Ann Arbor, Michigan. 3 Department of Epidemiology, University of California at Los Angeles, California. 4 Department of Statistics, University of California at Los Angeles, California. 5 Division of Pulmonary and Critical Care Medicine, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California. 6 Department of Epidemiology, School of Public Health, Fujian Medical University, Fujian, China. 7 Department of Preventive Medicine, Keck School of Medicine at University of Southern California, Los Angeles, California. 8 Center for Human Nutrition, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, California.
Methodology Population-based case-control study in Los Angeles County from 1999 to 2004 Exclusion criteria: No food frequency data Caloric intake <500 or >4500 per day Age exclusions Total: 558 lung cancer cases and 837 controls Semiquantitative questionnaire based on Brief Block FFQ
Methodology (cont d) To calculate OR: Unconditional logistic regression analysis Adjustments for: Age Sex Race/ethnicity Years of schooling Smoking status Pack-years of tobacco smoking Daily energy intake
Results Odds ratios show inverse associations between epicatechin, catechin, quercetin, and kaempferol with lung cancer among smokers. Non-smokers showed no significant association. Total flavonoid intake was not significantly associated with lung cancer
Discussion Catechins Antimutagenic Inhibit lung tumorigenesis by tobacco-specific carcinogens Quercetin In vitro inhibition of lung tumorigenesis Several epi studies also confirm findings Kaempferol Potent ROS scavenger Inhibits cell growth enzymes and induces apoptosis in lung cancer cells
Green Tea and Lung Cancer: Study Two
Green tea, black tea consumption and risk of lung cancer: A meta-analysis Naping Tang a, Yuemin Wu b, Bo Zhou c, Bin Wang c, Rongbin Yu d a National Shanghai Center for New Drug Safety Evaluation and Research, Shanghai Institute of Pharmaceutical Industry, 199 Guoshoujing Road, Zhangjiang Hi-Tech Park, Pudong, Shanghai 201203, China, b Department of General, Surgery, People s Hospital of Liyang City, Liyang, Jiangsu Province, China, c Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu Province, China, d Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu Province, China
Methodology Criteria for inclusion: Published between 1966 and November 2008 Prospective or case-control Exposure of interest was tea consumption Unrelated subjects Risk estimates with 95% CIs were reported 12 studies on green tea and four additional studies on both green and black tea intake
Methodology (cont d) To calculate summary RR: Random effects model To analyze dose-response: Method proposed by Greenland and Longnecker and Orsini et al. Took logarhythm of RR and estimated slope across categories of tea consumption (used midpoint of upper and lower boundaries for the category as the reported dose) To measure heterogeneity: Q and I 2 statistics
Borderline significant inverse association between highest green tea consumption and lung cancer. 0.74, (0.58 0.94)
No statistically significant reduction in lung cancer risk associated with black tea consumption.
Statistically significant association between increasing green tea consumption by 2 cups/day and a decreased risk of developing lung cancer
No statistically significant association between increasing black tea consumption by 2 cups/day and risk of developing lung cancer
Discussion Green tea may be beneficial whereas black tea may not be. Dose-response? Issues with heterogeneity? Statistically significant Attributed to study design Prospective studies had better RR than case-control
Green Tea and Lung Cancer: Future?
Limitations of current studies Self-reported data Tendency to over-report consumption of fruits and vegetables for dietary intake of flavonoids Difficulty in assessing tea consumption Cup size and preparation may vary considerably Duration of tea drinking Limited generalizability Populations studied so far have been localized
Suggestions for future study Expand study to populations outside of Europe, US, China, and Japan Large randomized trials Standardized consumption THANK YOU! Questions or comments?
References Ahmad N and Mukhtar H. Green Tea Polyphenols and Cancer: Biologic Mechanisms and Practical Implications. Nutrition Reviews, 1999. 57, 3:78-83. Cui Y et al. Dietary Flavonoid Intake and Lung Cancer A Population-based Case-control Study. Cancer, 2008. 112:2241 2248. Tang N et al. Green tea, black tea consumption and risk of lung cancer: A meta-analysis. Lung Cancer, 2009. 65: 275-283. Yang CS and Wang ZY. Tea and Cancer. JNCI, 1993. 85, 13:1038-1049.