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

CancerDiet

Smoking

Radiation

Inflammation

Oxidation

BMI

Infection

Contributing Factors

Protective Factors

?

Green Tea• Tea is the 2nd 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

TheaflavinsBigelow 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.

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, PhD1, Hal Morgenstern, PhD2, Sander Greenland, DrPH3,4, Donald P. Tashkin, MD5, Jenny T. Mao, MD5, Lin Cai, MD,

PhD6, Wendy Cozen, DO, MPH7, Thomas M. Mack, MD, MPH7, Qing-Yi Lu, PhD8, Zuo-Feng Zhang, MD, PhD3

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 Tanga, Yuemin Wub, Bo Zhouc, Bin Wangc, Rongbin Yud

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 I2 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.