Week 11 - Nutrients Genes and Cancer

Nutrients, Genes and Cancer Milly Ryan-Harshman, PhD, RD Cancer Themes: Online Lecture Articles Excessive energy intake Dietary fat Fruits and vegetables Dietary fibre Alcohol and caffeine Vitamin and mineral supplements Individual responsiveness Polymorphisms Feast or famine Nutritional genomics Improve research quality Identify at-risk populations Broaden cancer prevention strategies Green Tea Polyphenols & Cancer Prevention Camellia sinensis plant Three types of tea Black tea Green tea Oolong tea Green Tea Polyphenols & Cancer Prevention The methods of harvesting and processing of the tea leaves determines the type of tea and the kind of flavonoids present. Flavanol content varies little between three types, but catechins are affected by processing, so black tea contains theaflavins and thearubigens. Green Tea Polyphenols & Cancer Prevention Major catechins in green tea Epigallocatechin-3-gallate (EGCG) Epicatechin (EC) Epicatechin-3-gallate (ECG) Epigallocatechin (EGC) Green Tea & Cancer Epidemiology Improved prognosis of patients with breast cancer Green tea protection appears to function, in part, by reducing hormone levels associated with the risk of developing breast cancer Green tea reduces risk of cancers of the digestive tract Green Tea & Cancer Epidemiology Risk reduction for ovarian and prostate cancer Reduced risk of lung cancer in non-smokers, but no effect in smokers (women) However, there have been mixed results which may be due to either different flavonol content in different brands or to the rapid biotransformation and elimination of tea catechins after ingestion Green Tea & Cancer Epidemiology Catechol-O-methyltransferase, COMT, allele codes for an enzyme with higher activity Individuals who possess at least one copy of the low activity COMT allele experience greater risk reduction with green tea consumption (even black tea provides some benefit) Mechanisms of Green Tea Action The major receptor for EGCG (67LR) is found on many tumour cells and its expression correlated with invasion and metastasis Treatment with EGCG slowed growth of tumour cells EGCG treatment of breast cancer cells leads to a down regulation of the 67LR protein Mechanisms of Green Tea Action Green tea polyphenols have been shown to affect several key regulators of cell cycle progression (a process of division allowing the duplication of cells) http://mitworld.mit.edu/video/390/ Click to edit Master title style Click to edit Master subtitle style * * * Nutrients, Genes and Cancer Milly Ryan-Harshman, PhD, RD Cancer Themes: Online Lecture Articles Excessive energy intake Dietary fat Fruits and vegetables Dietary fibre Alcohol and caffeine Vitamin and mineral supplements Individual responsiveness Polymorphisms Feast or famine Nutritional genomics Improve research quality Identify at-risk populations Broaden cancer prevention strategies Green Tea Polyphenols & Cancer Prevention Camellia sinensis plant Three types of tea Black tea Green tea Oolong tea Green Tea Polyphenols & Cancer Prevention The methods of harvesting and processing of the tea leaves determines the type of tea and the kind of flavonoids present. Flavonol content varies little between three types, but catechins are affected by processing, so black tea contains theaflavins and thearubigens. Green Tea Polyphenols & Cancer Prevention Major catechins in green tea Epigallocatechin-3-gallate (EGCG) Epicatechin (EC) Epicatechin-3-gallate (ECG) Epigallocatechin (EGC) Green Tea & Cancer Epidemiology Improved prognosis of patients with breast cancer Green tea protection appears to function, in part, by reducing hormone levels associated with the risk of developing breast cancer Green tea reduces risk of cancers of the digestive tract Green Tea & Cancer Epidemiology Risk reduction for ovarian and prostate cancer Reduced risk of lung cancer in non-smokers, but no effect in smokers (women) However, there have been mixed results which may be due to either different flavonol content in different brands or to the rapid biotransformation and elimination of tea catechins after ingestion Green Tea & Cancer Epidemiology Catechol-O-methyltransferase, COMT, allele codes for an enzyme with higher activity Individuals who possess at least one copy of the low activity COMT allele experience greater risk reduction with green tea consumption (even black tea provides some benefit) Mechanisms of Green Tea Action The major receptor for EGCG (67LR) is found on many tumour cells and its expression correlated with invasion and metastasis Treatment with EGCG slowed growth of tumour cells EGCG treatment of breast cancer cells leads to a down regulation of the 67LR protein Mechanisms of Green Tea Action Green tea polyphenols have been shown to affect several key regulators of cell cycle progression (a process of division allowing the duplication of cells; cancer is a “disease” of cell cycle progression) Green tea polyphenols combat virtually all aspects of tumour cell physiology (growth, proliferation, survival, lifespan and angiogenesis) http://mitworld.mit.edu/video/390/ Clinical Studies with Green Tea Oral green tea extracts equivalent to 7-8 cups of Japanese green tea three times daily shown to be safe, so clinical trials with extracts are underway Nutrients, Genes and Cancer Milly Ryan-Harshman, PhD, RD Cancer Themes: Online Lecture Articles Excessive energy intake Dietary fat Fruits and vegetables Dietary fibre Alcohol and caffeine Vitamin and mineral supplements Individual responsiveness Polymorphisms Feast or famine Nutritional genomics Improve research quality Identify at-risk populations Broaden cancer prevention strategies Green Tea Polyphenols & Cancer Prevention Camellia sinensis plant Three types of tea Black tea Green tea Oolong tea Green Tea Polyphenols & Cancer Prevention The methods of harvesting and processing of the tea leaves determines the type of tea and the kind of flavonoids present. Flavonol content varies little between three types, but catechins are affected by processing, so black tea contains theaflavins and thearubigens. Green Tea Polyphenols & Cancer Prevention Major catechins in green tea Epigallocatechin-3-gallate (EGCG) Epicatechin (EC) Epicatechin-3-gallate (ECG) Epigallocatechin (EGC) Green Tea & Cancer Epidemiology Improved prognosis of patients with breast cancer Green tea protection appears to function, in part, by reducing hormone levels associated with the risk of developing breast cancer Green tea reduces risk of cancers of the digestive tract Green Tea & Cancer Epidemiology Risk reduction for ovarian and prostate cancer Reduced risk of lung cancer in non-smokers, but no effect in smokers (women) However, there have been mixed results which may be due to either different flavonol content in different brands or to the rapid biotransformation and elimination of tea catechins after ingestion Green Tea & Cancer Epidemiology Catechol-O-methyltransferase, COMT, allele codes for an enzyme with higher activity Individuals who possess at least one copy of the low activity COMT allele experience greater risk reduction with green tea consumption (even black tea provides some benefit) Mechanisms of Green Tea Action The major receptor for EGCG (67LR) is found on many tumour cells and its expression correlated with invasion and metastasis Treatment with EGCG slowed growth of tumour cells EGCG treatment of breast cancer cells leads to a down regulation of the 67LR protein Mechanisms of Green Tea Action Green tea polyphenols have been shown to affect several key regulators of cell cycle progression (a process of division allowing the duplication of cells; cancer is a “disease” of cell cycle progression) Green tea polyphenols combat virtually all aspects of tumour cell physiology (growth, proliferation, survival, lifespan and angiogenesis) http://mitworld.mit.edu/video/390/ Clinical Studies with Green Tea Oral green tea extracts equivalent to 7-8 cups of Japanese green tea three times daily shown to be safe, so clinical trials with extracts are underway Genistein & Cancer Genistein is an isoflavone (isoflavonoid) found in soy. Isoflavonoids and their physiological metabolites bind with high affinity to the estrogen receptor. Genistein is an inhibitor of protein tyrosine kinases, which is involved in cell cycle progression (tyrosine kinases show a high affinity to numerous growth signals, but this would not be good in a cancer cell). Genistein & Cancer Genistein, like other polyphenols, might prevent oxidation. Genistein is a good inhibitor of tumour necrosis factor-? activation (a potent immunomodulator and proinflammatory cytokine that has the potential to both kill some types of cancer cells as well as promote growth of other kinds of cancers). Genistein & Cancer Timing of the introduction of polyphenols is important. In a case-control epidemiological study using the Shanghai Cancer Registry, an inverse relationship between adolescent soy intake and breast cancer incidence later in life was observed. Other studies confirm that adult consumption of soy not associated with reduced risk of breast cancer. Genistein Activities Summary Estrogenic (a benefit to prostate cancer as well as breast cancer, but not for estrogen receptor-positive breast tumours) Antioxidant Anti-carcinogenic Anti-atherogenic Anti-osteoporotic Nutrients, Genes and Cancer Milly Ryan-Harshman, PhD, RD Cancer Themes: Online Lecture Articles Excessive energy intake Dietary fat Fruits and vegetables Dietary fibre Alcohol and caffeine Vitamin and mineral supplements Individual responsiveness Polymorphisms Feast or famine Nutritional genomics Improve research quality Identify at-risk populations Broaden cancer prevention strategies Green Tea Polyphenols & Cancer Prevention Camellia sinensis plant Three types of tea Black tea Green tea Oolong tea Green Tea Polyphenols & Cancer Prevention The methods of harvesting and processing of the tea leaves determines the type of tea and the kind of flavonoids present (see Figure 8.1 in text). Flavonol content varies little between three types, but catechins are affected by processing, so black tea contains theaflavins and thearubigens. Green Tea Polyphenols & Cancer Prevention Major catechins in green tea Epigallocatechin-3-gallate (EGCG) Epicatechin (EC) Epicatechin-3-gallate (ECG) Epigallocatechin (EGC) Green Tea & Cancer Epidemiology Improved prognosis of patients with breast cancer Green tea protection appears to function, in part, by reducing hormone levels associated with the risk of developing breast cancer Green tea reduces risk of cancers of the digestive tract Green Tea & Cancer Epidemiology Risk reduction for ovarian and prostate cancer Reduced risk of lung cancer in non-smokers, but no effect in smokers (women) However, there have been mixed results which may be due to either different flavonol content in different brands or to the rapid biotransformation and elimination of tea catechins after ingestion Green Tea & Cancer Epidemiology Catechol-O-methyltransferase, COMT, allele codes for an enzyme with higher activity Individuals who possess at least one copy of the low activity COMT allele experience greater risk reduction with green tea consumption (even black tea provides some benefit) Mechanisms of Green Tea Action The major receptor for EGCG (67LR) is found on many tumour cells and its expression correlated with invasion and metastasis Treatment with EGCG slowed growth of tumour cells EGCG treatment of breast cancer cells leads to a down regulation of the 67LR protein Mechanisms of Green Tea Action Green tea polyphenols have been shown to affect several key regulators of cell cycle progression (a process of division allowing the duplication of cells; cancer is a “disease” of cell cycle progression) Green tea polyphenols combat virtually all aspects of tumour cell physiology (growth, proliferation, survival, lifespan and angiogenesis) http://mitworld.mit.edu/video/390/ Clinical Studies with Green Tea Oral green tea extracts equivalent to 7-8 cups of Japanese green tea three times daily shown to be safe, so clinical trials with extracts are underway Genistein & Cancer Genistein is an isoflavone (isoflavonoid) found in soy. Isoflavonoids and their physiological metabolites bind with high affinity to the estrogen receptor. Genistein is an inhibitor of protein tyrosine kinases, which is involved in cell cycle progression (tyrosine kinases show a high affinity to numerous growth signals, but this would not be good in a cancer cell). Genistein & Cancer Genistein, like other polyphenols, might prevent oxidation. Genistein is a good inhibitor of tumour necrosis factor-? activation (a potent immunomodulator and proinflammatory cytokine that has the potential to both kill some types of cancer cells as well as promote growth of other kinds of cancers). Genistein & Cancer Timing of the introduction of polyphenols is important. In a case-control epidemiological study using the Shanghai Cancer Registry, an inverse relationship between adolescent soy intake and breast cancer incidence later in life was observed. Other studies confirm that adult consumption of soy not associated with reduced risk of breast cancer. Genistein Activities Summary Estrogenic (a benefit to prostate cancer as well as breast cancer, but not for estrogen receptor-positive breast tumours) Antioxidant Anti-carcinogenic Anti-atherogenic Anti-osteoporotic