Diet and Cancer PDF

Diet and cancer: colorectal and breast cancer Pr. Roberta FORESTI Professor of Biochemistry, Faculty of Health, UPEC [email protected]  Cancer Cancer is defined as a disease in which the normal co...

Diet and cancer: colorectal and breast cancer Pr. Roberta FORESTI Professor of Biochemistry, Faculty of Health, UPEC [email protected]  Cancer Cancer is defined as a disease in which the normal control of cell division is lost, so that these cells will multiply inappropriately to form a tumor. The tumor may eventually spread through the body and overlwhem it, causing death. Cancer has been found since the beginning of history (Egyptians) but has significantly increased in the last 120 years, due to an increase in the aging population. Cancers in Western industrialized Cancers in developing countries countries Lung Lung Stomach Colorectal Breast Breast Liver Prostate BMJ 1999;319:505 Various factors can cause cancer, including tobacco, alcohol, ionising radiation, ultraviolet light, certain infections and hormones. These are all non-dietary factors that are causes of cancer (excluding alcohol). Dietary factors are thought to be important determinants for the risk of developing cancer, but it is very difficult to establish the exact effects of diet on cancer and the importance of only few dietary factors is clearly established. In France in 2018, while men still had higher risks of developing or dying from most cancers, the sex gap was narrowing. Efforts should focus on avoiding risk factors (e.g., smoking) and developing etiological studies to understand currently unexplained increasing trends. BMC Cancer volume 21, Article number: 726 (2021)  Diet and cancer Determining the effects of diet on cancer is difficult different dietary factors may both increase or decrease the risk of developing cancer the size effect of the risk may be small (less than 2 fold), compared to the large effects of some agents, such as smoking (heavy smoking increases risk of lung cancer by 30 folds, HPV infection increases the risk of cervical cancer by 100 fold) inaccuracy of estimates of dietary intake interrelations of most foods and nutrients in the diet narrow range of food choices in populations biases in recall of food intake https://www.anses.fr/en/system/files/NUT-QR-NutritionCancerEN.pdf  Diet and cancer Cancer causation: Initiation. Inititiation occurs in one single cell - DNA mutation -. Diet may play a role, for ex. burnt food, nitrates and derived compounds found in some smoked and processed food - dietary mutagens -. Well-established is the role of aflatoxin, food contaminat produced by Aspergillus fungus, which can be found in grains, oilseeds, nuts and dried fruits stored in hot and humid conditions. Promotion. Fat and protein help in promoting the growth of cancer. Progression. At this stage the only treatment is surgery or chemotherapy. Diet has no major influence even if studies are considering the role of diet and lifestyle in the recurrence of cancer in survivors. Although a role of alcohol in cancer is well-established, the mechanisms are still not clear. https://www.wcrf.org/ https://www.iarc.who.int/  Diet and cancer: epidemiological studies Comparisons in populations. Statistics of incidence, mortality, risk. Compare and assess environmental factors/ difference in nutrition, diets, nutrients. Ex. Cancer incidence vs meat consumption (correlation studies). Or check subgroups: vegetarians or no alcohol drinking vs the rest of the population. Studies on migrants. Provide effects of environmental exposures (as opposed to genetic factors) on cancers rates. Ex cancer rates in migrants increase in host country (Japanese living in Hawaii have higher colon cancer). Confounding: is the lifestyle maintained in host country? Is diet the only other environmental factor that changed? Case-control studies. Compare patients with cancer (cases) and group of people without cancer (controls) in the same population. Limitations! Selection of controls, dietary data collected retrospectively (misreporting, not accurate…) Prospective studies. Large group of individuals assessed at the beginning of the study (diet, blood samples etc.) and followed over time (10 years or more). Examine the dietary characteristics of those who develope cancer vs those that do not. Mostly done in the USA, in Europe we have the EPIC study. To date: 1,818 publications on the role of diet and cancer (and other diseases, metabolic syndrome, diabetes etc.)  Diet and cancer: epidemiological studies Controlled trials. Best possible studies! Specifc dietary constituents (micronutrients) and risk of disease - intervention group: receiving dietary constituent - control group: receiving inactive placebo Randomised and double blind (not possible with food!) Endpoint - Cancer development? - Intermediate biomarker? Difficult to do: 1) ethical reasons 2) people do not stick to prescribed diets 3) control group might want to eat healthy to reduce risk of cancer  Diet and cancer: epidemiological studies Meta-analyses. A statistical synthesis of data from separate but comparable studies leading to the assembly an of several data that are statistically analyzed and critically evaluated. Usually meta-analyses are conducted for randomised controlled trials and prospective cohort and case control studies.  Stomac cancer Salt/salty foods High salt intake irritates the gastric mucosa, resulting in inflammation. This affects DNA synthesis and cell proliferation Fruits and vegetables Antioxidants, carotenoids, vitamins C and E Dietary fibre This combination is protective against stomac cancer  Colon cancer Colorectal cancer is the second most common cancer in the West Migrants acquire incidence rates of host country Non-dietary factors: susceptibility genes, physical activity Colon cancer Colorectal cancer: fruits and vegetables Moderate consistent evidence for protection by increasing vegetables and fruit in diet Colorectal cancer: dietary fibres and whole grain Colorectal cancer: dietary fibres and the Burkitt hypothesis Burkitt hypothesis: in the lateb 60s, working in Uganda, Burkitt noticed that typical diseases of England were uncommon in the Ugandan population. In Uganda the diet was rural, with lots of bulky foods rich in fibres. He noticed that stools of Ugandan people were much bigger than stools of English people, so he suggested that the poor fibre content in the English diet was responsible for the high incidence of colorectal cancer (and the inverse in Uganda). Dietary fibre intake in HICs is around 15 g/day (well below the amount of fibre Burkitt advocated of >50 g/day) Colorectal cancer: meat Consumption of red meat is probably a cause. Meat intake and low fruits/vegetables? Consumption of processed meat is a convincing cause.  Colorectal cancer: mechanisms Dietary fibre - Fermentation to short chain fatty acids (anticancer activity) - Reduces intestinal transit time, reducing the potential for fecal mutagens to interact with the colon mucosa - Reduction in insulin resistance, a risk factor for colorectal cancer Fruits and vegetables - antioxidants and vitamins C and E and carotenoids - folates - selenium - dietary fibres Meat and processed meat - rich in fat - cooking at high temperature, producing toxic compounds - N-nitroso compounds in processed meat may also increase cancer  Breast cancer Breast cancer is the most common cancer in women worldwide Susceptibility genes (BRCA1 and BRCA2) increase risk (5-10% of all breast cancers) Other risk factors Hormonal and reproductive-early menarche, late menopause, age at first birth, estrogen replacement therapy, obesity post-menopause Migration from low risk areas to high risk areas results in women acquiring the risk of the host country (increase) within one to two generations, implicating environmental factors Breast cancer Average age of menarche in girls = 12-13 years Average age of menopause = ~ 51 years  Breast cancer: alcohol Drinking alcohol — in any form — raises breast cancer risk. Alcohol limits (maximum): 10 g/d women 20 g/d men 10 g alcohol corresponds to ca. 250 ml beer 125 ml wine 30 ml liquor  Breast cancer: body fatness Body fatness appears to be protective in pre-menopausal cancer but is an important risk factor for post- menopausal breast cancer  Breast cancer: mechanisms Alcohol - alcohol influences blood levels of estrogen and other hormones in ways that may make cancer more likely - alcohol is a recognized carcinogen. It can cause cellular damage that can trigger cancer development - heavy alcohol intake is associated with inadequate intake of essential nutrients Weight and body fatness in post-menopausal breast cancer - fat tissue causes inflammation, which can promote cancerous changes in healthy cells - being overweight and obese increases blood levels of insulin and related hormones that can encourage the growth of cancer