Lernkarten

Cancer development

• can be somatic or inherited --> 90% somatic
  • functional gene on one of both chromosome pairs can compensate for mutation on other, e.g.: inherited mutation from mother can be compensated via euivalent gene inherited from father --> loss of function of both genes that will result in cancer
• 3 phases: initiation, promotion and progression
• cancer risk accumulates over time and is therefore higher in aged individuals
  • may affect all ages though
• Cancer types
  • benign: slow cell multiplication
  • maligng: invades and destroys surrounding tissues, rapid cell growth
  • metastasis: affects multiple organs as cancerigenous cells spread throughout body
• process requiring lots of time: cell's repair mechanisms (p53) are defect --> mutation is not corrected and persists in daughter-cells  --> becomes cancer / malignant as soon as cells multiply and invade other tissues
  • bad-luck-theroy: cells with high turnover are more susceptible to DNA errors
  • p53: guardian of the genome
    • mutated in >50% of cancers --> precancerous cells esacape apoptosis pathways (=quality control)
    • induces apoptosis if DNA errorr is detected

Cancer prevalence

• most frequent cancers vgl Bild
  • cancer patterns--> cancer type and total prevalences differ between countries
    • suboptimal food storage (curing --> high salt ; no fridge --> mold (aflatoxin)
    • LMIC affected by cancers related to poverty and infections --> digestive tract affected
    • high income countries: lung (smoking?), breast prostate (hormonal imbalances)
    • lifestyle factors: much higher cancer prevalences overall --> many-fold or less many-fold increase depending on cancer type (vgl. slide 36)
• mortality lower in high income countries because of treatment options
• Trend predicts stabilization of prevalence but increase in total numbers because of increase of world population
• comparison between countries only possible with proper age-standarization --> higher aged associated with greater risk, so age needs to be accounted for

Lifestyle factors

• migrants studies: people with same genetic background living in different environment, on population level
• twin studies: as migrant studies but on an individual or lower scale level
• correlational studies: e.g. meat intake vs cancer prevalence or cancer deaths
  • will inly show trends, not highest quality data
  • national and international levels possible --> std for age imporant for comparison
• Time-trend studies: ??
• case-control: ??
• intervention studies: ??
• Cohort studies
  • current state of the art in cancer research
  • FFQ + biomarkers used
  • long-term, prospective studies

Tools

• questionnaires: food, lifestyle and risk factors such as e.g. smoking
  • carcinogens usually found in toxicology and mechanistic studies --> informs questionnaires (and vice versa)
• biomarkers: b-carotene

Nutrition

• body / cell require nutrients for cell cycle and proper functioning
• Hormonal imbalances drive cancer development
  • overfeeding, diabetes --> fats and sugars
  • obesity second largest known risk factor for cancer
    • waist circumference correlates with breast cancer
    • weight loss reduces risk of cancer
    • often accompanied by other cancer promoting states --> inflammation, lack of fibre ==> obese cancer patients are more likely to die of cancer due to obesity (or other way around?)
  • menopause: increase in risk due to changes in hormones --> lower pre-menopausal risk for same cancer type (breast)
  • pregnancy: hormonal changes during/after pregnancy protect women
• hallmarks activated via obesity
  • insulin resistance as key driver of cancer
    • increase in estrogen due to reduced SHBG --> estrogen-dependent tumors
    • higher IGF1 levels
    • hyperglycemia --> anaerobic oxidation = cancerigenous
    • inflammation
• importance of exercise
  • reduces inflammation, improves insulin sensitivity, stabilizes weight
  • convincing evidence for reduces colon cancer

Multiple nutritional factors influence cancer risk

• Increase risk
  • Red and processed meats: 1.2% increase
    • Red and processed meats increase risk for colorectal cancer, white meat and fish decrease it marginally
    • Nitrosamines, saturated fats and ROS stress due to heme as potential drivers
  • Alcohol
    • Genotoxicity of acetaldehyde + other à vgl Bild
    • Increases risk for many cancers
    • Decreases risk for kindey cancer
• Decrease risk
  • Dairy and fish decrease certain cancer risks à vgl Bild
  • Fibre
    • Overall chance of contact between carcinogens & enterocytes is reduced
      • Faster transit times
      • Binding of carcinogens
      • Greater bulk à lower likelihood of contact
    • Reduce insulin resistance
    • Bioactive compounds of wholegrains
  • Fruit
    • Decrease in cancer risk limited

Cancer prevention

• Individual level
  • Healthy weight and physically active
  • Diet rich in fruits, vegetabes and beans
  • Limit intake of SSB, red meat, fast food, alcohol
  • Do not use supplements for cancer prevention
  • Breast feed
• Government
  • Incentives to fruit and vegetable consumption
  • Clear nutritional labels
  • Nutritional education and personalized advice
  • Healthy meals for the masses à schools, workplaces, institutions

Micronutrients

• B-carotene
  • Plasma levels have sotrnger correlation with cancer prevention than dietary intake à shows that plasma markers are more reliable
  • Supplementation increased cancer incidence in asbestos workers and smokers
    • B-carotene not recommended for cancer prevention, backed up by meta-analysis
    • Doses of 20-30mg/d
    • study had to be stopped
    • no deleterious effects observed with vit A and E
• Folate
  • Double edged sword: due to methylation, folate can promote cancer growth once tumorous cells have developed
  • Higher intake not found to increase cancer risk in 5.5y RCTs yet
  • Epidemiological studies show inverse relation between intake and development of colorectal cancer

CVD epidemiology

• CH
  • CVD: increasing rates ever since population infectious diseases could be prevented/reduced --> opulations ages and becomes prone to CVD
    • Since 1980 and current trend: declining CVD mortality --> CH one of the highest ranking countries in terms of ortality because time to reach hospital after event is short and treatment excellent
    • cancer: trend remains stable
  • mortality vs.  incidence values available for CVD
    • changes in mortality are due to treatment or screening --> decrease in mortality due to improvements in treatment
    • changes in incidence reflect efficacy of preventive measures
    • CH: decreasing mortality but increase in incidence, especially for males --> treatment has improved, preventive measures seem ineffective
  • Age as an important factor for CVD: mortality increases as of 65, at 85+ becomes most common cause of death
    • individuals <65 can still suffer from CVD
  • death remain stable while hospitalization is increasing --> screening improved? (slide 8)
    • healthcare and socioeconomic burden big, despite decreasing mortality
  • Regional and societal differences
    • higher class less prone to CVD --> also less smokers
    • Romandie less affected than Deutschschweiz
• International
  • trends also declining
  • similar trends in US, DE, FR, and CH
  • Switzerland ranks amongst lowest CVD mortality countries --> treatment and screening efficacous