Unit 2 Pathophysiology - Chapter 13 Cancer epidemoiology Flashcards
Dietary factors
r/t cancer development; how it interacts w/ genomics, epigenomics, transcription factors, proteomics (proteins), and metabolic factors => nutrigenomics
What can influence risks of developing cancer and other diseases?
What you eat, weight, and how much they move!
Food components w/ cancer preventing potential
- polyphenols
- selenium
- methyl group donors
- retinoids
- isothiocyanates
- allyl compounds
- mono- , poly- unsaturated fatty acids
Source of carcinogenic substances
cooking fat, meat or protein
plants - alkaloids or mold byproducts
Dietary components as mutagens?
Some components can act directly as mutagens or interfere w/ mutagen elimination
Dietary factors can affect what specfically?
cell cycle, differentiation, DNA damage and repair, stem cell renewal, hormonal axes, cellular proliferation, and cell death, cell signaling/inflammation/immunity
Xenobiotics
toxic, mutagenic, and carcinogenic chemicals found in human diet
What other food and nutrition tips can change carinogen metabolism?
sulforaphane (Sulforaphane is found in cruciferous vegetables like broccoli, cauliflower, and kale. It may offer anticancer, antidiabetes, and other benefits.) and isoflavonoids (Evidence suggests that eating a diet rich in soy foods may offer protection against certain cancers and cardiovascular disease. Isoflavones also appear to play a role in preventing bone loss — legume seeds or lentils, beans, peas)
Diets high in red meat and processed meat
colorectal cancer; N-nitroso compounds can increase nitogenous residues in colon and cause DNA damage
Undernutrition
factor in cancer d/t infectious agents
Obesity at risk for?
At risk for liver, advanced prostate, ovarian, gallbladder, kidney, colorectal, esophageal (adenocarcinoma), postmenopausal breast, pancreatic, endometrial, and stomach cancer.
lower body fatness lowers cancer risk for thyroid and multiple myeloma
3 main factors r/t to obesity and cancer
insulin-insulin-like growth factor axis, sex hormones, and adipokines (cytokines produced by adipose)
Obseity and metabolic changes
insulin resistance, hyperglycemia, dyslipidemia, hypoxia, anad chronic inflammation
Adipocyte dysfunction and obesity
secretions of abnormal levels of cytokines linked to insulin resistance, impairments in triglyceride storage and increases in lipolysis
adipocyte function as endocrine cells (alpha cells which secrete glucagon, beta cells which secrete insulin, and delta cells which inhibit the secretion on glucagon and insulin) and shape tumor microenvironment
Obesity and immune cell recruitment
increased cytokine production, inflammation, and fibrosis and reduced response to chemotherapy
obesity and aromatase expression
Aromatase is an enzyme that converts androgens into estrogens,
increased estradiol levels, promote growth of estrogen-dependent cancers
Warburg effect
tumors consume tons of glucose => to make cellular building blocks
Food metabolism and circadian cycles
linked; impairment of clock dysregulates metabolism
Alcohol and cancer
mouth, pharynx, esophagus, and liver; colorectal cancer in men and postmenopausal breast cancer
Factors that l/t alcohol-induced cancer developmetn
acetaldehyde (broken down from ETOH), oxidative stress, nutritional deficiency (folate and vitamin B)
Abberrant patterns (deviating) of DNA methylation
contribute to alcohol-induced carcinogenesis
Physical activity
reduce risk of breast cancer, colon cancer, and endo metrial cancer
Other protective effects of exercise
decrease insulin, IGF levels (aging)
* decrease obesity
* increase free-radical scavenger systems
* change inflammatory mediators
* decrease oncogenes
* decrease metabolic hormones and circulating sex hormones
* improve immune fx
* enhance cytochrome p-450 fx (detoxification and metabolism of foreign material and drugs) => modify carcinogen activation and increase gut motility
Exposure to outdoor air pollution and to particulate matter (PM in outdoor air
carcinogenic to humans and causes lung cancer; fine or ultrafine particles absorbed by lungs and phagocytosed by macrophages and neutrophils that release tissue-damaging inflammatory mediators
Mechanisms of adverse cellular effects d/t PM particulate matter
- cytotoxicity via oxidative stress
- ROS generation
- DNA oxidative damage
- mutagenicity (ability to induce mutagens)
- stimulation of proinflammatory factors
- induce cell senescence (eventually stop multiplying, don’t die off)
Indoor air pollution environmental tobacco smoke (ETS; passive smoking)
form reactive oxygen free radicals and thus DNA damage; ETS => human carcinogen
2012 Diesal exhaust
carcinogen as well
Central hypothesis for cancer pathogenesis via respiratory
- insoluble particles => pulmonary inflammation
- oxidative stress
- oxidation of DNA
- proliferative response => tissue remodeling via fibrosis
- tumor development
Atomic bomb exposure in japan
acute leukemias in adults and children; increased thyroid and breast carcinomas including lung, stomach, colon, esophageal, and urinary tract cancers + multiple myeloma
Ionizing radiation (IR) in radiation carcinogenesis
- initiator of premaligant cell clones
- promoter of preexisting premalignant cell alterations
Ionizing radiation
mutagen and carcinogen => penetrate cells and tissues and deposit energy in tissues @ random in form of ionizations
Exposure to ionizing radiation induces?…
apoptosis and senescence; evident in endothelial cells and radiation induced CV disease
innocent bystander cells
radiation may induce type of genomic instability to progeny of directly irradiated cells over many cell generations
Epigenetic events after radiation
altered pathways:
* cell adhesion
* extracellular matrix interactions
* cell-to-cell communication
Sun and UV radiation
basal cell carcinoma and squamous cell carcinoma
Intermittent acute sun exposure l/t
sunburn associated w/ increased risk of melanoma
degree of damage in skin
intensity and wavelength content - ultraviolet A (UVA) or ultraviolet B (UVB)
Pathogenesis of nonmelanoma skin cancers
involves:
* specific gene mutations
* DNA methylation and histone modifications
* oxidative stress
* inflammation
* reduced immune surveillance
Inflammation and ROS
ROS can induce # of transcription factors:
* activator protein 1 [AP-1]
* NF-KB
and increasea regulating genes that induce inflammation => critical in tumor progression
EMR controversey
non ionizing and low-frequency radiation
Radiofrequency-EMF
Electromagnetic field
possibly carcinogenic to humans
* genotoxicity
* impaired immune
* gene and protein expression
* cell signaling
* oxidative stress
* apoptosis
* blood-brain barrier
Certain viruses, bacteria, and parasite
main contributor to cancer worldwide (15.4% in 2012)
Helicobacter pylori (H pylori), human papillomavirus (HPV), hepatitis B virus (HBV), hepatitis C (HCV), and Epstein-barr virus (EBV)
top notable infection and cancer cases
EBV => affect a person’s blood and bone marrow. The virus can cause the body to produce an excessive number of white blood cells called lymphocytes (lymphocytosis). EBV can also weaken the immune system
Large majority of liver cancer diagnoses
Hepatitis B and hepatitis C
Reproductive tract viral infection
HPV; most for both genders will be infected at some point and may be repeatedly infected
75% of stomach cancer
H. pylori
EBV
associated w/ subset of hodgkin lymphoma (white blood cells called lymphocytes grow out of control, causing swollen lymph nodes in neck, chest, or armpits, and growths throughout the body) and burkitt lymphoma (non-Hodgkin lymphoma, cancer of lympathic system, makes abnormal B lymphocytes, start anywhere in the body)
If a specific type of cell called a Reed-Sternberg cell is seen, the lymphoma is classified as Hodgkin’s. If the Reed-Sternberg cell is not present, the lymphoma is classified as non-Hodgkin’s. Many subtypes of lymphoma exist.
HPVs
13 are cancer causing; types 16 and 18 - high risk or oncogenic cause 70% of cervical cancers and precancerous cervical lesions
also linked w/ anus, vulva, vagina, and penis cancer
infection w/ HPV-16 precedes several years diagnosis of oropharyngeal cancer
Factors that inc risk for cancer following high-risk HPV infection
smoking, decreased immunity, having multiple children, long-term oral contraceptive, poor oral hygiene, chronic inflammation
