CANCER Flashcards
(51 cards)
What is Cancer?
Diseases characterized by:
- uncontolled cell growth caused by genetic mutations and epigenetic alterations in gene transcription
- spread of abnormal cell throughout the body (metastasis)
Carcinogenesis
Initiation
normal cell (melanocyte)
**Cell DNA altered **
- chemicals, radiation, and viruses can alter cell DNA (in this case, radiation from the sun is the likely cause)
- altered cell-this can grow into a cancer
Promotion
inc. cell division-this is needed to promote the cancer process
**cancer cells **
Further Progression
- cancerous tumor (malignant melanoma)
“Cancer” can refer to either a benign or a maglignant tumor.
A) True
B) False
B) False
Maglignant cells
- invade neighboring tissues, enter blood vessels, and metastasize to different sites
- spread throughout the body
Begnign tumor
not cancer
- cells grow only locally and canot spread by invasion or metatasis
- resticited grwoth doens’t spread
The breat cancer risk genes BRCA1 and BRCA2 are:
A) oncogenes/proto-oncogenes
B) Tumor supressor genes
C) Genes invovled in estrogen metabolism
B) Tumor suppressor genes
Tumor Supressoe Genes
DNA methylation patterns cause loss-of-function effects that contribute to the maligant phenotype
- gene silenced
Oncogenes
DNA methylation patterns alternations cause gain-of-function
- gene active
What are molecular changes in cancer?
- inhibition of tumor suppressor genes
- activation of oncogenes
- changes in signal transduction pathways
- chromosomal rearrangements
- genome instability
Three-stage Carcinogenesis
Initiation: ranges from minutes to days (short)
- Cancer causing agent
- No DNA repair, impaired regulation of apoptosis
Promotion: may last months or even years
- Altered DNA leads to changes in gene expression, protein
function, etc.
- Cell proliferates in uncontrolled way
- Alcohol, estrogen in breast tissue, Helicobacter pylori in the stomach,
HPV in cervix may act as promoters
Progression
- Malignant cells invade surrounding tissue and metastasize to other sites
How does genetic alteration causes these changes in cancer?
Point mutations
Polymorphisms
Copy number variants
- Genetic predisposition may only account for ~5-10% of risk for cancer
E.g., BRCA1 and BRCA2 are hereditary breast and ovarian cancer
- 55-65% of women with a harmful BRCA1 mutation and 45% of women with a harmful BRCA2 mutation will develop breast cancer by age 70 years (12% risk in general population)
- 39% of women with a harmful BRCA1 mutation and 11-17% of women with a harmful BRCA2 mutation will develop ovarian cancer by age 70 years (1.4% risk in general population)
- mutation in these genes inc. the risk of breast cancer, but doesn’t nessarily mean everyone w/ mutation get cancer
BRCA1 and BRCA2 Mutations
- missing protein
- non-functional protein
Defective: - DNA repair
- Trancription
- G2/M cell cycle checkpoint regulation
- spindle checkpoint
How do we know factors other than genetics contribute to cancer risk?
Environmental factors
Colon cancer higher in U.S compared in Japan, but similars cases in Japanese families in U.S
Stomach cancer higher in japan compared to U.S and Japanese families in U.S
How does epigenetic alternations causes these changes in cancer?
DNA methylation
Histone covalent modifications
microRNAs
- which genes are expressed and non-expressed
- epigenome responds to the environment - abrasions can cause functional changes
What is epigenetics?
The study of heritable changes in the phenotype or gene
expression caused by mechanisms other than changes in DNA
sequences
E.g., Genetics vs Epigenetic
- writing and reading
- musical notes and melody
- computer and software
Examples: A twin approach to unravelling epigentics
Identical twins who were given up for adoption to different
families at birth and only discovered this in their mid-30s.
- Identical twins start with the same genetic make-up but over time in phenotype they drift apart
- Epigenetic variation as a dynamic quantitative trait
- High monozygotic twin discordance rates for common diseases
Epigenetics alterations and disease state
Autoimmune and inflammatory diseases
Rheumatoid arthritis
Inflammatory bowel disease
Multiple sclerosis
Diabetes
Lupus
Aging
Parkinson’s disease
Alzheimer’s disease
Cardiovascular disease
Behavioral and psychiatric disorders
(Schizophrenia, Autism, Anxiety, ADHD)
Chronic pain
Components of epigenome
DNA methylation
Non-coding RNA (microRNA)
Histone modifications
DNA methylation and gene activity
addition of methyl group to DNA by DNA methyltransferase to stabilize the chromatin and dynamic
**Unmethylated CpG island **
- gene expressed
**Methylated CpG island **
- trancription factors can not bind and completed silenced
Hypermethylation
silencing
Hypomethylation
activation
Nutrition and the epigenome
diet provides folic acid, betaine, choline, B vitamins, and methionone to synthesize in the SAM in the body
- regulate methylation; methyl groups
Bioactive componds in fruits, vegetables, and spices
Genistein
- soy, tofu
Pterostilbene
- blueberry
Resveratrol
- grapes
Sulforaphane
- broccoli
Functional benefits of nutritional epigenetic effects
- Decrease in cell proliferation
- Decrease in cell migratory and invasive properties
- Inhibition of oncogenic signaling pathways