Carcinogenesis Flashcards
Cancer is a ___ disease
Genetic
Cancer involves the ___ of the cell
Alteration
1/3 of cancer deaths are from modifiable factors such as…
-Tobacco
-Weight
-Alcohol
-Fruit and vegetable intake
-Physical activity
30% of cancer results from cancer-causing infections like…
-HPV
-Hepatitis
The best chance of cure is through what two things?
-Early detection
-Effective treatment
It is estimated that ___ million new cases of cancer will be diagnosed in 2022
1.9
What are the three most prevalent forms of cancer in men?
-Prostate cancer (26%)
-Lung cancer (12%)
-Colon and rectal cancers (8%)
What are the three most prevalent forms of cancer in women?
-Breast (30%)
-Lung (13%)
-Colon and rectal (8%)
What 3 types of cancer cause the most deaths in men?
-Lung (22%)
-Prostate (11%)
-Colon and rectal (9%)
What 3 types of cancer cause the most deaths in women?
-Lung (22%)
-Breast (15%)
-Colon and rectal (8%)
There have been many strides made with some cancers with immunotherapy, but ___ cancer is usually diagnosed late (new tools are being developed to help screen earlier
Lung
Carcinogenesis is also known as…
-Oncogenesis
-Tumorigenesis
Cancer occurs due to the ___ of normal cells
Transformation
The process of carcinogenesis includes changes at a ___, ___, and ___ level and abnormal cell division
Cellular, genetic, and epigenetic
Normally, there is a balance between cell ___ and cell ___ (in the form of apoptosis)
Proliferation and death
According to the prevailing accepted theory of carcinogenesis, the ___ ___ ___, mutations in DNA and epimutations that lead to cancer disrupt these orderly processes by disrupting the programming regulating the processes of cell proliferation and cell death
Somatic mutation theory
The upset in the balance between cell proliferation and cell death results in ___ cell division and the evolution of those cells by natural selection in the body
Uncontrolled
Only certain ___ lead to cancer whereas the majority of them do not
Mutations
Ancient ___ thought of cancer as a curse
Egyptians
In 3000 BC, Edwin Smith Papyrus discovered ___ cancer
Breast
In 1500 BC, Ebers Papyrus discovered what types of cancer?
-Skin
-Uterus
In the 16th century, ____ discovered the 1st correlation between the environment and cancer
Paracelsus
In 1914, Theodor Boveri was the 1st to hypothesize that segregation of chromosomes to ___ cells leads to tumor development
Dgt
Ancient people used to think that ___ bile cancers were incurable and ___ bile cancers were curable
Black, yellow
___ was the first to use the word “cancer” to describe tumors
Hippocrates
Cancer is derived from the Greek word “karkinos” which means ____
Crab
It is thought that Hippocrates was referring to the appearance of ___, with the main portion of the tumor being the crab’s body and the various extensions of the tumor appearing as the legs and the claws of the crab
Tumor
Cancer is caused by ___ of DNA that lead to cellular damage
Mutations
Mutations enable cancer cells to divide continuously, without the need for normal ____
Signals
In some cancers, the unchecked growth results in a ___ called a tumor
Mass
Cancerous cells may invade other parts of the body, interfering with ___ ___ ___
Normal body function
____ tumor cells grow only locally and cannot spread by invasion or metastasis
Benign
____ tumor cells invade neighboring tissues, enter blood vessels, and metastasize to different sites
Malignant
Progression of carcinogenesis (5 steps):
-Mutation inactivates suppressor gene
-Cells proliferate
-Mutations inactivate DNA repair genes
-Proto-oncogenes mutate to oncogenes
-More mutations, more genetic instability, and metastatic disease
The microenvironment may help the cancer cells grow; ____ increases the blood supply and this feeds the cells so that they are able to continue to grow
Angiogenesis
A ____ mutation is one that exchanges one base for another which would encode a different amino acid and cause a small change in the protein produced
Substitution
___ ___ ___ is caused by a substitution in the beta-hemoglobin gene, which alters a single amino acid in the protein produced
Sickle cell anemia
If there is a change in a codon to one that encodes the same amino acid and causes no change in the protein produced, this is called a ___ ___
Silent mutation
If there is a change in a codon to one that encodes a ____ codon, this would cause an incomplete protein and can have serious effects since the incomplete protein would most likely not function
Stop
____ are mutations in which extra base pairs are inserted into a new place in the DNA
Insertion
____ are mutations in which a section of DNA is lost or deleted
Deletion
In ___ mutations, the DNA is parsed wrong which usually generated proteins that are useless and uninformative (caused by insertions or deletions)
Frameshifts
While many mutations have small effects, mutations to ___ ___ can have major (and sometimes even positive) effects
Control genes
Control genes control other genes, determining when and where other genes are turned ___
On
Mutations in parts of the gene that control other genes can substantially change the way an organism is ____
Built
Mutations to control genes can cause a cascade of effects in the ____ of genes under its control
Behavior
Most mutations have no ___ because they either do not affect the function of the cell, are repaired by DNA repair genes, or are lost as a result of the death of a cell
Consequences
Mutation of genes that control the growth or that protect the stability of the genome may result in a clone of cells with ___ ____
Growth advantage
Successive mutations of these genes result in increasingly different clones until a ___ phenotype eventually emerges
Malignant
What are the two basic kinds of genetic mutations?
-Germline mutation
-Somatic mutation
A germline mutation is responsible for ___% of cancer cases and is heretible
15
Somatic mutations are random mutations from ____ influence
Carcinogenic
____ mutations result in most cancer cases
Random
Only ___-___% of mutations result in cancer
5-10
Since all cells in our body contain DNA, there are lots of places for mutations to occur, however, some mutations cannot be passed on to offspring and do not matter for ___
Evolution
A single germline mutation can have a range of effects, like…
-No change occurring in phenotype
-Small change in phenotype
-Big change occurs in phenotype
Some mutations don’t have any noticeable effect on the phenotype of an organism; this can happen if the mutation occurs in a stretch of DNA with no ___, or the mutation occurs in a protein-coding region but ends up not affecting the amino acid sequence of the protein
Function
Some very important phenotypic changes are caused by a single mutation, like ___ ___ in insects
DDT resistance (pesticide)
Mutations that cause the death of an organism are called ____
Lethals
__ __ ___ are single-nucleotide substitutions of one base for another; they occur in more than one percent of the general population
Single Nucleotide Polymorphisms (SNPs)
SNPs are the most ___ type of genetic variation
Common
Each SNP represents a difference in a single DNA building block, called a ____
Nucleotide
SNPs occur through a person’s DNA about once every ____ nucleotides on average, which means that there are roughly 10 million SNPs in the human genome
300
Most commonly, SNPs are found in the DNA between ____
Genes
SNPs can act as biological markers, helping scientists locate genes that are associated with ____
Disease
When SNPs occur within a gene or in a regulator region near a gene, they may play a more direct role in disease by affecting the gene’s ____
Function
Most SNPs have mo effect on health or development, but many have proven to be very important in the study of ___ ___
Human health
Researchers have found SNPs that may help predict…
-Someone’s response to certain drugs
-Susceptibility to environmental factors such as toxins
-Risk of developing particular diseases
SNPs can also be used to track ___ of disease genes within families
Inheritance
Some SNPs generate ____ variation between people (some lead to differences in health or appearance, most have no observable changes)
Biological
Not all single-nucleotide changes are SNPs, though; to be classified as a SNP, two or more versions of a sequence must each be present in at least ___% of the general population
1
SNPs can happen in the cell line responsible for…
-Genes encoding proteins involved in drug transport and metabolism
-DNA repair
-Encoding drug targets and proteins involved in oncogenesis and cell signaling
If SNP happens in a cell, it results in a code for a different protein which can lead to the evolution of a cancer’s inability to respond to a ___
Drug
In human beings, ___% of bases are the same the the remaining percentage is what makes a person unique
99.9%
The variations in humans can be…
-Harmless (change in phenotype)
-Harmful (diabetes, cancer, heart disease, Huntington’s Disease, hemophilia)
-Latent (variations found in coding and regulatory regions, are not harmful on their own, and the change in each gene only because apparent under certain conditions, like susceptibility to lung cancer)
SNPs in genes involved with DNA repair and drug-metabolizing enzymes which are responsible for metabolism and detoxification of ____ can as act cancer susceptibility genes through the activation of chemical carcinogens and decreased ability of a cell to detox and repair mutagenic damage
Carcinogens
____ mutations cause alteration of large amounts of DNA, often on the level of the chromosome by moving one part of a chromosome to a different chromosome
Translocations
What two types of cancer are caused by translocation mutations?
-Leukemia
-Lymphoma
___ ___ is when there is production of many copies of a gene or set of genes at one location on a chromosome
Gene amplification
____ are segments are DNA that are released from a chromosome that are then re-inserted in the opposite orientation
Inversions
____ is the loss of gain of an entire chromosome
Aneuploidy
____ changes are changes to the DNA and chromatin that do not change the sequence
Epigenetic
A ____ mutation is an alteration of one or a few base pairs (transition or transversion mutation)
Point
A ___ ___ mutation causes larger effects (insertion or deletion)
Frame shift
A chromosomal translocation in the bone marrow is associated with ___ ___ ___
Chronic myelogenous leukemia (CML)
The ____ chromosomes is very common in chronic myelogenous leukemia
Philadelphia
If you find a mutation, you are better able to target the ____
Treatment
____ ____ are most often hematologic malignancies and are generally caused by chromosomal translocations, but sometimes bu chromosomal inversions
Chromosomal rearrangements
Sometimes, the same ____ appears in several different locations
Proto-oncogene
Whar types of cancer are caused by chromosomal rearrangements?
-Burkitt Lymphoma (85%)
-T cell acute lymphoblastic leukemia
Point mutations occur most often in the ___ family (K-ras, H-ras, N-ras)
Ras
K-ras carcinomas are responsible for…
-30% of lung adenocarcinomas
-50% of colorectal cancer
-90% pancreas
N-ras is responsible for ____ malignancies
Hematologic
K-ras, H-ras, and N-ras can all cause ____ cancer
Thyroid
What are three important factors in genetic alteration?
-Proto-oncogenes/oncogenes
-DNA repair genes
-Tumor suppressor genes
An oncogene is a _____ that has been mutated
Proto-oncogene
Proto-oncogenes stimulate the cell to ____, ___, and move through each cell cycle checkpoint to be inspected
Grow, divide
If a proto-oncogene mutates, it becomes an oncogene and no longer stops at cell ____ to ensure its normal
Checkpoints
___ ___ genes act to stop cell growth
Tumor-suppressor
DNA repair genes fix ____
Errors
Oncogenes are bad and turn ___ ___ ___ on
Abnormal cell growth
There are about ____ proto-oncogenes in our DNA
70
Oncogenes are mutated genes whose ____ can stimulate the development of cancer
Presence
Oncogenes are “___ ___ ____” genes that gain the ability to drive non-stop growth
Gain of function
A single mutated oncogene is usually not enough to cause ____ all by itself because tumor suppressor genes are acting to stop the growth from getting out of control
Cancer
Oncogenes aren’t usually involved in ____ forms of cancer because most occur as comatic mutations and can’t be passed down
Inherited
____/___ is an oncogene that encodes for a cell surface receptor that can stimulate cell division; this gene is amplified in up to 30% of human breast cancers
HER-2/neu
____ overexpression has been associated with a number of cancers including lung cancer, anal cancers, and glioblastoma multiforme; these are somatic mutations involving this gene that lead to its constant actuation, which leads to uncontrolled cell division
EGFR
The ___ oncogene products are involved in kinase signaling pathways that ultimately control transcription of genes, regulating cell growth and differentiation
Ras
The ____ oncogene is a transcription factor and controls expression of several genes
MYC
The ____ was the first oncogene discovered; the protein is a tyrosine kinase, which regulates cell activity
SRC
The ____ oncogene codes for an enzyme (telemerase) that maintains chromosome ends (telomeres)
hTERT
Tumor suppressor gene act as a braking signal during phase ___ of the cell cycle to stop or slow down the cell cycle before the S phase (if tumor suppressor genes are mutated, normal break mechanisms will be disabled, resulting in uncontrolled growth)
G1
Mutations in tumor suppressor genes cause ___-___-___ mutations
Loss of function
Loss of function mutations generally only show up when ___ copies of the gene are mutated (when there is a pair of tumor suppressor genes mutated, this might allow cancer to develop)
Both
Individuals who inherit an increased risk of cancer are often born with one ___ ___ of a tumor suppressor gene (if the second copy becomes mutated, then the person may develop cancer because there is no longer any functional copy of the gene)
Defective copy
____ is a tumor suppressor gene that regulated cell division and cell death
p53
___ is a tumor suppressor gene that alters the activity of transcription factors and therefore controls cell division
Rb
____ is a tumor suppressor gene that controls the availability of a transcription factor
APC
DNA repair genes code for proteins whose normal function is to correct errors that arise when cells duplicate their DNA prior to ___ ___
Cell division
DNA repair genes are active throughout the cell cycle, particularly during ___ after DNA replication and before the chromosomes divide
G2
Certain forms of hereditary ___ cancer involve defects in DNA repair genes
Colon
Two very important DNA repair genes are ___ and ____ which are most known in relation to breast cancer
BRCA1 and BRCA2
BRCA1 and BRCA2 are also big in ___ and ___ cancer
Ovarian and pancreatic
___-___% of pancreatic cancer have a BRCA gene mutation
10-15
For decades, doctors believed that cancer was caused by irreversible damage to some critical stretch of DNA within one’s genome, but some cancers are actually caused by ___ ___ that are caused by tiny chemical tags that accumulate over time and can turn genes on or off
Epigenetic changes
Unlike genetic damage, epigenetic changes can sometimes be ____, and with treatments that are far less toxic to the patient
Reversed
After 9/11, there was an increase in ___ ___ from benzene from the jet fuel which caused a chemical tag that coils around the histone (this is an epigenetic change)
Mylodys Syndrome
Another example of an epigenetic carcinogen is ____, which is a drug that was found to be damaging to fetuses when given to pregnant women
Diethylstilbestrol (DES)
Epigenetics can also alter gene expression by changing…
-DNA methylation (abnormal methylation has been seen in cancer cells)
-Histone acetylation (when histones squeeze DNA tightly, they hide the gene which renders it un-usable)
-Altered expression non-coding RNA
Epigenetics can be ___ mutations, meaning they drive the progression of cancer
Driver
Epigenetics can also be ___ mutations, meaning they are just random events
Passenger
Methylation changes are thought to occur more ____ than mutations in the DNA, and so they may account for many of the changes during the neoplastic progression, particularly in the earlier stages
Frequently
What are two examples of demethylating agents used to treat Myelodysplastic Syndrome (MDS)?
-Azacitabine (Vidaza)-> orphan drug, meaning it has been developed specifically to treat a rare medical condition
-Decitabine (Dacogen)
What is a demethylating agent used in the treatment of cutaneous T-cell lymphoma?
Vorinostat (in clinical trial)
What are three functions of proto-oncogenes?
-Regulates cell growth and differentiation
-Signal transduction
-Execution of mitogenic signals
Steps of oncogenesis (starting from healthy cell):
-Healthy cell
-Damage
-Overgrowth
-Cell transforms to a cancer cell
-Cancer cells replicate
Hanahan and Weinberg originally described ___ principle cellular traits shared by virtually all forms of human cancers which collectively, dictate tumor development and growth
6
What are the original 6 Hallmarks of Cancer?
-Self-sufficiency in growth signals (activate H-Ras oncogene)
-Insensitivity to anti-growth signals (lose Rb suppressor)
-Evading apoptosis (produce IGF survival factors)
-Sustained angiogenesis (produce VEGF)
-Limitless replicative potential (turn on telemorase)
-Tissue invasion and metastasis (inactivate E-cadherin)
The 7th Hallmark that is soon to be added is…
Ability to invade the immune system
The current 10 hallmarks of cancer:
-Sustaining proliferative signaling
-Evading grow suppressors
-Avoiding immune destruction
-Enabling replicative immortality
-Tumor-promoting inflammation
-Activating invasion and metastasis
-Inducing or activating vasculature
-Genome instability and mutation
-Resisting cell death
-Deregulating cellular metabolism
What are 4 new emerging hallmarks/enabling characteristics?
-Unlocking phenotypic plasticity
-Nonmutational epigenetic reprogramming
-Senescent cells
-Polymorphic microbiomes
One of the 6 original hallmarks of cancer is sustained proliferative signaling, which means that cancer cells stimulate their own ___, independent from normal signaling to achieve sustained proliferative signaling
Growth
Another one of the 6 original hallmarks is that cancer cells can evade growth suppressors, allowing them to avoid or overcome the signals that normally counteract and balance ____
Proliferation
Another of the 6 original Hallmarks is that cancer cells can resist cell ___
Death
The next of the original hallmarks of cancer is that cancer cells can induce angiogenesis to stimulate ___ ___ growth signaling
Blood vessel
Another of the 6 hallmarks of cancer is that cancer cells can activate invasion and metastasis to develop the ability to colonize ___ sites
Distant
The last of the 6 original hallmarks is that cancer cells can overcome the Hayflick limit and enable replicative immortality to achieve limitless ____ potential
Replicative
One emerging hallmark is that cancer cells can avoid ____ destriction
Immune
Another emerging hallmark is that cancer cells can de-regulate cellular ____ to support continuous cell growth and proliferation
Energetics
One enabling characteristic of cancer cells is that they have ___ instability and mutation, which causes them to generate random mutations including chromosomal rearrangements
Genome
Another enabling characteristic of cancer cells is that they benefit from the ___ ___ induced by immune cells in pre-malignant and malignant lesions, promoting tumor progression
Inflammatory state
Varmus and Bishop were the ones to find genes that allowed ____ (proto-oncogene–> oncogene)
Mutations
The purpose of cellular proliferation is growth maintenance and reproduction, but cancer cells multiply without a ___ ____
Controlled signal
Normal cells maintain homeostasis with ___ ___ ___, but cancer cells deregulate this mechanism and enable growth factors, primarily tyrosine kinase, to kind to the cell surface
Mitogenic growth signals
