• TRUE: Compared to other major diseases, cancer death rates have changed little
over the past 60 years.
• TRUE: More and more people are getting cancer because we live longer now and
cancer increases with age.
• TRUE: Cancer is a global problem.
o More than 60% of the world’s new cancer cases occur in Africa, Asia, and
Central/South America
• TRUE: In 2003, despite increasing population size and lifespan, the American
Cancer Society announced the of deaths from cancer in the U.S. total number
• TRUE: Recent statistics show decreases in for some cancers (lung, mortality rates
breast, colon, prostate)
• TRUE: Cancer death rates have fallen 25% since 1991.
• TRUE: A single nucleotide polymorphism (SNP) is found in more than 1% of the
population, while a mutation is found in less than 1% of the population
• TRUE: Mutations can be repaired or cells can be prevented from mutating from
replicating by mutation control.
• TRUE: Mutations happen in human cells but are normally repaired or all the time
eliminated to maintain order and stability within the organism.
• TRUE: There are multiple highly evolved cellular mechanisms that exist to protect
against changes in DNA (mutations) that occur as part of life.
• TRUE: In normal cells, if DNA damage can’t be repaired, programmed death of
cells or immune destruction of cells occurs.
• TRUE: The development of cancer requires the loss, malfunction, or overriding of
normal mutation control mechanisms.
• TRUE: The loss of control seen in cancer cells is itself caused by mutation in control
mechanisms.
• TRUE: All processes involved in the development of cancer are integrally linked to
fundamental mammalian biology and the evolution of biological life itself.
• TRUE: Elimination of cancer would require elimination of mutation.
• TRUE: Mutation is integral to normal biology and cannot be eliminated.
• TRUE: Cancer can never be eliminated as a disease process.
• TRUE: We are evolved to be susceptible to cancer.
• TRUE: Genomic “instability” is fundamental to cancer’s ability to acquire new traits
and pass them on to progeny
• TRUE: Genomic instability leads to accumulation of key (“driver”) mutations
required for cancer progression.
• TRUE: Genes that drive cell division are always “on” or gain function.
• TRUE: Not all tumors are cancer but all tumors are abnormal and require diagnosis
• TRUE: Most cancers come from dysplasias, not benign neoplasms
• TRUE: Dysplastic cells typically grow in masses and form benign tumors
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• TRUE: Expansion of dysplastic cells occurs within flat surface, has ill-defined
borders, and cannot be identified with the naked eye
• TRUE: Biopsies and cytology with microscopic examination is required for diagnosis
• TRUE: Carcinoma is by far the most common human malignancy
• TRUE: Carcinoma in situ never metastasizes
• TRUE: Not all carcinogens are mutagens, but all mutagens are carcinogens
• TRUE: Most cancer-initiating mutations are acquired, not inherited
• TRUE: Somatic mutations cannot be inherited, while germline mutations can be
inherited.
• TRUE: Cancer is primarily an environmental disease.
• TRUE: Laboratory studies in humans that are analogous to those in non-human
systems are unethical.
• FALSE: Some carcinogens have been found to always cause cancer, under all
circumstances.
• TRUE: There are some substances in vegetables and fruits that may help protect
against cancer, especially in cruciferous vegetables!
• TRUE: Viruses associated with human cancers include: Hep B/C and HIV.
• TRUE: Most cancer can be prevented through behavior change.
• TRUE: A causal factor is a determining element of a disease.
• TRUE: Detection by screening decreases the time to diagnosis and treatment.
• TRUE: Sensitivity does not take false positives into account and specificity does not
take false negatives into account.
• TRUE: All causal factors are risk factors for cancer, but not all risk factors are
causal
• TRUE: Cancers generally take years to develop following carcinogen exposure.
• TRUE: Some of the agents that are used to treat cancer also cause cancer.
• TRUE: The right therapy and management are dependent on the right diagnosis
and assessment.
• TRUE: For most cancers, there are no effective screening tests.
• TRUE: The rarer the disease, the more likely false positives are to be.
• TRUE: Our most effective screening tools are the Pap smear and colonoscopy
• TRUE: PSA-based screening is Grade D, meaning it is highly discouraged.
• TRUE: Physician education is highly necessary because the large number of
uninformed patients is related to the large number of uniformed clinicians.
• TRUE: Mortality rates are the only way to judge cancer screening accurately.
• TRUE: The two types of bias that mislead physicians into thinking screening saves
lives are lead time bias and over-diagnosis bias
• TRUE: The goal of screening is to detect disease early and treat before cancer has
progressed.
• TRUE: Effective screening is defined by a decrease mortality from the disease in
the screened versus unscreened population
• TRUE: The benefit-to-harm ratio of screening tests depends on false negative and
false positive rates.
• TRUE: The predictive value of a screening test depends on the prevalence of the
disease.
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• TRUE: Cancer site implies survival differences.
• TRUE: The less resemblance to normal morphology, the higher the grade.
• TRUE: High grade tumors grow and spread more aggressively and are less
responsive to therapy than low grade tumors.
• TRUE: Grade of cancer is based on degree of differentiation of cancer cells.
• TRUE: Stage of cancer is based on how far cancer has progressed at diagnosis
based on extent of local tumor and spread of disease (TNM system)
• TRUE: The greater the spread, the higher the stage.
• TRUE: Survival correlates with stage (highest stage being incurable)
• TRUE: Stage is a more powerful predictor of outcome than grade and is more
clinically useful in classifying patients.
• TRUE: The higher the tumor grade and stage, the lower the probability of survival
• The mortality rate is the cancer deaths per 100,000 population per year
• The biggest factor in improved prevention, detection, and treatment is the decline in
smoking
• Natural evolution is the mutation and selection that favors “fitness” with respect to
competition, adaptation, and survival within a physical environment
• Cancer evolution is the mutation and selection that favors “fitness” with respect to
competition, adaptation, and survival within the body’s biological environment
• A permanent change in the nucleotide sequence of DNA that can be passed on to
daughter cells with mitosis is called a mutation
• A specific type of mutation that is considered to be in the realm of normal human
variation is a single nucleotide polymorphism
• A SNP is defined by convention according to frequency
• The acquired characteristics cancers have in common include:
o Uncontrolled cell division
o Invasion and destruction of normal tissues
o Metastasize: Ability to travel to and colonize other parts of the body
• Hallmarks of cancer include abnormal form and function.
• Some examples of abnormal form include: abnormal cytology and abnormal
tissue (histopathological) morphology
• Some examples of abnormal function include:
o Resistance to cell death
o Sustaining of proliferative signaling
o Evasion of growth suppression
o Limitless replicative potential
o Ability to invade and metastasize
o Induction of new blood supply (angiogenesis)
• “Cancer” is the term that refers to a group of diseases in which cells: abnormal
o Divide without control
o Invade (and destroy) other tissues without control
o Metastasize (travel to other parts of the body through the blood and lymph)
• The process of a normal cell turning cancerous is called carcinogenesis
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• Carcinogenesis always requires in the genome of the cell ( ) mutation initiation
AND proliferation (growth) of the genetically altered cell (promotion)
• Additional mutations accumulate in a multistep process with growth over time
( )progression
• A mass of abnormal (mutated) cells is called a neoplasm
• Normal cell growth includes (increase in cell size) and hypertrophy hyperplasia
(increase in cell number), while abnormal cell growth includes dysplasia (pre-
cancer; does not form mass/tumor) and (benign or malignant) neoplasia
• Dysplasia and neoplasia are irreversible
• Initiators cause mutation in one cell capable of dividing
• Promoters promote clonal expansion (proliferation) of initiated (mutated) cells, but
don’t affect normal cells
• Progressors cause additional mutations that confer additional growth-aggressive
changes
• Low grade dysplasia occurs when initiated cell clones gain additional proliferative
advantage and begin to change their morphology
• High grade dysplasia (carcinoma in situ) occurs when more mutations happen
within proliferative cell line lead to development of pre-invasive cancer; it is high risk
for progression to cancer and be treated!!must
• Invasive carcinoma (malignant neoplasm) invades through basal lamina is now
classified as malignant and considered capable of metastasis. This is the beginning
of epithelial-mesenchymal transformation
• Cancer cells with migratory and invasive properties break through walls of
lymphatics or blood vessels in metastasis
• Carcinoma is cancer arising from epithelial cells (covering/lining cells)
• Keratin “pearl” is a concentric collection of cornified squamous cells seen in
carcinoma
• Sarcoma is cancer arising from connective tissue cells
• Lymphoma is cancer that arises from immune system cell precursors in bone
marrow or lymph nodes
• Systemic Leukemia arises from blood forming cells in bone marrow
• Melanoma arise from pigment-producing cells in epithelia
• Acute lymphocytic leukemia happens when leukemic cells have replaced normal
blood forming cells
• Anaplastic refers to cancers that are unclassifiable because they are so
undifferentiated
• Neoplasias are abnormal tissue growths characterized by mutation, abnormal cell
appearance, abnormal tissue architecture, and growth advantage
• Neoplasms are classified by their site of origin and their predominant cell type
(differentiation pattern)
• Carcinogens are agents that cause cancer
• Mutagens are agents that alter DNA
• Empirical science includes information gained by experience, observation, or
experiment observation, induction, deduction, testing
• Causal factors are those that are mutation-causing risk factors
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• Causal inference is the process of deriving cause-and-effect conclusions by
reasoning from knowledge and factual evidence reduction in risk with removal of
exposure, consistency of association, biological plausibility
• Risk factors are characteristics, conditions, or behaviors that increase probability of
a cancer; vary in degree of risk imposed and may/may not be a causal factor
o Some can be treated: chronic inflammation, viral infections, bacterial
infections, diabetes, etc
o Tobacco and diet/obesity are biggest causes of cancer
• Obesity is associated with substantial metabolic and endocrine abnormalities and
has been linked to 13 different cancers
• Screening for cancer involves testing people and testing without symptoms
defined populations at risk (usually those )
• A test’s ability to correctly identify those WITH the disease is test sensitivity
• A test’s ability to correctly identify those WITHOUT the disease is test specificity
• Test performance is depicted by the RoC curve, where the area under curve (AUC)
represents perfection, measuring the diagnostic accuracy across spectrum of test
values
• The probability that an individual is affected by the disease when the test result is
positive (counting false positives) is the positive predictive value
o =
• The probability that an individual is not affected by the disease when the test result
is negative (counting false negative) is the negative predictive value
o =
• Diagnosis is the identification of a disease in an individual through process of
evaluation and elimination
• Symptoms signs include patient’s perceptions, while are examiner’s observations
• TNM Staging System refers to tumor, nodes, and metastases progression.
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• Imhotep: documents first reported case of cancer
• Hippocrates: uses word carcinoma to describe tumors and recognizes benign
versus malignant
• Galen: Uses word “oncos” meaning “mass” to describe tumors
• Celsus: translates word crab into Latin as “cancer”
• Sir Percivall Pott: first demonstrated cancer can be caused by environment
• Rudolf Virchow: discovered cancer is made up of otherwise normal cells
• Theodor Boveri: suggested that cancer comes from single somatic cell with
chromosomal alterations causing uncontrolled growth
• Thomas Hunt Morgan: demonstrated genes are carried on chromosomes,
validating Boveri’s hypothesis
• Paul Ehrlich: coined term “chemotherapy” and developed concept of using
chemicals to treat disease
• Sir Austin B. Hill and Sir Richard Doll: Linked smoking and lung cancer
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• William S. Halsted: Developed “radical mastectomy” procedure with the notion
that the wider the excision, the greater the chance of preventing metastasis and
curing disease
• Claudius Regaud: Showed normal tissue sparing effects by reducing dose rates
and delivering doses at spaced intervals could stop rapidly growing cells like cancer
• George Papanicolaou: Developed Pap test for early detection of cervical cancer
• Sidney Farber: Achieved first remission of cancer using drugs; father of
chemotherapy
• Peter Nowell and David Hungerford: reported recurrent chromosomal
translocation (Philadelphia chromosome in CML cells)
• Henry S. Kaplan: established importance of clinical staging and used radiation
therapy to successfully treat Hodgkin’s disease
• Vincent T. Devita: developed first combination therapy to produce a high
proportion of complete remission and cure (MOPP)
• Bernard Fisher: lumpectomy just as effective as radical mastectomy for breast
cancer
• Harald Zur Hauzen: Discovered causal link between HPV (Human Papilloma
Virus) and cervical cancer, leading to development of a vaccine
• Michael Bishop and Harold Varmus: discovered viral genes with ability to cause
cancer are derived from mammalian genome (cancer causation is innate)
• Weinberg, Wigler, and Barbacid: simultaneously discovered first human
oncogene (RAS)
• Webster Cavenee: first validation of presence of tumor suppressor gene in
humans
• Brian Druker: discovered CML is caused by a single driver mutation and its
oncoprotein; able to provide a cure to formerly incurable disease
• Dennis Slamon: identified amplified oncogene in breast cancer
• Gordon Freeman: discover PD-L1 is expressed by cancer cells, allowing them to
evade immune destruction
#$% &'$
• National Cancer Institute: Federal government’s primary agency for cancer
research and training
• National Cancer Act: Amended Public Health Service Act to strength NCI
• The Cancer Genome Atlas: Goal to define and catalog all genomic defects in
cancers
• International Agency for Research on Cancer: evaluates risk of carcinogenicity
with Group 1 being worst and Group 4 being decent (lists those found to be not
carcinogens)
• The Report on Carcinogens (RoC) lists two groups, those known to be human
carcinogens and those reasonably anticipated to be human carcinogens
• U.S. Preventative Services Task Force gives evaluations and recommendations
(grades) regarding cancer treatments and practices
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