Oncology 305 Exam 2

Epidemiology?

The branch of medicine which deals with the incidence, distribution, and possible control of diseases and other factors relating to health.

What do epidemiologists study?

Where should government spend money?
 Where should medical providers focus efforts?
 Where should researchers invest time/energy?
 Which groups of people should be concerned about cancer?

Retrospective studies?

Study performed using information/events taken place in the past.

Prospective studies?

Study generates new data

What do descriptive studies look at?

Summarize disease patterns or distributions
• Sex
• Race/Ethnicity
• Age
• Location
• Time
• Etc.
 Potentially identify risk factors (do certain sub-pops differ
from mean)
 Where should government spend money?

Incidence?

Number of new cases that develop in a specified time period

Prevalence?

Number of total cases in a specified time period

Mortality?

Number of deaths in a specified time period

Units?

Per person

What is the most prominent cancer in males worldwide?

Prostate cancer

What is the most deadly cancer for males worldwide?

Lung cancer

What is the most prominent cancer for females worldwide?

Breast cancer

What cancer causes the most deaths worldwide for females?

Breast cancer

What is an important risk factor in looking at cancer statistics?

Age

Cancer is the second most common cause of death among children ages..

1-14, the first is accidents

Since 1970 cancer rates have declined by what percent?

Cancer death rates in children have declined by 71% since 1970

What is the most common childhood cancer?

Leukemia

Death rates for leukemia from 1970 till now have declined by what percent?

84%

Descriptive studies?

Are there particular subpopulations that have higher rates of cancer?

Case-control studies?

Compare people that have cancer to those that don’t have cancer and see how they differ.

Cohort studies?

Separate groups based on an exposure and then see which one has a higher risk

Observational studies?

No intervention/ treatment is given

Studies of risk-modifying factors on health or other outcomes based on populations
defined either geographically and/or temporally

Low cost/ easy

Can only generate hypothesis

Describe a case control study

Retrospective observational study comparing two groups (cases vs. controls)
 Cases recruited at initial diagnosis
 Controls should be picked from same general population, ideally as similar to
the cases as possible, and without any consideration to the risk factor of
interest
• Control group is usually bigger than case group
 Prone to recall bias as risk factors are evaluated retrospectively
 Cheaper and quicker to complete than cohort studies

Describe cohort study

Prospective observational study
 Intended risk factor is measured throughout and before study
 Best for common outcomes, requires large numbers, takes a long time to
complete
 Expensive!

Describe interventional studies

Experimental rather than observational
 Cohort Study where intervention replaces “risk” factor
• Drug vs Placebo
• New approach vs Standard of Care
• Commonly double-blinded and randomized
 Ethical challenges
• Only positive interventions
• Placebo or other negative controls

Association studies?

Statistical dependence of two variables to each other
• Information about variable X lets you predict the behavior of variable Y
• But the reverse is also true!!

Correlation studies?

monotonic (linear) relationship between variables
• Special case of association

Causation studies?

X is responsible for Y
• Need to make sure we eliminate coincidences/confounds
• Prospective studies are better for this than retrospective studies

Strength?

Stronger associations are more likely to be causal than weaker associations

Consistency?

Has this been reproduced by multiple groups under different circumstances (prospective and retrospective)

Specificity?

Single cause to single effect

Temporality?

Cause must precede the effect

Biological gradient?

Clear (monotonic) dose-response curve

Plausibility?

Is there prior biological (mechanistic) data that can explain the causal relationship?

Coherance?

The cause-effect relationship should not contradict what we know about the disease.

Experimental evidence?

Result from intervention studies or pre-clinical studies confirm the observational studies

Analogy?

Have we seen similar effects with exposures of the same class? Similar things have similar effects.

Carcinogenesis?

Process of transformation from normal cells to cancer cells

Epidemilogical studies can identify..

Cancer risk factors

Genetic factors include?

Genetic syndromes, single nucleotide polymorphism

Behavioral factors?

Nutrition, lifestyle factors

Environmental factors?

Regions of living, air quality, water quality, ect…

Carcinogenesis/ tumorogenesis?

Process of transformation from normal to cancerous

Prevention is more… effective than treatment?

Cost

Most cancers devlop over…

Decades of time

Duration of exposure determines…

Determines the onset of detectable disease

Dependent incidence rates

Differ dramatically from typical adult cancers, suggesting factors other than increasing age must be invoked to understand mechanisms of tumorgenesis.

“Hallmarks of cancer”

Alterations in multiple pathways needed

“Multi-step tumorgenesis”

Over time, normal cells evolve into cells with increasingly neoplastic phenotypes

Cell component that is not recycled

DNA

DNA guides…

The production of other components of the cell

Mutation?

Permanent change to DNA

Mutagenesis?

the process by which the genetic information of an organism is changed, creating mutation

Mutagenesis can be the result of…

DNA damage or it can occur spontaneously

Around how many DNA damages occur each day?

60,000

Mutagenesis is sometimes necessary for…

Evolution

Human DNA error rate is?

1 mistake per 100 million (10^-8) to 1 billion (10^-9) nucleotides

What type of cancer usually has a higher error rate?

Hereditary cancers

Nucleotides per cell?

3 billion

Around 3 mutations per cell division on average

No exposure to a carcinogen?

Even if there is no exposure to a carcinogen, DNA replication alone is capable (though unlikely) to generate the changes needed to develop cancer.

Is a single mutation enough to cause a cancer?

Most likely not

Tumor accumulate genetic and epigenetic alterations?

As tumor progression proceeds

In humans tumorgenesis had been studied the most for what cancer?

Colon cancer

The number of inactivated tumor suppressors… the number of activated oncogenes in human cancer cell genome

Greatly exceeds

APC is found to be inactivated in…of colon carcinomas (tumor suppressor)

80%

Initiator

Mutagen

Promoter

non-mutagenic

What are the two categories of carcinogens?

Category 1: Initiator

•Most known carcinogens (particularly at small doses)

•Mutagens (DNA damage)

Category 2: Promoter

•Induce cell proliferation, inflammation, and/or prevent cell apoptosis

•Cannot induce cancer unless initiation has already occurred

Promoters promote…

Expansion of initiated tumor clones

•For an initiated cells to acquire a second mutation its clonal descendants must become so numerous that a second, low probability mutational event is likely

Theory of tumor promotion?

The critical determinant in the rate of tumor progression in many human tissues

Steps of mutagenesis?

Mutagens initiate transformation from normal to cancer

•1^st hit

Promoters repeatedly stimulate the initiated cell to divide

•Errors in DNA replication and effects of the 1^st hit lead to 2^nd hit, and so on

Eventually, DNA of the cell becomes unstable (genomic instability)

•Accumulation of new hits accelerates

•New hits lead to conversion from benign to malignant

Because of this instability the mutation profile of the tumor become heterogeneous. New cells keep gaining newer mutations

Stem cells?

Stem cells have ability to replicate indefinitely

A single stem cell does not need to proliferate frequently

Bulk of tissue proliferation occurs in the progenitor cells

This stem cell hierarchy also appears to operate in many cancers

Stem cells are resistant to…

Conventional cancer therapies

Chemical carcinogen?

Any discrete chemical compound which has been shown to cause cancer in human or animal studies.

Animal studies?

Directly induce cancer in test animals using a large sample of animals, usually of two or more species with varying dose and time parameters. 

Epidemiological studies?

Determine the relationship between a cancer suspect chemical and a human population over a long period of time.

Molecular dosimetry?

Carcinogen-macromolecule adducts

Cytogenic end points

Mutational spectra and frequency

Inherited cancer predisposition

Genetic polymorphisms of carcinogenic metabolizing enzymes

Obesity increases the risk of…

Of cancer of the: esophagus, pancreas, colon and rectum, breast (after menopause), endometrium (lining of the uterus), kidney, thyroid, and gallbladder

Processed meats have been identified as…

Classified as category 1, with red meat classified as category 2A (with links to colorectal cancer)

Exposure is unlikley to be…

Homogenous

How many known carcinogens are there in cigarette smoke?

60

Is nicotine a carcinogen?

No

E-cigarette liquid is a combination of…

Propylene glycol, glycerin, nicotine and flavorings

Marijuana smoke has around… different carcinogens?

33

Health disparity?

The disproportionate burden of disease, disability, or premature death borne by specific population groups

Population groups may be defined by…

By demographic measures of geography, gender, age, sexual orientation, socio-economic status, race/ethnicity

Factors that impact health

Genetics – we have already covered some of this

Lifestyle factors – diet, exercise, tobacco use, etc.

Environmental Exposures

Socioeconomical Factors

•Health Resource Availability

•Health Access Risk Factors

•Can also influence environmental risk factors

Different communities are exposed to different…

Levels/ carcinogens

ex. Air pollution, radon gas, chemical spills

Socioeconomic factors?

Education

Occupation and Employment

Income and Poverty

Environmental and Neighborhood Segregation

Racism and Discrimination

Access to care (health insurance, language, etc)

Health resource avaliibility

Access to Healthcare Services

Differential health care access may lead to disparities in health care quality

Minorities and the poor receive lower quality health care and have worse  access to care

Rural communities usually do not have specialist care and patients must travel farther to receive appropriate care

Healthcare access risk factors?

Language

Lack of Health Insurance

Quality of Health Insurance

Cultural Competency

Disparities in Ability to pay

Lack of trust in health care leading to reduced transparency

Disparities in the cancer continum

•Incidence

•Participation in early screening programs

•Stage at diagnosis

•Therapy

Survival

Which race of males have a higher incidence rate?

African American males

What females have a higher cancer incidence?

White females

Which race/ gender has a higher mortality rate from cancer?

African American males and females

Define inflammation

Mechanism of innate immunity, where immune cells are recruited to a site of tissue injury, infection, irritation etc.

•Classically involves heat, pain, redness and swelling

Acute inflammation starts the..

Start of an immune response