Cancer Prevention: Risk Factors

• It is not possible at this time to guarantee that you will not get cancer.
• There are things you can do to reduce the chances of acquiring different types of cancer.
• Assessing personal risk factors is a large part of reducing cancer risk.

Risk Factors and Simple Prevention

• There are four different classes of risk factors: behavioral, biological, environmental, and genetic.
• Behavioral risk factors are behaviors that can be changed, such as smoking.
• Environmental risk factors are toxins in the surrounding environment that elevate cancer risk, including radon, air pollution, second-hand smoke, and asbestos.
• Biological risk factors are physical characteristics like gender, race, and age.
• Genetic risk factors are genes inherited from parents, like BRCA1 and BRCA2.
• All risk factors alter the DNA in our cells.
• DNA change, when not repaired, can lead to the mutations that cause cancer.
• Lifestyle changes are the easiest and cheapest way to stay healthy and reduce cancer risk.
• Avoid toxins, don’t smoke or drink large quantities of alcohol, and make healthy choices.
• Awareness of biologic and genetic risk factors and careful monitoring for signs of cancer can be enough.
• Knowing what cancers are in a family can help target cancer screenings and learn what warning signs to worry about.

Skin Cancer

• Skin cancer is caused by exposure to UV photons that damage the DNA in skin cells, UV rays have mutagenic properties
• The longer spent in the sun or in UV light, the more cells are at risk for changing.
• Prolonged exposure increases the risk of DNA mutations that result in cancer.
• After sun exposure, skin cells use repair processes and transcription factors like p53 to fix any damage that occurred.
• P53 produces proteins that stop the cell cycle, activates transcription of repair proteins, and induces apoptosis to truly damaged cells.
• More exposure means more mutation, and not all those changes can be corrected.
• If changes are drastic enough, and the damaged cells aren’t destroyed, cancer can be the result.
• Skin cancer is the most common type of cancer in the US, and its incidence continues to increase.
• Skin cancer can be prevented by wearing protective clothing and gear and using sunblock that protects against UVA and UVB rays.
• The ABCDE guide for skin cancer self-exams can be used to do a self-check for melanoma, the most dangerous type of skin cancer.
• A is for asymmetry.
• B is for irregular borders (not circular).
• C is for unusual color.
• D is for a diameter above 6 mm.
• E is for evolution, or change of the mole over time.

Cancer Screenings

• A cancer screening is a test performed to check for the presence of cancer.
• Screenings for females may involve pap smears and mammograms.
• Screenings for males involve prostate exams.
• Cancer screenings can detect cancer early so it can be treated; the earlier cancer is detected, the better the chances get for survival.

Normal Cells and Cancer Cells

• All healthy cells are regulated by the cell cycle.
• The cell cycle includes growth, performance of life-sustaining processes, division, and death.
• During growth, division, and scheduled death phases, checkpoint stations use enzymes, transcription factors, and other things to check the progress of the cell and ensure abnormalities haven’t developed.
• Checkpoints ensure that only healthy, normal cells are allowed to progress and divide.
• Damage to the cell can damage checkpoints, which can cause abnormal cells to grow and proliferate without correction or apoptosis.
• Abnormal cells are cancer.
• Chemicals, UV, and age can cause changes at the DNA (gene) level, or people can be born with the wrong genes.
• Tumor suppressor genes suppress cancer, working inside cells to stop the growth and division of abnormal cells.
• If tumor suppressor genes become abnormal, they work to correct the problem or trigger apoptosis (cell death).
• Cells will kill themselves for the good of the body, but sometimes these signals get ignored because of something else going wrong in the cell.
• Transcription factor p53 is another protective force in cells.
• Proto-oncogenes are a group of genes that cause normal cells to become cancerous when they are mutated.
• The mutated version of a proto-oncogene is called an oncogene.
• Proto-oncogenes encode proteins that stimulate cell division, inhibit cell differentiation, and halt cell death.
• Oncogenes typically exhibit increased production of these proteins, leading to increased cell division, decreased cell differentiation, and inhibition of cell death.
• Proto-oncogenes can become mutated, becoming oncogenes that make cells cancerous.
• If that happens, tumor suppressor genes may not be able to do their jobs properly and cancer can develop.
• Breast cancer can develop because of gene abnormalities.
• BRCA1 and BRCA2 are genes active in breast cells that act as proto-oncogenes.
• The normal version of the allele acts as a tumor suppressor gene.
• In some people, this gene has mutated into an oncogene that may cause cancer, increasing their chances of getting cancer.
• For a normal woman, the chances of breast cancer are 10%, while in someone with a BRCA mutation, the risk increases to about 80%.
• Several tests can identify this gene mutation, including DNA sequencing and marker analysis.

Marker Analysis

• BRCA1 and BRCA2 are two genes commonly found in people who develop hereditary cancer.
• In a healthy individual, these two genes are tumor suppressor genes.
• In someone with a mutation, these genes don’t do their job and tumors are more likely to develop, drastically increasing the chances of developing breast cancer.
• The presence of the mutated form of either gene results in a greater risk of breast cancer.
• The BRCA2 gene is accompanied by a section of DNA consisting of a series of short tandem repeats, or STRs.
• These small chunks of DNA have a repeating pattern that repeats a variable number of times right next to the BRCA2 gene.
• Variations in the number of STRs creates different versions of the BRCA allele, most of which code for the normal proto-oncogene that helps protect from cancer.
• Some versions of the allele, however, are mutated, are not protective, and increase the risk of cancer.
• By detecting the “bad” allele versions (the BRCA2 mutation) people can determine whether they need to take extra precautions.
• It is currently possible to complete a test called marker analysis to find out your chances of developing certain types of cancer, like breast cancer.
• Marker analysis is a technique where the gene mutation is analyzed using a genetic marker instead of directly analyzing the gene itself.
• If a family member is known to have a BRCA2 mutation, it is possible to compare the alleles between members.
• STRs occur in gene introns (non-coding regions of DNA), so the variation in the number of repeats does not usually affect gene function, but STRs can be used to differentiate between different alleles.
• Because pieces of DNA that are near each other on a chromosome tend to be inherited together, an STR that is located on chromosome 13 next to the known BRCA2 mutation can be used as the genetic marker for this case.

Steps to Identify Alleles

• Start with the well called DNA Markers.
• Markers are DNA fragments of known sizes.
• Identify each band and calculate its Rf value by getting two numbers:
  • A) the distance between the bottom of the first well and the bottom of the “reference line” (in millimeters)
  • B) measuring the distance between the bottom of the first well and the bottom of each band (in millimeters)
• For each band, divide B/A to calculate the Rf values for each band.
• On log paper, plot those values with Rf value on the X axis and fragment length on the Y axis.
• Create a line of best fit by drawing a line in the place that best touches or comes close to as many of your plotted points as possible
• For each remaining well, measure the distance between the bottom of the well and the bottom of each band; calculate their Rf values.
• Use these values to locate the fragment lengths on the graph you have created; this tells you the fragment size of each band.
• Identify alleles that are normal and abnormal using a results table that will tell you which allele versions individuals have, as well as which are causing the mutations.

Cancer and Viruses

• Avoiding the viral infections that lead to certain cancers is another way to prevent getting those cancers.
• Cervical cancer is more than 80% caused by an infection with the HPV virus, which is transmitted from males to females during intercourse.
• Certain types of liver cancer and Hepatitis are linked to the HBV and HCV viruses.
• The EBV/Epstein Barr/Mono/Kissing Disease virus has been linked to several forms of cancer.
• Vaccination can prevent these types of cancers.
• If an individual is immune to specific cancer-causing viruses, they can not infect the individual, mutate the DNA, and cause cancer.
• Vaccines like the Hepatitis B, C and Gardasil exist for this reason.
• Virologists can identify cancer-causing viruses and develop vaccinations that will reduce those infections.
• Virologists are working to cure cancer.

Routine Cancer Screenings

• Information on routine cancer screenings and their importance.
• A timeline for cancer screenings needed in your lifetime.
• Includes screenings shared between men and women, such as lung cancer screening, colorectal cancer screening, and skin cancer screening.