Cancer Part 3

Welcome back to our third (and final) cancer introductory post. As you’ve probably learned, cancer is a very common, yet complex disease, which is one of the reasons we have devoted three introductory posts to the topic. Up to this point we’ve learned some vocabulary, separated facts from fiction, learned about preventative measures as well as different cancer treatments and introduced the two main drivers of cancer progression- oncogenes and tumor suppressors. In today’s post, we are going to tie up some loose ends by touching on environmentally induced cancer vs. hereditary cancer, and finally we will review the hallmarks of cancer, or the traits that most cancers share.

undefinedCigarette smoke causes cancer.

undefinedTanning beds cause cancer.

The majority of people “know” these things cause cancer because we’ve heard these statements hundreds of times. But do you know how or why these factors cause cancer? Cigarette smoke and UV radiation (tanning beds) are considered carcinogens, or cancer causing agents. Most human cancers (nearly 90%) are caused by exposure to chemical or physical carcinogens. Carcinogens drive cancer progression by causing DNA damage resulting in mutations or DNA strand breaks which lead to gene amplifications and rearrangements. Imagine cutting two strings and having to remember the exact order they were in. This is what the cells face when there is a double strand DNA break. These mutations typically occur in proto-oncogenes or tumor suppressor genes. The fate of carcinogen initiated cells is strongly influenced by exposure to agents that can promote or prevent their survival and expansion. Chronic exposure to carcinogenic agents drives cancer progression, which takes place over decades in humans, one of the reasons that cancer risk increases with age. 

Cigarette smoke and UV light are just two examples of the numerous cancer causing agents within our daily environments. These environmentally induced cancer causing agents can be grouped into three different classes

Chemical carcinogens

There are MULTIPLE chemicals in cigarettes that are carcinogenic.
The burning of fossil fuels release carcinogenic chemicals (polycyclic aromatic hydrocarbons)
Aromatic amines (dye industry)
Certain plant toxins (aflatoxin)

Physical Carcinogens

Ionizing radiation (X-rays, gamma rays, etc.) 
Everyone is exposed to low dose radiation EVERYDAY
—Sources include outer space, the sun, building materials, the ground- there’s no way to avoid this
There is no evidence that microwaves/ cell phones induce cancer
UV radiation  
—TANNING BEDS ARE DAMAGING. Not wearing sunscreen is DAMAGING!
——Spray tans are harmless!

Biological Carcinogens

Retroviruses
—Viruses that squeeze themselves into the human genome
—Typically the integration of these viruses results in the inability to control cell growth (aka- gas pedal is to the floor)
DNA viruses 
—HPV (human papillomavirus, transmitted via sexual intercourse) is a cancer causing DNA virus
——Gardasil vaccine protects against contracting the HPV virus and has significantly decreased the instances of cervical cancer

All three classes of carcinogens share some similarities, listed below:

-All carcinogens ultimately damage DNA. 
-Carcinogens can be metabolized (broken down within the body) and then form strongly reactive intermediates. In these instances, the intermediates may be what damages the DNA. 
-DNA damaging properties have been conclusively linked to cancer initiation and progression. 
-Mechanisms of DNA damage repair play an important role in carcinogenesis 
-When a carcinogen induces full blown cancer, it is referred to as a complete carcinogen. However, a single carcinogen does not always cause cancer alone, rather the carcinogen acts as a building block and other changes must also occur to cause cancer. This is a very complex topic so we won’t go into more detail, but don’t hesitate to ask us questions if you’re interested! 

While nearly 90% of cancers are environmentally induced due to some type of carcinogen or combination or carcinogens/ other factors, the other 10% of cancers are hereditary, meaning an individual inherits the cancer causing gene/ mutation from one or both parent(s). 

Some commonalities of genetically induced cancers are:

-The cancer is normally observed in two or more close relatives (on the same side of the family).
-Individuals are of early age at diagnosis.
—Remember that normally, cancer is more commonly seen in older individuals. Being diagnosed at an earlier age is sometimes indicative of a genetic disease. 
-Multiple primary tumors are observed in the same individual.
—These tumors are often bilateral (found in both breasts).
-Constellation of tumors consistent with specific cancer syndrome (e.g., breast and ovary)
-Evidence of autosomal dominant transmission (meaning one copy is enough to cause a phenotype –  Check out the Genes post for a refresher)
—Multiple affected generations 

One of the most infamous hereditary cancers is breast cancer, specifically BRCA (BReast CAncer gene) caused breast cancer. BRCA is a gene that is known to mutate and cause breast and/or ovarian cancer in a family. Another common hereditary cancer is retinoblastoma. Retinoblastoma is a rare form of cancer that develops in the eye and is caused by inherited mutations in the RB gene, which is a tumor suppressor classified as a “gatekeeper”. 

While some families are predisposed to cancer due to genetics, most cancers are not inherited. If your family does exhibit some of the aforementioned characteristics of genetic cancers, there are ways to test whether or not you carry the proto-oncogene or genetic mutation that causes the disease. If you’ve ever watched Keeping up with the Kardashians, you might remember when Kris Jenner urged all of her daughters to get the genetic test to determine whether they had the genetic predisposition for developing breast cancer due to their grandmother’s bout with breast cancer. Normally, by catching cancer in the early stages or learning of a genetic predisposition, you are setting yourself up for a better chance at surviving or “beating” cancer. 

Finally, as a summary to all of our cancer introductory posts, we are going to quickly review the Hallmarks of Cancer, or the traits that most cancers share. In 2000, Hanahan and Weinberg proposed six characteristics (or rules) that are programmed into normal cells and breached by cancer cells. However, over the past two decades as cancer research and understanding has increased, there are four newer hallmarks.

The 6 Original Hallmarks of Cancer

  1. Sustaining proliferative signals
    • The gas pedal is to the floor, the cells will grow indefinitely
  2. Evasion of growth suppressors
    • The brakes aren’t able to slow down the cell(s) from growing/ surviving
  3. Resisting cell death
    • The cell is able to avoid the normal factors within the body that would kill a dysregulated cell  
  4. Replicative immortality
    • Infinite generations of descendants/ infinite reproduction
  5. Angiogenesis
    • The cells are capable of maintaining their own blood (nutrient) supply
  6. Invasion and metastasis
    • migrate/ spread to other parts of the body

Hallmarks of Cancer: The Next Generation (4 new hallmarks)

  1. Tumor promoting inflammation
    • Chronic/ long lasting inflammation can lead to angiogenesis (see above) and increase the chances of metastasis
  2. Genomic instability and mutations
    • Cancer cells begin from small mutations but normally progress to have genomic instability/ chromosomal abnormalities
  3. Avoidance of immune destruction
    • Avoids the “police”
  4. Dysregulated cellular energetics
    • Dysregulated metabolism- inhibition of mitochondrial ability to control aerobic respiration

As we wrap up our cancer introductory posts, we hope you have learned about some of the science behind cancer progression. Cancer research consumes BILLIONS of dollars every year and yet, we are so far from understanding all of the mechanisms associated with different cancers, much less how to best treat all the different types of cancer. Next week, we will discuss a specific type of cancer treatment called immunotherapy, which manipulates your body’s immune system to treat cancer. In the meantime, let us know if you have any questions, comments or feedback and don’t forget to follow/ like us!

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Written by Megan
Illustrated by Rhea

Disclaimer: We are not medical professionals and the above information is not meant to serve as diagnostic factors or medical advice. Further, the opinions in this post are our opinions and in no way reflect the opinions of our mentors or the Medical University of South Carolina.

Resources & Recommended Reading

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646‐674. doi:10.1016/j.cell.2011.02.013
Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57‐70. doi:10.1016/s0092-8674(00)81683-9
https://www.cancer.gov/about-cancer/causes-prevention/genetics
https://www.cancer.org/cancer/cancer-causes/general-info/known-and-probable-human-carcinogens.html
https://www.cancer.gov/about-cancer/causes-prevention/risk/substances/carcinogens

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