2.1 Causes of Cancer

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Hello, my name is Kristianna Fredenburg and today I will speak to you about the causes of cancer.

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[image illustrating multiple causes of cancer, including environmental, behavioral, and genetic factors] As you saw in a previous video, cancer is caused by an uncontrolled division of cells which can be caused by several factors. Some of these factors are within our control, such as smoking or an unhealthy diet; while others are not, like some occupational exposures and our genetics.

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In this session, I will discuss a few of these factors in more detail and focus on some of the external causes and exposures associated with behaviors, as well as genetics.

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We are exposed to many external, or it can be also described as environmental, agents that are carcinogenic. The three major causes can be classified as chemical exposures, exposure to microorganisms, or radiation exposure. These external causes are responsible for many cancers, and this means that cancers and their development are, is preventable.

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[slide noting that Ramazzini’s observation occurred around 1700 in Italy; image of a historical illustration related to early observations of cancer in nuns] The association between cancer and the environment was first noted as far back as 1700 when Bernadino Ramazzini, known as the father of occupational medicine, observed a high rate of breast cancer among nuns.

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[slide noting that Pott’s observation occurred in 1775 in England; image of chimney sweeps, showing early occupational cancer risk] Several decades later, Percival Pott observed a high rate of scrotal skin cancer in men who formerly worked as chimney sweeps. Potts theorized that the chronic irritation from the soot on the young sweeps’ skin led to the skin cancer.

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[slide noting that Yamagiwa is the father of chemical carcinogenesis; image of Yamagiwa] It was not until 1915 that the link between the chemicals and cancer was proven. Dr Yamagiwa, a Japanese pathologist, painted coal tar, which has the same make-up as the soot the chimney sweeps were exposed to, onto the back of the skin of rabbit ears. After several months of treatment, skin cancer began to appear on the rabbits’ ear skin.

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[image illustrating tobacco use as a cause of different types of cancers throughout the body] Some of the same chemicals found in the soot and the painted the ears of Yamagiwa’s rabbits can be found in the #1 preventable cause of death—Tobacco. Tobacco use is one of the leading causes of cancer. 40% of all cancers diagnosed in the United States are linked to tobacco use. This includes smoking cigarettes, cigars, smokeless tobacco as well as exposure to secondhand smoke. Despite this well-known fact, 14% of adults in the United States are currently smokers.

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Infection through different microorganisms are also another cause of cancer. The main types of microorganisms associated are bacteria, viruses, and parasites. It is estimated that 17% of all new cancers worldwide are due to infections and can be mainly attributed to viral infections. A well-known cancer-causing virus is the human papillomavirus, or HPV. This virus has been associated with six different cancers, such as cervical cancer and head and neck cancer.

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[table listing infectious microorganisms linked to cancer, including associated cancers and dates of discovery] Here is a list of infectious microorganisms, with the date of discovery included, that have been found to cause various types of cancers. As you can see, HPV and its relationship to head and neck cancer is a fairly recent finding, identified in 2005. Other examples you may have heard about are hepatitis B and C, shown to cause liver cancer in 1995, or h. pylori, a bacteria that causes stomach cancer, discovered in 2000.

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The last environmental exposure I’m going to discuss is radiation exposure. Cancer caused by radiation comes from sources like the UV rays of sunlight.

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[image depicting a person receiving radiation therapy] High-energy sources of radiation from x-rays or from radiation treatments are also included in this. Vulnerable organs that are more susceptible to cancer after radiation exposure include bone marrow, thyroid gland, breast tissue, lung, and salivary gland tissue.

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Let’s now move to inherited cancers. Many people share a concern that if their parents had cancer, will they get it too?

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Less than 10% of cancer patients have inherited mutations in certain genes that can predispose them to cancer. A specific gene mutation can then predispose these individuals to cancers in multiple organs.

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[image of colon with numerous polyps characteristic of FAP] Let me provide an example. There is a disease of the colon called familial adenomatous polyposis syndrome – or FAP – and it is caused by an inherited gene mutation that causes abnormal growths in the colon called polyps. These polyps are located in the large intestine, which includes the colon and the rectum. The image you see is a cut open section of a colon showing hundreds of small polyps. When a person has this disease, hundreds, or even thousands, of small polyps can appear throughout the colon. If this condition isn’t treated, it is almost guaranteed that one of those polyps will become cancerous at some point in a person’s lifetime, typically by age 40. Because of this, it is common for those with FAP to have a total colectomy, or also known as the entire removal of the colon, in their late teens as a preventive measure.

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[diagram of APC gene function in regulating cell growth] The inherited mutation in FAP is in a gene called adenomatous polyposis coli gene- or APC for short. This cartoon helps to show what APC does in the normal cell and what happens in the cancer cell. In the normal cell, shown on the far-left, you can see that APC binds to the molecule beta-catenin. Beta-catenin is a molecule important for cell growth. When there’s no cell growth, APC binds beta-catenin and keeps it bound. In the normal cell when the cell wants to grow, APC releases the beta-catenin molecule, it then enters the nucleus, and the nucleus houses all of our DNA and genes, and beta-catenin can then trigger the cell to grow. In a cancerous cell, in FAP, APC is mutated and lost. Beta catenin can then enter the cell, the nucleus freely and cause abnormal cell growth or proliferation.

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When a person has this inherited mutation, APC, it is mutated in all their cells and they are then predisposed to malignant and benign tumors in other parts of the body. Such as liver cancer commonly found in children, brain tumors commonly found in children, and several types of benign tumors.

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[slide title: Other Inherited Predisposition] Here are some examples of cancers with their specific inherited mutations. Retinoblastoma (a tumor of the retina) has a mutation, an inherited mutation, in the RB gene. Melanoma (a type of skin cancer) has an inherited mutation in the p16INK4a gene. And breast and ovarian tumors can have an inherited mutation in BRCA1 and BRCA2 genes; you may have heard of those mutations.

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To summarize, cancer is commonly caused by external factors, which can be things like chemicals, microorganisms, or radiation. Most cancers are preventable, which is demonstrated in the example of tobacco use. Family genetics cause a small percentage of cancers, and changes in specific genes can predispose individuals to additional cancers. Thank you for watching.