How Do We Know What Causes Cancer?

Determining whether something can cause cancer takes time and careful research. Scientists study results from lab tests and look for patterns in groups of people. Expert agencies then use this evidence to classify how strongly a substance is linked to cancer.

What is a carcinogen?

A carcinogen is something that can cause cancer. Carcinogens can be chemicals, infections, some kinds of radiation, smoke and air pollution, or other substances.

To be called a carcinogen, a substance must first be studied extensively. Then, 1 or more agencies must evaluate the scientific evidence and determine it to be a cause of cancer.

How do carcinogens cause cancer?

Cancer develops when changes (mutations) in certain genes lead to abnormal cell growth. Some gene changes linked to cancer are inherited from a parent, but most are acquired during a person’s life. Many times, gene changes can be caused by the effects of certain lifestyle behaviors or exposures in the environment.

Not all carcinogens work the same way:

• Some cause cancer by directly causing gene changes.
• Others do not affect genes directly, but can lead to cancer in other ways. For example, they may cause cells to divide at a faster than normal rate, which could increase the chances that abnormal gene changes occur at some point.

Are all carcinogens equally harmful?

Chemicals and substances labeled as carcinogens can have different levels of cancer-causing potential.

Even if something is a carcinogen, this does not mean it causes cancer in everyone exposed to it:

• Some might increase cancer risk after only a short exposure.
• Others might cause cancer after prolonged, high levels of exposure.

Although some carcinogens clearly raise a person’s risk of 1 or more types of cancer, even the strongest carcinogens don’t raise the risk of all types of cancer.

A person’s risk of developing cancer depends on many factors, including how they are exposed to a carcinogen, the length and intensity of the exposure, their genetic makeup, and current health problems they may have.

How are causes of cancer studied?

Testing whether something causes cancer is often difficult. Most of the time, scientists must test possible carcinogens in lab studies. This is because it isn’t ethical to test a substance on people to determine whether they get cancer from it. Instead, Scientists test on cell cultures and animals.

Scientists also use epidemiology studies, which follow groups of people over time. These studies help show whether something in the environment might lead to a higher risk of cancer.

What lab studies can show

Almost all carcinogens are first tested in labs and on lab animals. But these tests don’t always clearly show whether the results will be the same for people. This is because:

• Lab studies can use very high doses of the chemical or substance being tested. Often the normal exposure for humans is less than exposure in the lab test, meaning the results in people may not be the same.
• Results can vary based on how the tests are done. For example, the effects of a substance that is inhaled may not be the same as when it is applied to the skin.
• The bodies of lab animals and humans don't always process substances in the same way.

Even with these limits, when testing shows that an exposure causes cancer at larger doses in the lab, scientists assume it may also cause cancer in people. This helps protect people from exposures that could raise cancer risk, even before all the effects in humans are fully understood.

What epidemiology studies (studies in people) can show

Another important way to identify possible carcinogens is through epidemiology studies. These studies look at patterns of a disease, like cancer, in groups of people to find out what might be causing the disease.

Epidemiology studies can provide useful information, but they also have limits. This is because humans don’t live in a controlled environment. People can be exposed to many substances or chemicals at any given time and the type and length of exposure can change over time. This can make it hard to know which factors might be linked to cancer.

Even with these limits, epidemiology studies can help scientists find patterns that can help show whether certain exposures may be linked to a higher cancer risk.

What are the different carcinogen classifications?

Several national and international agencies review evidence from lab and epidemiology studies to determine the level of cancer-causing potential of different substances. By combining data from studies, scientists can better understand whether something might cause cancer.

When the studies are complete, the substance or chemical is classified into 1 of these categories:

• Carcinogen: The studies are conclusive, meaning the exposure or substance is known to cause cancer.
• Probable carcinogen: The studies suggest a link to cancer, but are not conclusive.
• Possible carcinogen: Studies show limited evidence that is far from being conclusive.
• Not classified: Study results do not show enough evidence to determine if the substance causes or might cause cancer.
• Probably not a carcinogen: Studies show the substance likely does not cause cancer. This classification is rarely used.

Different agencies may use other, more specific classifications as well, because each has its own system for grouping carcinogens.

Who determines how carcinogens are classified?

Two key organizations classify carcinogens:

• International Agency for Research on Cancer (IARC) based in France
• National Toxicology Program (NTP) based in the US

The IARC and NTP work independently. They each publish lists of carcinogens. Many of the chemicals, substances, and exposures in the lists are the same.

Other US agencies that might be involved include:

• Environmental Protection Agency (EPA)
• National Institute for Occupational Safety and Health (NIOSH)
• Food and Drug Administration (FDA)
• National Cancer Institute (NCI)

International Agency for Research on Cancer (IARC)

The IARC is the specialized cancer agency of the World Health Organization (WHO). One of its major goals is to identify causes of cancer. The most widely used system for classifying carcinogens comes from the IARC:

• Group 1: Carcinogenic to humans
• Group 2A: Probably carcinogenic to humans
• Group 2B: Possibly carcinogenic to humans
• Group 3: Not classifiable as to its carcinogenicity in humans

The IARC publishes its findings as monographs that are open to the public. The monographs include detailed evidence from studies that support the classification. Learn more about IARC classifications and monographs at https://monographs.iarc.fr/agents-classified-by-the-iarc/.

US National Toxicology Program

The NTP is part of 3 US federal government agencies within the Department of Health and Human Services:

• The National Center for Toxicological Research (NCTR), part of the FDA
• The National Institute of Environmental Health Sciences (NIEHS), part of the National Institutes of Health (NIH)
• NIOSH, part of the Centers for Disease Control and Prevention (CDC)

These NTP partners work together to identify potentially harmful substances and evaluate their effects on human health. The NTP also publishes the Report on Carcinogens (RoC) every few years. The report identifies 2 groups of agents:

• Known to be human carcinogens
• Reasonably anticipated to be human carcinogens

Learn more about the latest report at https://ntp.niehs.nih.gov/research/assessments/cancer/roc.

State agencies and groups

Some state agencies also keep lists of known or probable carcinogens. For example, the California Environmental Protection Agency (CalEPA) maintains a list of “chemicals known to the state to cause cancer or reproductive toxicity.” Much of this list is based on the IARC and NTP lists. Learn more in Cancer Warning Labels Based on California’s Proposition 65.

The American Cancer Society’s role

In general, the American Cancer Society does not determine whether something should be considered a carcinogen. Instead, we look to other respected organizations for help with this.

The American Cancer Society (ACS) contributes to evaluating if and how environmental factors can affect a person's risk of developing cancer:

• Doing epidemiology studies on the causes of cancer
• Helping to fund research done by  universities and other institutions that look at how the environment affect cancer risk
• Advocating for environmental health to legislators at local, state, and federal levels
• Informing the public about environmental and other factors that can affect cancer risk and how people can lower their risk of developing cancer

Additional Resources

Along with ACS, other sources of information include:

International Agency for Research on Cancer (IARC)

• Website: www.iarc.fr
• IARC Carcinogen Monographs: http://monographs.iarc.fr

National Toxicology Program (NTP)

• Website: http://ntp.niehs.nih.gov
• Report on Carcinogens Fact Sheet: https://ntp.niehs.nih.gov/sites/default/files/ntp/pressctr/factsheet/15th_roc_508.pdf
• Full report on Carcinogens: https://ntp.niehs.nih.gov/research/assessments/cancer/roc

Environmental Protection Agency (EPA)

• Website: www.epa.gov
• Integrated Risk Information System: www.epa.gov/iris

Food and Drug Administration (FDA)

• Website: www.fda.gov
• Harmful and Potentially Harmful Constituents (HPHCs): https://www.fda.gov/tobacco-products/products-ingredients-components/harmful-and-potentially-harmful-constituents-hphcs
• Food Chemical Safety: https://www.fda.gov/food/food-ingredients-packaging/food-chemical-safety

National Cancer Institute

• Website: www.cancer.gov
• Cancer Causes and Risk Factors: www.cancer.gov/cancertopics/causes
• Causes and Prevention Research: https://www.cancer.gov/about-cancer/causes-prevention/research

National Institute for Occupational Safety and Health (NIOSH)

• Website: www.cdc.gov/niosh
• Safety and Health Topics – Carcinogens: https://www.osha.gov/carcinogens
• NIOSH Safety and Health Topic – Occupational Cancer: www.cdc.gov/niosh/cancer/about/index.html
• Pocket Guide to Chemical Hazards: https://www.cdc.gov/niosh/npg/

*Inclusion on this list does not imply endorsement by the American Cancer Society.