Chapter 03 Risk Factors

Human Carcinogens

Almost 130 agents have been classified as having sufficient evidence to cause cancer in humans.

The IARC Monographs identify the causes of human cancer. Sometimes called the World Health Organization’s “Encyclopedia of Carcinogens,” the IARC Monographs are systematic evaluations of the strength of evidence that an agent can cause cancer in humans. Since the program’s inception in 1971, over 1,040 agents have been evaluated, including chemicals, complex mixtures, physical and biological agents, personal habits, and occupational exposures.

The agents are classified as carcinogenic to humans (Group 1), probably carcinogenic to humans (Group 2A), possibly carcinogenic to humans (Group 2B), or not classifiable as to their carcinogenicity to humans (Group 3). This classification, based on publicly available scientific literature, reflects evidence derived from studies of cancer in humans, cancer in experimental animals, and studies on carcinogen mechanisms in exposed humans, experimental animals, and in-vitro systems. Evidence from human and animal studies of cancer is considered as sufficient, limited, inadequate, or suggesting lack of carcinogenicity. Mechanistic evidence from in-vitro studies is considered as strong, limited, or inadequate, based on the key characteristics of carcinogens. To date, 129 agents have been classified in Group 1, mainly on the basis of sufficient evidence from epidemiological studies that the agent can cause one or more cancer types in humans, and with some agents classified based on sufficient evidence for cancer in experimental animals and strong evidence in exposed humans for the key characteristics of carcinogens.

Some important risk factors for cancer in humans have not been evaluated by the Monographs program, notably genetic traits, reproductive status, and other diseases (e.g., diabetes), while certain protective factors, such as weight control, physical activity, or reduction of alcohol consumption (see Body Fatness, Physical Activity, and Diet and Alcohol) have been evaluated by the IARC Handbooks. However, excess body fatness and sedentary behavior may be topics of future Monographs evaluations.

Figure 3.1 shows which agent(s) have sufficient evidence of causing cancer for each organ or group of organs in the human body.

Figure 3.1

Group 1 (carcinogenic to humans) agents by target organ site

CA4
Site
Agent
Brain and Central Nervous System
X-radiation, gamma radiation
Eye
  • Human immunodeficiency virus type 1 (HIV)
  • Ultraviolet-emitting tanning devices
  • Welding
Oral Cavity & Pharynx
Oral Cavity
  • Alcoholic beverages
  • Betel quid with tobacco
  • Betel quid without tobacco
  • Human papillomavirus type 16
  • Smokeless tobacco
Pharynx (Oro-, Hypo- and not otherwise specified)
  • Alcoholic beverages
  • Betel quid with tobacco
  • Human papillomavirus type 16
  • Smoking tobacco
Salivary Gland
  • X-radiation, gamma radiation
Respiratory System
Nasal Cavity and Paranasal Sinus
  • Isopropyl alcohol manufacture using strong acids
  • Leather dust
  • Nickel compounds
  • Radium-226 and its decay products
  • Radium-223 and its decay products
  • Tobacco smoking
  • Wood dust
Larynx
  • Acid mists, strong inorganic
  • Alcoholic beverages
  • Asbestos (all forms)
  • Smoking tobacco
Lung
  • Achaean process (occupational exposures associated with)
  • Aluminium production
  • Arsenic and inorganic arsenic compounds
  • Asbestos (all forms)
  • Beryllium and beryllium compounds
  • Bis(chloromethyl)ether; chloromethyl methyl ether (technical grade)
  • Cadmium and cadmium compounds
  • Chromium (VI) compounds
  • Coal, indoor emissions from household combustion
  • Coal gasification
  • Coal-tar pitch
  • Coke production
  • Diesel engine exhausts
  • Hematite mining (underground)
  • Iron and steel founding
  • MOPP (vincristine-prednisone nitrogen mustard–procarbazine mixture)
  • Nickel compounds
  • Outdoor air pollution
  • Outdoor air pollution, particulate matter
  • Painter (occupational exposure as)
  • Plutonium
  • Radon-222 and its decay products
  • Rubber production industry
  • Silica dust, crystalline
  • Soot
  • Sulfur mustard
  • Tobacco smoke, secondhand
  • Tobacco smoking
  • X-radiation, gamma-radiation
  • Welding fumes
Mesothelium
  • Asbestos (all forms)
  • Erionite
  • Firefighter (occupational exposure as)
  • Fluoro-edenite
  • Painter (occupational exposure as)
Thyroid
  • Radioiodines, including iodine-131 (exposure during childhood and adolescence)
  • X-radiation, gamma-radiation
Hematopoietic System
  • Azathioprine
  • Benzene
  • Busulfan
  • 1,3-Butadiene
  • Chlorambucil
  • Cyclophosphamide
  • Cyclosporine
  • Epstein-Barr virus
  • Etoposide with cisplatin and bleomycin
  • Fission products, including Strontium-90
  • Formaldehyde
  • Helicobacter pylori
  • Hepatitis C virus
  • HIV type 1
  • Human T-cell lymphotropic virus type 1
  • Kaposi sarcoma herpes virus
  • Lindane
  • Melphalan
  • MOPP (vincristine-prednisone-nitrogen mustard-procarbazine mixture)
  • Pentachlorophenol
  • Phosphorus-32, as phosphate
  • Rubber production industry
  • Semustine [1-(2-Chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea, or methyl-CCNU]
  • Thiotepa
  • Thorium-232 and its decay products
  • Tobacco smoking
  • Treosulfan
  • X-radiation, gamma-radiation
Skin
Melanoma
  • Solar radiation
  • Polychlorinated biphenyls
  • Ultraviolet-emitting tanning devices
Other Malignant Neoplasms
  • Arsenic and inorganic arsenic compounds
  • Azathioprine
  • Coal-tar distillation
  • Coal-tar pitch
  • Cyclosporine
  • Methoxsalen plus ultraviolet A
  • Mineral oils, untreated or mildly treated
  • Shale oils
  • Solar radiation
  • Soot
  • X-radiation, gamma-radiation
Bone
  • Plutonium
  • Radium-224 and its decay products
  • Radium-226 and its decay products
  • Radium-228 and its decay products
  • X-radiation, gamma-radiation
Breast
  • Alcoholic beverages
  • Diethylstilbestrol
  • Estrogen-progestogen contraceptives
  • Estrogen-progestogen menopausal therapy
  • X-radiation, gamma-radiation
Digestive System
Esophagus
  • Acetaldehyde associated with consumption of alcoholic beverages
  • Alcoholic beverages
  • Betel quid with tobacco
  • Betel quid without tobacco
  • Smokeless tobacco
  • Tobacco smoking
  • X-radiation, gamma-radiation
UPPER AERODIGESTIVE TRACT
  • Acetaldehyde associated with consumption of alcoholic beverages
STOMACH
  • Helicobacter pylori
  • Rubber production industry
  • Tobacco smoking
  • X-radiation, gamma-radiation
LIVER (ANGIOSARCOMA)
  • Vinyl chloride
LIVER (HEPATOCELLULAR CARCINOMA)
  • Aflatoxins
  • Alcoholic beverages
  • Estrogen-progestogen contraceptives
  • Hepatitis B virus
  • Hepatitis C virus
  • Plutonium
  • Thorium-232 and its decay products
  • Tobacco smoking (in smokers and in smokers' children)
GALLBLADDER
  • Thorium-232 and its decay products
BILIARY TRACT
  • Chlonorchis sinensis
  • 1,2-Dichloropropane
  • Opisthorchis viverrini
PANCREAS
  • Smokeless tobacco
  • Tobacco smoking
COLON AND RECTUM
  • Alcoholic beverages
  • Processed meat (consumption of)
  • Tobacco smoking
  • X-radiation, gamma-radiation
ANUS
  • HIV type 1
  • Human papillomavirus type 16
Urinary System
KIDNEY
  • Tobacco smoking
  • Trichloroethylene
  • X-radiation, gamma-radiation
RENAL PELVIS
  • Aristolochic acid, plants containing
  • Phenacetin
  • Phenacetin, analgesic mixtures containing
  • Tobacco smoking
URINARY BLADDER
  • Aluminum production
  • 4-Aminobiphenyl
  • Arsenic and inorganic arsenic compounds
  • Auramine production
  • Benzidine
  • Chlornaphazine
  • Cyclophosphamide
  • Firefighter (occupational exposure as)
  • Magenta production
  • 2-Naphthylamine
  • Opium consumption
  • Painter (occupational exposure as)
  • Rubber production industry
  • Schistosoma haematobium
  • Tobacco smoking
  • ortho-Toluidine
  • X-radiation, gamma-radiation
URETER
  • Aristolochic acid, plants containing
  • Phenacetin
  • Phenacetin, analgesic mixtures containing
  • Tobacco smoking
Genital System
Uterine Cervix
  • Diethylstilbestrol (exposure in utero)
  • Estrogen-progestogen contraceptives
  • HIV type 1
  • Human papillomavirus type 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59
  • Tobacco smoking
Endometrium
  • Estrogen menopausal therapy
  • Estrogen-progestogen menopausal therapy
  • Tamoxifen
Ovary
  • Asbestos (all forms)
  • Estrogen menopausal therapy
  • Tobacco smoking
Vagina
  • Human papillomavirus type 16
Vulva
  • Human papillomavirus type 16
Penis
  • Human papillomavirus type 16
Multiple Sites (Partly Unspecified)
  • Cyclosporine
  • Fission products, including Strontium-90
  • X-radiation, gamma-radiation (exposure in utero)
All Cancers Combined
  • 2,3,7,8-Tetrachlorodibenzo-para-dioxin
Endothelium (Kaposi Sarcoma)
  • HIV type 1
  • Kaposi sarcoma herpes virus
Less Than Sufficient Evidence in Humans*
  • Areca nut
  • Aristolochic Acid
  • Benzidine, dyes metabolized to
  • Benzo[a]pyrene
  • Ethanol in alcoholic beverages
  • Ethylene oxide
  • Etoposide
  • Ionizing radiation (all types)
  • 4,4'-Methylenebis (1-chloroaniline) (MOCA)
  • Neutron radiation
  • N'-Nitrosonornicotine, (NNN) and 4-(N-nitro-methyl-amino-1-(3-pyridyl)-1-but none (NNK)
  • 2,3,4,5,8-Pentachlorodibenzofuran
  • 3,4,5,3',4'-Pentachlorobiphenyl (PCB-126)
  • Perfluorooctanoic acid (PFOA)
  • Polychlorinated biphenyls dioxin like, with a Toxic Equivalent Factor according to WHO (PCBs 77, 81, 105, 114, 118, 123, 126, 156, 167, 169, 189)
  • Radionuclides, alpha-particle emitting, internally deposited
  • Radionuclides, beta-particle emitting, internally deposited
  • Ultraviolet radiation

The number of such agents for the most common cancer types (lung, breast, colorectum, prostate, stomach, and liver) is highly variable. For example, there are 32 known causes of lung cancer, but no known causes of prostate cancer identified by the Monographs program. Over 40 agents cause cancer in more than one target organ site, with tobacco causing cancer in 17 sites and X-radiation and gamma-radiation in 14 sites (Figure 3.2).

Over 40 agents cause cancer in more than one target organ site with tobacco causing cancer in 17 sites.

Figure 3.2

IARC Monograph Group 1 (carcinogenic to humans) agents associated with four or more cancer types, 2024

Footnote

Major cancer site groupings: some types are combined.

Sources

Text

  • International Agency for Research on Cancer. List of Classifications - IARC Monographs on the Identification of Carcinogenic Hazards to Humans. https://monographs.iarc.who.int/list-of-classifications. Accessed July 12, 2024.
  • IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, International Agency for Research on Cancer. Outdoor Air Pollution: IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. Vol. 109, IARC monographs. Lyon, France: International Agency for Research on Cancer; 2016.
  • IARC Monographs on the Identification of Carcinogenic Hazards to Humans. Lyon (FR): International Agency for Research on Cancer; 1987-. https://www.ncbi.nlm.nih.gov/books/NBK294452/.
  • Loomis D, Guha N, Hall AL, Straif K. Identifying occupational carcinogens: an update from the IARC Monographs. Occup Environ Med. Aug 2018;75(8):593-603. doi:10.1136/oemed-2017-104944
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