Cancer is a major public health problem worldwide and a leading cause of death. In 2018, there were 18.1 million new cases and 9.6 million deaths from cancer worldwide. Understanding the causes of cancer is critical for developing preventive strategies and treatments.
What causes cancer?
Cancer is caused by changes to the DNA within cells. The DNA inside a cell is packaged into chromosomes. Changes in the DNA sequence can result in altered instructions for cell growth, division and death. There are several factors that can cause changes to DNA and lead to cancer:
- Genetic factors – Inherited genetic mutations can make some individuals more prone to developing certain cancers. Gene mutations can be passed from parent to child.
- Lifestyle factors – Tobacco use, alcohol consumption, UV light exposure from the sun, ionizing radiation, obesity and lack of exercise can all contribute to cancer development.
- Pathogens – Viruses, bacteria and parasites are able to cause DNA damage and chronic inflammation, which can eventually lead to cancer.
- Environmental factors – Carcinogenic chemicals, air pollution and pesticides are environmental exposures that increase cancer risk.
Therefore, there are many different external agents and internal factors that can lead to the genetic mutations and cellular changes behind cancer. But are pathogens responsible for all cancers? There is evidence that certain pathogens contribute to specific cancer types, but they do not account for every case of cancer.
How do pathogens cause cancer?
Pathogens are infectious agents such as viruses, bacteria and parasites. There are several ways in which pathogens can contribute to cancer development:
- Insertion of viral DNA into the human genome – This can disrupt tumor suppressor genes or other key regulatory genes. For example, human papillomavirus (HPV) inserts DNA into the host genome which can lead to cervical cancer development.
- Chronic inflammation – Persistent infections cause ongoing inflammation which produces free radicals and DNA damaging agents. Helicobacter pylori bacterial infection in the stomach lining can trigger gastric cancer.
- Weakened immunity – HIV infection and other diseases causing immunodeficiency allow opportunistic pathogens to take hold.
- Toxins – Bacterial toxins have been associated with some liver and other gastrointestinal cancers.
Therefore, pathogens promote cancer through direct mutagenic effects as well as indirect influence on the cellular environment and host immunity. However, even known oncogenic pathogens are not sufficient by themselves to cause cancer – other cofactors are required.
Examples of cancers caused by pathogens
While many pathogens have been associated with specific cancer types, the International Agency for Research on Cancer (IARC) has classified the following biological agents as definitive human carcinogens:
| Pathogen type | Cancer association |
|---|---|
| Hepatitis B and C viruses (HBV and HCV) | Liver cancer |
| Human T-cell lymphotropic virus type 1 (HTLV-1) | Adult T-cell leukemia/lymphoma |
| Epstein-Barr virus (EBV) | Hodgkin lymphoma, Burkitt lymphoma, nasopharyngeal carcinoma, gastric carcinoma |
| Human immunodeficiency virus type 1 (HIV-1) | Kaposi sarcoma, non-Hodgkin lymphoma |
| Human papillomavirus (HPV) types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59 | Cervical, anogenital and a subset of head and neck cancers |
| Helicobacter pylori | Gastric cancer |
| Schistosoma haematobium (parasite) | Bladder cancer |
| Opisthorchis viverrini (liver fluke parasite) | Cholangiocarcinoma (bile duct cancer) |
| Clonorchis sinensis (liver fluke parasite) | Cholangiocarcinoma and possibly liver cancer |
These represent infections that have sufficient evidence of a causal relationship with specific cancer types. However, even for well-established oncogenic pathogens, infection alone is typically not sufficient for cancer development. Other cofactors like host genetics, diet, smoking and alcohol use act together with pathogens to progress to full malignancy.
Key examples
HPV and cervical cancer
HPV is responsible for nearly all cases of cervical cancer worldwide. HPV inserts viral oncoproteins into infected cervical cells which inactivate the p53 and pRb tumor suppressor pathways. However, additional genetic mutations are required for progression to invasive cervical cancer. Cofactors like smoking greatly increase this risk. HPV vaccines provide effective prevention against the high risk cancer-associated HPV strains.
H. pylori and gastric cancer
H. pylori colonizes the stomach lining and causes chronic inflammation. The bacteria inject the CagA toxin into gastric epithelial cells which alters cell signaling and promotes malignant transformation. However, H. pylori infection alone usually does not lead to stomach cancer. Factors like a high-salt diet, smoking and host genetic susceptibility are important additional cofactors.
Hepatitis viruses and liver cancer
Chronic HBV and HCV infection causes liver inflammation and cirrhosis. This provides a favorable environment for accumulating somatic mutations and the eventual development of hepatocellular carcinoma. Co-existing diabetes, alcohol abuse and aflatoxin exposure further amplify the risk of liver cancer.
Cancers not known to be caused by pathogens
While pathogens contribute significantly to the global cancer burden, the majority of cancer types have no definitive links to infectious agents. Here are some examples of major cancers with no proven microbial cause:
- Breast cancer
- Prostate cancer
- Lung cancer
- Colorectal cancer
- Pancreatic cancer
- Ovarian cancer
- Brain cancer
- Bone cancer
- Skin cancers (melanoma)
- Leukemias and lymphomas (excluding pathogen-associated subtypes)
The development of these cancers primarily involves genetic mutations related to aging, carcinogen exposure, hereditary factors and somatic DNA mutations. Chronic inflammation not triggered by pathogens may also contribute. Some studies have searched for viral involvement in cancers like breast and prostate, but no causative agents have been identified.
Conclusions
In summary, while pathogens contribute significantly to the global cancer burden, especially in less developed regions, they do not account for all cancer cases worldwide. Well-established oncogenic pathogens include HPV, hepatitis viruses, H. pylori, EBV and parasitic liver flukes. However, many other major cancer types have no proven pathogen association based on current evidence. Limitations in proving causation may exist in some cases. Nonetheless, the majority of cancers are still attributed to genetic and environmental factors aside from pathogens. Cancer is a complex, multifactorial disease. Continuing research on both infectious and non-infectious causes of cancer is important for improving prevention and treatment.
