Recent insights into the causes and development of cancer
Cancer develops when cells in the body grow and divide uncontrollably, due to mutations (mistakes) in cell DNA. Recent insights into the causes of cancer and how cancer cells develop in the body indicate that the uncontrolled growth of cancer cells results from different factors and an accumulation of abnormalities that affect many of the regulatory mechanisms of the cell, such as:
- Abnormalities in the mechanisms that normally regulate cell proliferation, which refers to the growth of a cell in mass and size as well as cell division, which refers to the process in which a parent cell divides to form two daughter cells.
- Abnormalities in the mechanisms that normally regulate cell differentiation, which refers to the process by which a less specialized cell changes into a specific cell type with a distinct structure and function.
- Abnormalities in the mechanisms that normally regulate cell survival, such as that healthy cells only divide when conditions are right, normal signaling networks and stress response pathways in the cell, as well as programmed cell death.
Together, this accumulation of cell abnormalities indicates malignancy at the cellular level. A defining feature of cancer is the rapid creation of abnormal cells that grow beyond their usual boundaries, making it possible to invade adjoining areas, and to spread to other organs in the body, a process called metastasis.
The development of cancer.
A fundamental feature of the development of cancer is tumor clonality, which refers to the concept that most cancers originate from a single cell that begins to proliferate by growing in size and dividing in two identical daughter cells to form a genetically identical clone of the original cell.
All the cells in a tumor, and when and where metastasis occurs, share the same initial set of abnormal mutations from the original cell.
How this works, is that the single original cell develops an accumulating series of genetic and epigenetic alterations, which stimulates growth. When this single cell divides, the mutations are passed on to the daughter cells and they in turn to their daughter cell “clones” to create a population of cells that are genetically identical to the original cell. As this population of “clones” grows, it can acquire new mutations, which can lead to “subclones” with even greater growth advantages.
The clonal origin of tumors does not mean that the original cell that gives rise to a tumor has initially had all of the characteristics of a cancer cell. The development of cancer is a multistep process, in which cells gradually become malignant through a progressive series of alterations. The dramatic increase of cancer incidence with age is an indication that most cancers develop as a consequence of multiple abnormalities that accumulate over periods of many years. An example in this regard is the incidence of colon cancer which increases more than tenfold between the ages of 30 and 50, with another tenfold increase between the ages of 50 and 70.
The multistep process in the development of cancer has tumor initiation as its first step, which is thought to result from a genetic alteration in the DNA in the cell, due to a variety of external influences and mostly not inherited, leading to the abnormal proliferation of a single cell. Cell proliferation then leads to the outgrowth of a population of “cloned” tumor cells (tumour promotion). Tumor progression then continues as additional mutations occur within the cells of the tumor population.
Some of these additional mutations gives the “clone” a selective advantage, with properties such as more rapid growth, invasion, or metastasis, and the descendants of such cells will have an advantage and consequently become dominant within the tumor population. This process is called clonal selection, as a new clone of tumor cells has evolved. Clonal selection continues throughout tumor development, which results in tumors continuously becoming more rapid-growing and increasingly malignant.
Proving tumor clonality is important, as scientists can analyze the genetic makeup of a tumor to confirm clonality. The results would indicate whether a second tumor in a patient is a metastasis of the original tumor, or a new primary tumor. This information is vital in treatment planning for the patient.
Causes of cancer:
Substances that cause cancer are called carcinogens and have been identified by animal studies as well as epidemiological analysis of cancer frequencies in human populations, for example the high incidence of lung cancer among cigarette smokers. Epidemiological studies look at factors such as genetics, environment, and lifestyle to understand the incidence, prevalence, and mortality trends of cancer, in order to identify risk factors and develop prevention and control strategies.
The development of cancer is a complex, multistep process with many factors affecting the likelihood of developing cancer and it is regarded as overly simplistic to refer to single causes of most cancers. However, many factors, including radiation, chemicals, and viruses have been found to cause cancer.
Carcinogens that damage DNA and induce mutations: Radiation such as from the sun’s ultraviolet rays and many chemical carcinogens are referred to as initiation agents, whose induction of mutations in certain genes is viewed as the initial event leading to cancer development. Some of the initiation agents that contribute to cancer are:
- Solar ultraviolet radiation is regarded as the main cause of skin cancer.
- Certain carcinogenic chemicals have been identified as major causes of cancer and are found in, for example, tobacco smoke, which contains, amongst others, nickel compounds, benzopyrene, and dimethylnitrosamine. Smoking is an undisputed cause of 80 to 90% of lung cancer cases and is also linked to cancers of the oral cavity, pharynx, larynx, and esophagus. Smoking is linked to nearly one-third of all cancer deaths. Other examples of carcinogenic chemicals are asbestos fiber, arsenic found in some drinking water, and ethanol (a known carcinogen) in alcoholic drinks, including wine, beer and liquor.
- Aflatoxin is produced by some molds that thrive in warm, humid conditions and can contaminate crops such as improperly stored supplies of peanuts, corn, tree nuts, spices, as well as animal feeds and subsequently in milk products from animals that consume contaminated feed. Aflatoxin is a potent liver carcinogen.
Carcinogens that stimulate cell proliferation: Some carcinogens contribute to cancer development by stimulating cell proliferation, instead of inducing the original mutations. These carcinogens are referred to as tumor promotors (and not initiators), since they induce increased cell division during early stages of tumor development.
Hormones can stimulate cell proliferation: Hormones such as estrogens can promote the development of cancer by accelerating the growth of cancer cells and influence the immune system to create conditions that are favorable for tumor growth. For example, the proliferation of cells in the uterine endometrium, the innermost layer of the uterus, is stimulated by estrogen.
Several viruses are linked to cancer: A virus must enter a living cell in order to reproduce and make more viruses. Some viruses do this by inserting their own DNA into the DNA of the host cell, which can influence the cell toward becoming cancerous, by disrupting the genes that control cell growth and by causing DNA damage. Generally, each type of virus tends to infect only a certain type of cell in the body, for example the common cold viruses only affect the cells lining the nose and throat. Several viruses are linked to cancer, and the most well-known of these are:
- Human papillomaviruses, which are the main causes of cervical cancer and are also linked to causing some cancers of the vagina, vulva, anus, penis, and mouth and throat.
- Epstein-Bar virus infection increases the risk of cancer in the back of the nose.
- Hepatitis B virus and hepatitis C virus can cause viral hepatitis, a type of liver infection, which can increase a person’s chance of liver cancer.
The incidence of cancer rises dramatically with age, suspected to be due to a build-up of risks for specific cancers that increase with age, combined with the tendency for cellular repair mechanisms that are less effective due to aging.
Genetically inherited causes of cancer:
The traditional view has been that cancer is a genetic disease, with its origin and treatment based on inherited damaged “hardware”, which consists of the genetic material inside the human cell. However, research over the past decade has indicated that cancer may well be a “software” disease, based on the incorrect functioning of the biochemical processes taking place inside the cell. According to the National Cancer Institute in the UK, less than 10% of cancers are thought to be caused by genetic changes passed on from parent to child. Inheriting these changes does not mean the person will definitely develop cancer, but it increases the likelihood of the disease occurring.
Interestingly, the Food and Drug Administration in America has granted marketing authorization (meaning approval) in 2023 to a blood test that detects inherited genetic changes that may increase the risk of certain cancers. The Invitae Common Hereditary Cancers Panel analyzes a person’s blood sample for changes in 47 genes that are linked to hereditary forms of cancer. Results create opportunities for early detection and prevention in families affected by hereditary cancers. Incidentally, the Invitae Common Hereditary Cancers Panel is available in South Africa through an international referral service with laboratories like Pathcare, which facilitates sample handling and shipping to Invitae in the USA.
Reducing cancer risk.
The World Health Organization (WHO), says cancer risk can be reduced through a number of actions, such as maintaining a healthy body weight, not using tobacco, avoiding or reducing consumption of alcohol, eating a heathy diet that includes fruit and vegetables, doing physical activity on a regular basis, avoiding ultraviolet radiation exposure from the sun and artificial tanning devices and using sun protection measures, minimizing occupational exposure to ionizing radiation such as x rays, and reducing exposure to air pollution.
One example of the WHO recommendations being based on scientific fact, is that the importance of regular exercise was highlighted in a UK study of 85 000 adults by the National Institutes of Health and University of Oxford. The study found that individuals who engaged in light- and moderate-to-vigorous-intensity daily physical activity had a lower risk of cancer than individuals who were more sedentary. After a follow up period of nearly six years, the study found that individuals with the highest total amount of daily physical activity had a 26% lower risk of developing cancer, compared to individuals with the lowest amount of daily physical activity.
Conclusion:
According to the World Health Organization between 30 and 50% of cancers can currently be prevented by avoiding risk factors and implementing existing evidence-based prevention strategies. The cancer burden can be reduced through early detection of cancer, and many cancers have a high chance of cure if diagnosed early and treated appropriately.
References:
Cancer. Published 3 February 2025. World Health Organization. (www.who.int)
Daily physical activity, even at light intensities, linked to lower cancer risk. Published 26 March 2025. National Cancer Institute. USA. (www.cancer.gov)
FDA authorizes blood test for assessing risk of hereditary cancers. Published 2 November 2023. National Cancer Institute. USA. (www.cancer.gov)
Study probes awareness of alcohol’s link to cancer. Published 18 January 2023. National Cancer Institute. USA. (www.cancer.gov)
Alcohol tied to 750 000 cancer cases worldwide in 2020. Published 12 August 2021. National Cancer Institute. USA. (www.cancer.gov)
What causes cancer? Published 6 March 2025. Worldwide Cancer Research. (www.worldwidecancerresearch.org)
Cancer causes: 10 most common factors. Published 5 May 2023. Gateway for Cancer Research. (www.gatewaycr.org)
The development and causes of cancer. Published in a book by Cooper G M and Sunderland M A. The Cell: A Molecular Approach. 2nd Edition. 2000. (Sinauer Associates). National Centre for Biotechnology Information. US National Library for Medicine. National Institutes of Health. USA. (www.ncbi.nlm.nih.gov)
Viruses that can lead to cancer. Published online and revised 21 March 2023. American Cancer Society. (www.cancer.org)
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