Multifactorial Etiology of Cancer: Genetic, Environmental, and Lifestyle Determinants in Oncogenesis

Cancer is one of the leading causes of death worldwide, affecting millions of people each year. Despite the medical and technological advancements that have been made, this complex group of medical diseases have plagued doctors, scientists and families. Understanding what cancer is, how it develops, and what can be done to prevent or treat it is more important now than ever. 

Now, before understanding how cancer affects the human body, we need to first understand what exactly cancer is. According to the National Cancer Institute, “Cancer is a disease in which some of the body’s cells grow uncontrollably and spread to other parts of the body.” Cancer has the ability to start anywhere in the human body, and the area of which the cancer starts is usually characterized by its name. The type of cancer usually characterizes which organ or tissue the cancerous cells develop in, despite it spreading to a different location along the human body. Cancer in the body is usually formed by the multiplication of abnormal or damaged cells. The human body produces new cells by cell division, causing cells to divide in numbers and therefore causing them to multiply in populations. When a cell completes its life cycle of approximately 7 to 10 years, the cell dies. But sometimes, this orderly process breaks down, and abnormal or damaged cells multiply with cell division when they shouldn’t. This process can cause the formation of tumors (lumps of tissue), which can either be cancerous or non-cancerous (benign). Tumors are often not cancerous (malignant) and the chances of them being cancerous aren’t very high. Cancer spreads through the cancerous tissue invading nearby tissues and infecting them to become cancerous as well. This causes the nearby tissues to develop into tumors, and this process is called metastasis. Cancerous tumors can also be referred to as malignant tumors as cancerous tissues are often characterized as “malignant” while non-cancerous tissues are characterized as “benign”. Cancers usually form solid tumors but blood cancers, such as leukemias, generally do not. 

Now that we have understood what cancer is and how it is formed within the human body, let’s understand what are the external factors that cause cancer. While there is no single cause for cancer, many scientists such as Robert Weinberg, Bert Vogelstein, Ana Soto and so much more. These several factors can include genetic, environmental and the constitutional characteristics of the individual. The genetic factors that can cause cancer include inherited mutations, family history and gene-environment interactions. Some individuals inherit mutations from their parents or their relatives such as in BRCA1 and BRCA2. BRCA1 and BRCA2 (or also known as BRCA1/2) are tumor suppressor genes that play a critical role in DNA repair. Mutations that occur in this gene significantly increase the chances of breast and ovarian cancer in men and women. The diagram below allows us to visualize the percentile rate of risk that mutations occurring in the BRCA1/2 genes can cause breast (both female and male), pancreatic (both female and male), ovarian (only in females) and prostate cancer (only in males).

Another genetic factor that increases cancer risk includes a strong history of cancer in a family. This could indicate and determine a genetic predisposition for the current individual to have a higher risk of developing cancer. While most cancers are not linked to inherited gene changes, breast cancer and prostate cancer have the strongest genetic component and therefore are the most heritable. Having a family history for breast and prostate cancer can significantly increase an individual’s risk rate of developing breast and prostate cancer. While the percentile risk of developing breast cancer increases significantly with a family history as said before, the exact number depends on factors like the number of relatives affected, their age at diagnosis and whether the family carries specific genetic mutations like the BRCA1/2. The general population risk with breast cancer (I’m going to be using breast cancer for this example) without a family history is an approximation of 12%, so about 1 in 8 women. Now, to look at how the risk percentile increases with the affected family history. If one first-degree relative such as a mother, sister or daughter has been affected by breast cancer, the estimated lifetime risk is about 15-20%. In comparison, if two first-degree relatives have had breast cancer, then the estimated lifetime risk increases to an approximation of 30-40% risk. And a family history of BRCA1 or BRCA2 gene mutation can lead to a lifetime risk of 55-70% with BRCA1 and a 45-60% with BRCA2. The table below will aid you in your understanding. Note that this table only provides information on breast cancer. 

The final genetic factor includes gene-environment interaction in cancer. This concept explains that having a genetic predisposition alone is often not enough to cause cancer, and that environmental roles also play a crucial role in activating or triggering the disease. The key ideas include understanding that a genetic predisposition is conducive to a higher susceptibility but certain activities done by the individual can lead to actually developing cancer within their body. Such that having a BRCA1/2 mutation increases the baseline risk of breast and ovarian cancer, it often depends on avoidable or life-style related components to develop the cancer. The environmental triggers often are exposure (usually at a prolonged and concentrated rate) to harmful agents including UV radiation, tobacco smoke, alcohol, certain viruses and toxic chemicals that can damage DNA or influence gene expression. The concept goes that an individual with a risky gene may not develop cancer unless they also encounter certain environmental scenarios. An example is as follows, a woman with a BRCA1 mutation who uses hormone replacement therapy (a treatment that involves using synthetic hormones to supplement or replace natural hormones when the body is not producing enough.) may be at a higher risk than someone with the same BRCA1 mutation who doesn’t use hormone replacement therapy. Likewise, someone with Li-Fraumeni syndrome (a mutation in TP53, TP53 is a tumor suppressor gene that produces a protein called p53.) is more likely to develop cancer after radiation exposure than someone without the mutation. And people with variations in detoxification genes (like CYP1A1) are at a greater risk from smoking than others. From this, we can understand that gene-environment interaction means that genes set the stage, but the environment pulls the trigger. The risk of cancer is amplified when genetic vulnerability is combined with harmful exposures. 

Environmental factors such as exposure to Ultraviolet radiation of ionizing radiation can damage DNA. This can occur through both direct and indirect mechanisms. Direct damage occurs when radiation directly hits and ionizes DNA molecules, causing breaks and mutations. Indirect damage happens when radiation interacts with surrounding molecules, like water, to produce free radicals that then damage DNA. Ionization is an electrochemical process in which radiation releases electrons from atoms in DNA, creating charged ions (splitting them into cations and anions). Like in chemistry, when electricity is passed through a compound, the compound breaks into two simpler compounds or elements that are either positively or negatively charged to create an electrochemical reaction. The same thing occurs with the structure of DNA, causing breaks in the sugar phosphate backbone or altering the nucleotide bases. The consequences of DNA damage include mutations, cell death, chromosomal aberrations, genomic instability and bystander effects. 

Mutations cause alterations in gene function and potentially cause diseases like cancer. Cell death is usually caused if the DNA damage is too severe, this causes cells to undergo programmed cell death, also known as apoptosis. Chromosomal aberrations can cause disruptions in cell division and can also increase cancer risks. DNA damage can also lead to long-term changes in the genome which can make it more susceptible to further mutations and abnormalities in cells. 

It is also widely acknowledged that lifestyle factors such as smoking, diet, alcohol and physical inactivity/obesity increase risks of cancer. Smoking is a major cause of lung cancer along with other lung diseases such as asthma, tuberculosis, chronic bronchitis and et cetera. Diet such as high consumption of processed food, red meats and a low fiber can increase cancer risks. Increased consumption of alcohol and drugs increase the risk of several types of cancers, including liver, breast and esophageal cancers. Obesity and lack of physical activity can lead to breast and colon cancers. Thus, by addressing modifiable risk factors such as smoking, poor diet, alcohol use, and physical inactivity, individuals can take meaningful steps toward lowering their chances of developing cancer.

In summary, cancer remains one of the most significant health challenges faced globally, arising from a variety of genetic, environmental, and lifestyle factors. Understanding how cancer originates—from the uncontrolled division of abnormal cells to the spread of malignant tumors—highlights the importance of early detection and prevention. While some individuals may carry genetic mutations that increase their risk, environmental exposures and lifestyle decisions often act as the catalysts that trigger the disease. Therefore, public awareness and personal responsibility are vital in reducing cancer incidence. By making healthier lifestyle choices, minimizing exposure to known carcinogens, and seeking regular medical screenings, individuals can take proactive steps to protect themselves. Continued research and education are essential in the fight against cancer, offering hope for improved treatment, prevention, and ultimately, a cure.