Before the mid-20th century, infectious diseases were the primary cause of death. However, with the understanding of bacteria and viruses, appropriate prevention measures, vaccine development, and scientific treatment solutions, the incidence and mortality rates of infectious diseases have been greatly reduced. In recent decades, cancer has surged to become a major cause of death. However, this discouraging statistical data has also increased the possibility of prevention or early detection of diseases, as the development of existing technology has made treatments less invasive, relatively inexpensive, and more likely to cure. However, there is also much debate about the origin of cancer. In one's lifetime, there are two battles: one against time and one against space, and cancer is no exception. The culprit of cancer is everywhere because time and space make it difficult for you to hide.

Figure 1. Organ locations of common human cancers

In the 0-19 age group, solid tumors, congenital heart disease, leukemia, and lymphoma have high mortality rates; in the 20-80 age group, cerebrovascular diseases, dementia, solid tumors, etc., are diseases with relatively high mortality rates (Figure 1). Apart from age, according to medical research, there are differences in the incidence and mortality rates of certain cancers between males and females, such as thyroid cancer, which tends to affect females, and prostate cancer, which tends to affect males. There is a certain association between gender and cancer, but not all cancers have a gender-related risk of occurrence. Therefore, the theories of the origin of cancer are also gradually being debated, attempting to explain why normal cells eventually transform into cancer cells, providing us with different perspectives to analyze the process of cancer formation (Figure 2).

Figure 2. Main theories of the origin of cancer

Somatic Mutation Theory: Cancer's "Nest"

The Somatic Mutation Theory posits that cancer arises from genetic mutations within normal cells, which occur due to internal or external factors causing DNA damage. As these mutations accumulate to a certain extent, the control over cell growth and division is lost, leading to tumor formation. This theory emphasizes the crucial role of genetic mutations in cancer development, while also acknowledging the influence of environmental factors and genomic stability on cancer risk.

Cancer Tissue Theory: Not Just a Solo Act

Cancer is a tissue-level challenge involving interactions between normal cells and cancer cells, as well as the coordination of the tumor microenvironment. Cancer cells interact with other cells and release signaling molecules, influencing surrounding cells and promoting tumor growth. This theory highlights the complexity within tumors and the role of intercellular communication in cancer.

Stochastic Theory: Fate Playing Tricks

The Stochastic Theory regards cancer as a stroke of "bad luck," where cellular fate is influenced by random events and unpredictable challenges such as errors in DNA replication. These chance events lead to oncogenic mutations and promote cancer development. This theory emphasizes the role of stochastic factors in the origin of cancer, explaining the occurrence of cancer in the absence of apparent carcinogenic factors.

Predestination Theory: Concealed Mysteries

The Predestination Theory suggests that cells may exist in an abnormal state before becoming cancerous, induced by internal or external factors, making the cells more prone to malignant transformation. This theory underscores the importance of cellular states and plasticity in cancer development, rather than solely focusing on individual DNA mutations.

Scientists have extensively researched the causes of cancer, proposing the aforementioned theories regarding its origin. Among these, both intrinsic and extrinsic factors are considered crucial in driving cancer occurrence.

Intrinsic Factors: Mysterious Forces on the Cancer Stage

In the realm of cancer, intrinsic factors play a decisive role in determining fate. They play unique roles and hold significant positions closely tied to cancer development. Cellular identity is a core element, with each cell having a specific role. Epigenetics acts like a magician, manipulating DNA methylation, histone modifications, and non-coding RNA expression to activate or silence gene expression. Loss of DNA methylation, alterations in histone modifications, and abnormal expression of non-coding RNA can lead to cellular dysregulation. DNA mutations are another core element providing impetus for cancer development. Mutations in oncogenes activate certain genes, prompting cells to proliferate excessively, while mutations in tumor suppressor genes lead to loss of inhibitory functions. These intrinsic factors interact and collaborate in the development of cancer, weaving together a series of captivating dramas. When these factors undergo variations or contradictions, cells may deviate from the right path and evolve into cancerous cells.

Figure 3 Methylation remodeling of DNA, RNA, histones and non-histone proteins promotes the occurrence and development of tumors.

Figure 4 Changes in DNA methylation during aging and the methylation clock

External factors: Inseparable neighbors in the community

External factors play a crucial role in the development of cancer. The tumor microenvironment is a complex community comprising immune cells and tumor cells, whose interactions influence tumor growth, infiltration, and sensitivity to treatment. Certain microorganisms such as HPV and Helicobacter pylori infection are associated with cancer incidence (Figure 5), potentially promoting cancer development through chronic inflammation, DNA damage, and genetic mutations. Preventing infection and controlling microorganisms can reduce the risk of certain cancers. Mutagens such as chemical carcinogens, radiation, and certain drugs can cause DNA damage and mutations, increasing the risk of cancer. For example, chemicals in cigarette smoke are among the main mutagens for lung cancer. Understanding these external factors helps in better prevention and treatment of cancer.

Figure 5 Pathogens and cancer

The human body contains approximately 400 trillion cells of around 200 different types, organized within a complex three-dimensional matrix. Precise mechanisms suppress abnormal growth of malignant cells to prevent tumor formation. Understanding how tumor suppressive mechanisms are overcome, and how non-mutagenic pathways promote tumor growth, is of significant importance in cancer prevention and treatment. The occurrence of cancer results from the combined influence of intrinsic and extrinsic factors. Whether specific cells will develop into cancer at a particular time and place mainly depends on the interaction of these factors. Research reveals that aging and damaged tissues play crucial roles in cancer development, explaining why the risk of cancer increases with age. Although our understanding of the origins of cancer is still evolving, advances in research continually deepen our understanding of the process of cancer formation. This provides more possibilities for early diagnosis and treatment of cancer, contributing to more effective responses to global health challenges. Future research will continue to explore the interaction of intrinsic and extrinsic factors in order to better understand and control cancer.

Common Carcinogens: Warning Sounds of External Factors

1. With the Spring Festival approaching, don't trade health for joy

The Spring Festival is the most significant traditional festival in China, characterized by family reunions and gatherings. However, while enjoying delicious food and fine wine, we must also beware of some potential health hazards, the "invisible killers." Here are five types of traditional New Year products that you should handle with caution when purchasing and consuming to avoid compromising your health during the festive season.

Firstly, salted fish. Nitrosamines in cured foods are carcinogens that may lead to diseases such as nasopharyngeal cancer and esophageal cancer with prolonged consumption. During the Spring Festival, when consuming salted fish, it is advisable to consume them in moderation and preferably choose fresh fish.

Secondly, processed meat products like preserved pork and sausage. Studies have found that processed meat products contain high levels of nitrites and saturated fats, which may increase the risk of colorectal cancer with long-term consumption. Additionally, processed meat products may also contain excessive salt, which is detrimental to cardiovascular health. When indulging in preserved delicacies, consume them in moderation and accompany them with vegetables and fruits to balance nutritional intake.

Thirdly, betel nuts. Arecoline in betel nuts is classified as a potent carcinogen, and long-term chewing of betel nuts may increase the risk of oral and esophageal cancer. Moreover, the fibers and fine particles produced after chewing betel nuts can easily damage the mucous membranes of the mouth and esophagus, exacerbating the burden on the oral and digestive systems. During the Spring Festival, try to stay away from betel nuts and maintain healthy lifestyle habits.

Fourthly, moldy foods. Moldy foods may contain aflatoxins, which are potent carcinogenic substances that can damage the liver. Aflatoxins mainly exist in moldy grains, nuts, edible oils, and other foods. When purchasing and consuming these foods, inspect them carefully to avoid consuming moldy foods.

Lastly, excessive alcohol consumption. Alcohol is a well-known carcinogen, and prolonged heavy drinking can cause DNA damage, increasing the risk of cancer. During Spring Festival gatherings, drink alcohol in moderation, adhere to the principle of not urging or competing in drinking at the table, keep a clear mind, and enjoy a healthy and harmonious festival.

2. Family members living together

Family members living together for a long time tend to have similar lifestyles, and consequently, similar carcinogenic risk factors. For example, if a husband smokes, the wife may be exposed to passive smoking; if dining together, poor eating habits may harm both parties simultaneously; sharing the same living space exposes both individuals to environmental carcinogens. In addition, infections such as Helicobacter pylori and hepatitis B virus may also spread among family members living together, and these infections are closely associated with the occurrence of gastric cancer and liver cancer. If family members frequently consume high-fat, high-sugar, low-fiber foods, or lack sufficient fruits and vegetables, this may increase the risk of certain cancers. For instance, frequent consumption of barbecue or preserved foods in the family may increase the risk of gastric cancer or colorectal cancer.

3. Emotional factors

The family atmosphere also influences the occurrence of cancer. A lack of harmony in the family, mutual complaints between spouses, difficulty in coordinating with the elderly, and living in a state of tension and anxiety for a long time may increase the risk of cancer. Psychological negativity, feelings of frustration, and negative emotions affect family members and become another key factor in the onset of cancer. Prolonged exposure to high-stress levels may lead to a decline in immunity, increasing the risk of cancer. If family members often face stressors such as family conflicts or financial difficulties, this may have negative effects on the physical and mental health of family members.

The family is our warmest harbor and an important line of defense against cancer. In the family, we should focus on communication and care, establish a harmonious family atmosphere, pay attention to the health status of family members, promptly detect and address any physical discomfort. Additionally, we should emphasize health education for family members, helping them understand preventive measures against cancer, and work together for health.

The Spring Festival is a special occasion, carrying the Chinese people's longing for reunion and happiness. At this special moment, we should pay more attention to our health, cultivate good lifestyle and dietary habits, and bring more happiness and health to our families. In summary, health is the cornerstone of life, and we need to constantly monitor our physical condition, maintain good lifestyle and dietary habits. Only when our bodies are healthy can we better enjoy life, enjoy family and love, and lead a better life. And when we encounter diseases and challenges, the support of family and love will be our strongest backing. Let us work together to live for health and strive for happiness!

References

[1]Jassim A, Rahrmann EP, Simons BD, Gilbertson RJ. Cancers make their own luck: theories of cancer origins. Nat Rev Cancer. 2023 Oct;23(10):710-724.

[2]Liu R, Zhao E, Yu H, Yuan C, Abbas MN, Cui H. Methylation across the central dogma in health and diseases: new therapeutic strategies. Signal Transduct Target Ther. 2023 Aug 25;8(1):310.