Cancer is responsible for 25 percent of the deaths in America, which makes it the second leading cause of death in the U.S. To understand this disease, it is important to know that cancer is classically defined as an abnormal, unregulated growth of cells. This growth of abnormal, unregulated cells that produces a tumor is known as neoplasia and the tumor resulting from this is called a neoplasm. All tumors, or neoplasms, are not cancerous. Neoplasms can be non-cancerous, referred to as benign or cancerous, and also can be referred to as malignant. There are many differences between benign neoplasm and malignant neoplasms. Benign neoplasms contain characteristics of being slow growing, easily removed during surgery, not well vascularized, do not spread to surrounding tissues, and the cells resemble the tissue of origin. Malignant neoplasms are characterized by being rapidly growing, well vascularized, may spread to surrounding tissues, and have great variation in cell type which may, or may not, resemble the tissue of origin.
In order to properly understand the abnormal cell production that produces cancerous tumors, it is imperative that we understand the process of normal cell replication. In order for a cell to replicate properly, it must undergo two phases which are the S-phase in which DNA is synthesized and the chromosomes are duplicated and the M-phase, during which, mitosis occurs and the cell divides to form new cells. In addition, cells undergo preparatory intervals, called gaps, which prepares the cells for each phase of the replication cycles. The G1 gap prepares the cell for DNA synthesis, the G2 gap prepares the cell for mitosis (when a cell clones or duplicates itself by splitting into two separate but equal parts), and there is a resting state, GO gap, it sometimes occurs after a cell is replicated.
Cancer may be the result of genes undergoing abnormal changes due to mutation , deletion or amplification of the cell.
There are three genes, in particular, that are believed to play significant roles in cancer development. These genes are oncogenes, tumor suppression genes, and DNA repair genes. Proto-oncogenes are genes that promote normal cell growth and division by creating proteins to stimulate growth through signals from other cells. If a proto-oncogene mutates, it may over-stimulate cell growth and multiplication, which can lead to cancer. There are several circumstances under which proto-oncogenes may mutate. These circumstances may be the change in one, single gene, known as point mutation, chromosome rearrangement, gene amplification, and viral insertion. Oncogenes are responsible for several forms of cancer such as brain, breast, lung, ovarian, colon, pancreatic, as well as several others. Tumor suppression genes function to control over multiplication of cells to avoid cancer development. Mutations in tumor suppression genes cause the cells to ignore signals of cells over multiplying, which can lead to excessive cell growth and division, thus, the formation of cancer may occur. Mutations of tumor suppression genes are responsible for several forms of cancer such as pancreatic, pheochromocytoma, bone, bladder, Wilm’s tumor of the kidney, as well as several others. DNA repair genes are responsible for the accurate transfer of genetic information between cells during the multiplication process. Mutations, in this type of cells, can lead to more frequent mutations and chromosomal abnormalities, which can lead to cancer development. DNA repair genes are responsible for Bloom’s syndrome, ataxia-telangiectasia, and hereditary nonpolyposis colon cancer.
Carcinogens are environmental factors that can influence genetic changes and consequently lead to cancer development. Carcinogens can be in various forms such as chemical, physical, viral, or hormonal.
Cigarette smoke, food additives, and pesticides are examples of chemical carcinogens. Radiation, including ultraviolet light, is an example of a physical carcinogen. An example of a hormonal carcinogen would be an over exposure to estrogens. The Human-papilloma virus, the Epstein-Barr virus, and the hepatitis B virus are all known viral carcinogens. The development of cancer due to exposure to a carcinogen is known as carcinogenesis. Tumor growth is very dependent on nutrients in order for the tumor to expand, thus, adequate blood flow, to and within the tumor, is crucial for this to occur.
The process of establishing adequate blood flow and blood vessel growth is known as angiogenesis. Angiogenesis occurs when epithelial cells of normal blood vessels multiply and invade the surrounding tissue, thus, creating an adequate blood supply to the tumor. For the adult population, angiogenesis, usually, only occurs during wound repair or childbirth. For individuals with cancer, epithelial cells multiply in an abnormal fashion in response to a variety of factors.
It is assumed that the development of cancer begins with the mutation of a single cell, however, most tumors are not detected until they are approximately one gram in weight, about the weight of a marble. In order to achieve a tumor weight of one gram, a cell must multiply in excess of thirty times. In order for a tumor to grow from one gram to one kilogram, the tumor must multiply only ten times. The maximum size a tumor can reach, and the human still be surviving, is two kilograms, thus, most cancerous tumors are fairly advanced by the time they are diagnosed. The rate in which tumors grow varies greatly with the types of cancer. For example, testicular cancer has very rapid tumor growth, whereas, prostate cancer growth is relatively slow. The growth fraction is defined as the number of cells a malignant tumor is actively producing. The greater the number of cells that are being produced, the faster the tumor is going to grow. Treatment options are based, largely, upon the growth fraction of the tumor because fast growing tumors, such as testicular cancer, may be more susceptible to therapies such as radiation and chemotherapy than slower growing tumors.
The majority of cancer related deaths occur due to a phenomenon called metastasis. Metastasis is simply the manner in which a cancer spreads from its original site to invade other parts of the body. Metastasis is initiated when cancer cells invade neighboring tissue and is incorporated in the lymphatic vessels or blood vessels. Once cancer cells have established location in the vessels, the process of tumor growth begins all over again at the new location. It should be noted that when a cancer spreads, the resulting tumor has the same type of cells as the original tumor. Even with this vast knowledge and understanding, researchers have been unable to prevent the disease from being the second leading cause of death in America.
For example, if breast cancer spreads to the liver, there tumor of the liver is actually comprised of breast cells. It should also be noted that metastatic cancers have a wide variety of cell types and the more varied the cell population, the more difficult the cancer is to treat.
There are in excess of 100 types of cancer, among which, symptoms, treatment regimens, and disease progression may vary greatly. Hematologic malignancies are cancers of the blood forming cells such as leukemia and lymphoma. Leukemia that arises in the bone marrow, is characterized by immature white blood cells and decreased immune function, which results in anemia, recurrent infections and uncontrolled bleeding. Lymphomas affect the cells of the lymph system and there are a variety of lymphomas. Non-Hodgkin’s lymphoma is associated with enlarged lymph nodes, weight loss, fatigue, and fever, whereas, Hodgkin’s lymphoma is characterized by the presence of Reed-Sternburg cells. Solid tumors such as sarcomas, carcinomas, adenocarcinomas and blastomas, are named according to their tissue of origin. It should be noted that carcinomas account for approximately 80 percent of all diagnosed cancers. It should be emphasized that cancers occur differently in men and women.
In addition, the prevalence of certain types of cancers, among men and women, does not directly correlated with death rates of cancers. Note that prostate cancer is most prevalent among males, however, lung cancer is the most deadly form among men. Conversely, breast cancer is the most prevalent form of cancer among women, whereas, lung cancer is also the most deadly form.
Although cancer is the second leading cause of death among Americans, in recent years, we have seen a steady decline in mortality rates associated with several forms of cancer. The recent decrease in mortality rates can be directly linked to extensive epidemiologic research that has identified potential carcinogens and suggest numerous ways for individuals to prevent the development of cancer, simply because scientists have a better understanding of the disease.
By Robert E. Shifko
Contributions by: D. Chandler