Cancer
Cancer refers to a group of more than 100 different diseases characterized by cellular genetic changes such as DNA mutations and damage that cause abnormal cell growth and development. Malignant cells have two defining characteristics: first, the cells no longer divide and differentiate normally; they can invade surrounding tissues. Secondly, the malignant cells are capable of travel to and growth in distant sites within the body. In the United States, greater than 1.6 million new cases of cancer are expected in 2016; it is the number one cause of death in people younger than age 85, and accounts for more than half a million deaths each year (NIH/NCI, https://www.cancer.gov/about-cancer/understanding/statistics).
CAUSES
Cancer risk factors may include those that can be controlled, such as exposure to substances and certain behaviors, and factors that cannot be controlled, such as age and family history.
Current evidence suggests that cancer develops from either inherited genetic changes or acquired genetic changes resulting from, for example, the exposure to carcinogens (cancer causing agents), such as asbestos, mineral oils, tobacco smoke, and radiation from the sun. Furthermore, additional genetic changes may continue to develop in cells as a result of the cancer itself.
Numerous genetic changes and genes have been identified that may cause cancer or increase one’s risk of developing cancer. According to the NCI (https://www.cancer.gov/about-cancer/understanding/what-is-cancer#related-diseases), genetic changes, inherited or acquired, may occur in three major types of genes — proto-oncogenes, tumor suppressor genes, and DNA repair genes. If unchanged, these genes would normally help to halt or prevent the development of cancer.
Proto-oncogenes may develop changes that can cause them to become oncogenes that in turn promote abnormal growth and development in cells that would normally be halted. Tumor suppressor genes may be altered so that cells continue to divide and multiply in an uncontrolled manner that should normally be halted by unaltered tumor suppressor genes. And finally, mutations or changes in DNA repair genes may inhibit DNA repair, and thus, the DNA damage continues and additional mutations develop in other genes allowing or promoting cancer cell growth and development.
Oncogenes provide growth-promoting signals, thereby causing one or more characteristics of cancer cells when overexpressed or mutated.
Proto-oncogenes are genes that can be converted to oncogenes by transforming cells or contributing to tumor formation. Tumor suppressor genes are growth-suppressing genes that inhibit tumor development.
Both types of these cancer-related genes can be inherited or acquired. Common causes of acquired genetic damage are viruses, radiation, environmental and dietary carcinogens, and hormones. Other factors that interact to increase a person’s likelihood of developing cancer are age, genetics, nutritional status, hormonal balance, and response to stress.
RISK FACTORS
Many cancers are associated with exposure to specific environmental (air pollution, tobacco and alcohol, occupation, and radiation) and lifestyle factors (sexual practices and diet) that may increase one’s risk to developing cancer. Accumulating data suggest that some of these factors initiate carcinogenesis, others act as promoters, and some both initiate and promote the disease process. In addition, age and inherited genetics can also determine one’s risk of cancer.
Carcinogens
The following section contains a discussion and description of some more common cancer causing substances (carcinogens).
Air Pollution
Environmental factors such as air pollution have been linked to the development of cancer, particularly lung cancer. Many chemicals and other materials used in manufacturing and everyday life contribute to air pollution and are therefore carcinogens, such as arsenic, benzene, hydrocarbons, polyvinyl chlorides, and other industrial emissions as well as motor vehicle exhaust. Other indoor air pollution carcinogens include radon gas, and smoke from tobacco products and burning of cooking fuel. Between 2005 and 2009, there were over 7,000 lung cancer deaths each year due to secondhand smoke exposure (U.S. Department of Health and Human Services, 2014).
Tobacco and Alcohol
Tobacco and many of the chemicals present in tobacco smoke are carcinogenic and responsible for DNA damage in cells associated with cancer. Smoking is responsible for 80% of all lung cancer deaths. The use of tobacco, smoked or smokeless, causes cancer. The risk of lung cancer from cigarette smoking correlates directly with the duration of smoking and the number of cigarettes smoked per day. Research also shows that a person who stops smoking decreases his/her risk of lung cancer.
Although the risk of lung cancer is not strongly associated with pipe and cigar smoking as it is with cigarette smoking, there is evidence that pipe and cigar smoking is associated with oral and other cancers. Smokeless tobacco contains many carcinogens and nicotine and can cause oral and pancreatic
cancers (U.S. Department of Health and Human Services, 2014). Inhalation of secondhand smoke, or passive smoking, by nonsmokers also increases the risk of lung and other cancers. The risk of developing an alcohol-related cancer increases with the amount of alcohol consumed regularly over time. Heavy alcohol consumption is an independent risk factor and primary cause of hepatocellular carcinoma. Head and neck, esophageal, breast, and colorectal cancers are also associated with alcohol consumption. Alcohol may increase the risk of cancer through several different mechanisms including those mechanisms that can damage DNA and proteins, and it can impair the absorption and breakdown of nutrients associated with cancer risk. The fermentation and production process for alcoholic beverages may also introduce known carcinogens as a contaminant into the alcoholic beverages. Heavy use of alcohol and cigarette smoking multiplicatively increases the incidence of cancers of the mouth, larynx, pharynx, and esophagus.
cancers (U.S. Department of Health and Human Services, 2014). Inhalation of secondhand smoke, or passive smoking, by nonsmokers also increases the risk of lung and other cancers. The risk of developing an alcohol-related cancer increases with the amount of alcohol consumed regularly over time. Heavy alcohol consumption is an independent risk factor and primary cause of hepatocellular carcinoma. Head and neck, esophageal, breast, and colorectal cancers are also associated with alcohol consumption. Alcohol may increase the risk of cancer through several different mechanisms including those mechanisms that can damage DNA and proteins, and it can impair the absorption and breakdown of nutrients associated with cancer risk. The fermentation and production process for alcoholic beverages may also introduce known carcinogens as a contaminant into the alcoholic beverages. Heavy use of alcohol and cigarette smoking multiplicatively increases the incidence of cancers of the mouth, larynx, pharynx, and esophagus.
Occupation
Certain occupations that expose workers to specific substances increase the risk of cancer. For example, persons exposed to asbestos are at risk for a specific type of lung cancer, called mesothelioma. Asbestos also may act as a promoter for other carcinogens. Workers involved in the production of dyes, rubber, paint, and beta-naphthylamine are at increased risk for bladder cancer.
Radiation
Exposure to radiation is a known risk for cancer. Ionizing radiation from X-rays and gamma rays can cause cancer by damaging and changing the cell’s DNA. Ultraviolet (UV) radiation, a lower energy radiation than X-rays or gamma rays, mainly causes skin cancer by damaging the DNA in skin cells. Radiation comes from natural sources, such as radon gas and the sun, or can come from man-made sources, such as those for tanning beds, nuclear energy, and imaging studies. The risk of cancer increases with the amount of radiation exposure.
UV sunlight is a direct cause of basal and squamous cell cancers of the skin. The amount and type of exposure to UV radiation correlates with the type of skin cancer that develops. For example, cumulative exposure to UV sunlight is associated with basal and squamous cell skin cancer, and severe episodes of burning and blistering at a young age are associated with melanoma. Ionizing radiation (such as X-rays and gamma rays) is associated with acute leukemia; thyroid, breast, lung, stomach, colon, and urinary tract cancers; as well as multiple myeloma. Low doses of radiation can cause DNA mutations and chromosomal abnormalities, and large doses can inhibit cell division. Ionizing radiation can also enhance the effects of genetic abnormalities. Other compounding variables include the part and percentage of the body exposed, the person’s age, hormonal balance, use of prescription drugs, and preexisting or concurrent conditions.
Human Papillomaviruses
Human papillomaviruses (HPVs) are a group of more than 200 related viruses. More than 40 types of HPVs can be transmitted with direct sexual contact from skin and mucous membranes of the infected person to the sexual partner through vaginal, oral, and anal sexual practices. High-risk HPVs are responsible for causing several types of cancer with two types, 16 and 18, responsible for the majority of the HPV-related cancers. HPV is the most common cause of abnormal Papanicolaou (Pap) tests, and cervical dysplasia is a direct precursor to squamous cell carcinoma of the cervix, both of which have been linked to HPV. HPV types 16 and 18 cause 70% of all cervical cancers. More than half of all oral cancers are linked to HPV type 16, and most anal cancers are caused by HPV type 16. Three vaccines have been approved by the Food and Drug Administration (FDA) to prevent HPV infection before sexual activity. The vaccines do not treat HPV infections or related diseases once established.
Dietary Factors
According to the National Cancer Institute (NCI), many studies have been conducted to evaluate the relationship of dietary nutrients or other food-related factors with cancer in humans. Studies to date have not yet been able to show a cause and effect relationship with dietary components that may either cause or prevent cancer. Large epidemiological studies have shown only a correlation or association of dietary components and cancer risk, but not a causal relationship. It is possible or likely that many other factors other than the dietary-related ones in these studies may be responsible for the differences found in the associations of dietary factors and cancer risk.
Age
Age is a major determinant in the development of cancer. The longer men and women live, the more likely they are to develop the disease. For example, because of the long natural history of common cancers, prostate cancer may take up to 60 years to become invasive, while colon cancer may take as long as 40 years to develop into an invasive stage. Possible explanations for the increased incidence of cancer with advancing age include:
altered hormonal levels, which may stimulate cancer
ineffective immunosurveillance, which fails to recognize and destroy abnormal cells
prolonged exposure to carcinogenic agents, which is more likely to produce neoplastic transformation
inherent physiologic changes and functional impairments, which decrease the body’s ability to tolerate and survive stress.
Genetics
Genes, through the proteins they encode, are the chemical messages of heredity. Located at specific locations on the 46 chromosomes within the cell’s nucleus, genes transmit specific hereditary traits.
Most cancers develop from a complex interplay among multiple genes and between genes and internal or external environmental factors. Phenomenal progress has been made in the fields of cancer genetics and cytogenetics that has established specific chromosomal changes as diagnostic and prognostic factors in acute and chronic leukemias, as diagnostic factors in various solid tumors, and as indicators for the localization and characterization of genes responsible for tumor development.
Moreover, in the past 25 years, research has identified and characterized many of the genetic alterations that lead to tumor transformation at the chromosomal and molecular cell level. The Human Genome Project, started in 1988 to identify the entire sequence of human DNA, has helped to increase knowledge about genetics and cancer carcinogenesis. The Philadelphia (Ph) chromosome was the first identified chromosomal anomaly caused by translocation implicated
in a human disease (chronic myelocytic leukemia [CML]). However, it’s important to note that not all mutated genes always lead to disease.
in a human disease (chronic myelocytic leukemia [CML]). However, it’s important to note that not all mutated genes always lead to disease.
As previously discussed, two sets of genes, oncogenes and tumor suppressor genes, participate in the transformation of a normal cell into a malignant cell; however, because multiple, successive changes and distinct cellular genes are required to complete the entire process, the human cell rarely sustains the necessary number of changes needed for tumor transformation. Gene mutations are either inherited from a parent (hereditary or germline mutation) or acquired (somatic mutation). Inherited gene mutations may account for approximately 5% to 10% of all cancers. Additionally researchers have identified mutations in genes that are associated with greater than 50 malignant syndromes. A cancer syndrome is not a definitive cancer, but rather a disorder that may put an individual at a higher risk for developing a specific cancer (https://www.cancer.gov/about-cancer/causes-prevention/genetics). Acquired mutations are changes in DNA that develop throughout a person’s lifetime. Carcinogenic agents, such as radiation or toxins, commonly are able to damage cellular genes, which are present in the cancer cell genome, thereby triggering cancer development.
Hereditary Genes
The list of genetic mutations listed below represents the more commonly inherited cancer syndromes:
the adenomatous polyposis coli (APC) suppressor gene, which is altered by somatic mutations in colonic epithelial cells, permitting the outgrowth of early colonic polyps
familial adenomatous polyposis (FAP) or APC, which acts as an autosomal dominant inherited condition in which hundreds of potentially cancerous polyps develop in the colon and rectum
familial cutaneous malignant melanoma gene, on the distal short arm of chromosome 1
expression of the N-myc oncogene in neuroblastoma, with amplification of this oncogene associated with rapid disease progression in children
germline mutation of the P53 gene, which is mapped to the short arm of chromosome 17 and is associated with Li-Fraumeni syndrome, an extremely rare familial cancer syndrome that increases susceptibility to breast cancer, soft tissue sarcomas, brain tumors, bone cancer, leukemia, and adrenocortical carcinoma
human epidermal growth factor receptor-2 (HER-2)/neu protooncogene, which is involved in regulation of normal cell growth. Gene amplification or HER-2/neu overexpression, which occurs in 25% to 30% of human breast cancers and to varying degrees in other tumor types, produces activated HER-2/neu receptors and stimulates cell growth. Tumors positive for the HER-2/neu gene are associated with poor clinical outcomes, shortened disease-free survival, more rapid cancer progression, and poor response to historically standard clinical interventions.
retinoblastoma — The RB1 Gene. Retinoblastoma may be hereditary or nonhereditary and usually occurs in children less than 5 years old.
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