number 15 Done by Ali Yaghi Corrected by Waseem Alhaj Doctor مها شوماف 1 P a g e
Epidemiology Epidemiology is the study of the incidence of a disease. It can give us information about the possible causes of the disease, the incidence of different types of tumors and the predisposing factors. Note: The information we know now is from the observation of tumors. In any country, there is a center called cancer registry center, this center collects the new cases of cancer diagnosed in different sites in hospitals and analyses the data in order to come up with some information and it gives us a clue about the common cancers in any area. Also it can give us a clue about the mortality rates caused by cancer and patient survival. Note: This is helpful if we are thinking for example to make a campaign about cancer, we must choose a common cancer (such as breast cancer). Note: cancer registry center makes a statistic every few years (not every year). *In females the most common type of cancer is breast cancer followed by lung cancer then colon cancer. * In Males the most common type of cancer is prostate cancer followed by lung cancer then colon cancer. - - - - - - - - - - - - Note: the incidences of cancer differ from one year to another because of the efforts that were done to lower some types of cancers. 1- environmental factors 2- age 3- genetic factors Factors that affect the incidence of cancer: Environmental factors: When we find that a population shares some common factors (such as working in some industries) that can result in developing one type of cancer more than the rest of the population not subjected to the same factors, this should raise the suspicion that they are subjected to an antigen that results in cancer which comes from these specific factors. Examples: 1- the cancer of stomach is common in far Asians (Japanese), when they compared the native Japanese with the Japanese immigrants to USA, they found out that the first generation had high stomach cancer incidence(same as native 2 P a g e
Japanese).However, in the second and third generations, the incidences started to drop as low as it is in the USA. This raised the possibility that the stomach cancer is affected by a certain type of food (Japanese eat a lot of smoked fish and meat, and the process of smoking fish increases the nitrosamines). The first generation sustained the food habits and this explains the high stomach cancer incidence in them. 2- Colon cancer is a western type of cancer (high incidence of colon cancer in west in comparison with Africans). It is also related to the type of food consumed. 3- Breast cancer is also seen in western countries in a higher incidence than in Asians. It is related to the number of pregnancies, lactation habits, age of menopause, age of menarche and hormonal status. 4- Liver cancer in African countries usually occurs in young age groups because of the exposure to carcinogens from the alpha toxin which is produced by a fungus that grows on food so the exposure to carcinogens occurs early in life, but in western countries it occurs in elderly as it is related to alcoholism and liver cirrhosis. This table shows you the number of carcinogens that are present in our environment and we are exposed to, and the types of cancers that can result from them. 3 P a g e
1- Arsenic and arsenic compounds associated with lung and skin cancer and hematoma. 2- Asbestos is involved in rare cancer (mesothelioma). 3- Benzene containing materials are carcinogens especially lymphoma and acute amyloid leukemia. 4- Heavy metals (used as latent adhesive materials in dyes and paints) are involved in lung cancers. 5- Radio-active gas for example radon which is present in air. The level of radon should be measured and be very low in order ensure safety of living in that specific area. The second factor that affects the incidence of cancer is age Most cancers happen in middle age groups because the exposure to cancerous substances increases (every day we are exposed to them) and cell mutation increases, also the immune surveillance and competency decreases. When the immune system is inefficient, the abnormal cells can escape the immune detection and can acquire more mutations. Most cancers that affect young people are leukemia, lymphoma, soft tissue sarcoma, osteosarcoma and central nervous system tumors. The most common age of cancer patients is 45 75(in the book it is 55-75), so when a young patient is diagnosed with some type of cancer that affects the elderly, you should suspect that hereditary factors play a role. Note: 10% of all deaths among children younger than 15 of age are because of cancer. 4 P a g e
The third factor that affects the incidence of cancer is genetic factors 1- Retinoblastoma - which is caused by mutations in retinoblastoma gene (tumor suppressant gene) it is the first gene studied. 2- P53 gene in li-fraumeni syndrome that is characterized by family members who have different types of cancers 3- P16 - melanoma, 4- APC gene this gene mutation causes development of polyps in GI tract. Note: People with half mutated APC gene will eventually develop a cancer in early age. 5- BRCA 1 -- BRCA2 genes mutations related to breast cancer and ovarian tum. The incidence of developing cancer is very high if the tow muted genes are present. Note: Some women choose to have mastectomy in order to bypass the development of breast cancer because they have BRCA 1- BRCA2 gene mutation. 6- Neurofibromatosis is related to NF1- NF2 gene mutations. Note: people diagnosed with benign tumor originate from myelin sheath (neurofibromatosis) will eventually have malignant nerve sheath tumors. 7- MEN-1, RET genes result in a multiple endocrine tumor (benign and tumor) such as thyroid cancer, adrenal cancer and pituitary cancer. Side note: If a person is diagnosed with cancer at an old age it doesn't mean that he doesn't have a mutated gene, it just means that the mutation has occurred at an old age. 5 P a g e
There is also a type of cancer related to inefficiency in DNA repair enzymes. One of these diseases is xeroderma pigmentoma. DNA gets damaged all the time, however because we have the repair system (group of enzymes their function is to repair damage and compensate the loss of DNA) the DNA stays normal and we don t get cancer. Any mutation in the repair genes causes mutation in these enzymes, so a mutated person cannot be exposed to sun because ultraviolet radiation causes DNA damage, and these people develop skin cancer very early and it is recurrent, meaning that every time we remove it, it returns again. Note: classical skin cancer occurs in elderly. Familial cancer is caused by genes that are not well identified yet. However, there is a well documented increase in development of cancer in certain families, but not necessarily the same type of cancer. This is well known in breast cancer. Breast cancer can be familial and it could be because of BRCA genes and other non identified genes. Ovarian cancer also is caused by the same genes. Pancreatic cancer can be inherited; there is a gene of pancreatic cancer and colon cancer. Note: 5% of the tumors start as an inherited factor, but always think of cancer as an interaction between the environment and the genetic factor. Some genes that enhance cell transformation can be inherited (that s why these people are more liable to get cancer). But inheritance of mutated genes is not always associated with development of cancer, it should be exposed to some environmental factors to induce it and activate it, otherwise cancer will not develop. For example, if we have twins that have the same genetic component one diagnosed with cancer and the other is not, it is because of the environmental factor. What is the importance of knowing that this is an inherited cancer? To warn other family members and to encourage them to screen and detect any precancerous signs in order to prevent the development of cancer. What are the features of inherited cancer? Inherited cancers are multiple (affects many organs). Ex: it affects the two kidneys not only one (it is called bilateral). Clinical correlation: if a young patient visits the clinic and discovered a bilateral breast cancer, we should suspect an inherited cancer. Also if a patient is diagnosed with multiple breast masses, we should check the other breast because there is a possibility to have another tumour in the other breast. Note: colon cancer occurs below 30 years old. 6 P a g e
Preneoplastic conditions: These are not neoplastic, but these conditions are prior to cancer, you should treat these conditions very well in order to decrease the risk of developing cancer. Chronic irritation of cells increases the likelihood of cancer development. This is because irritated cells are always damaged and always gets stimulated to enter the cell cycle and get repaired, so the DNA of it is in progressive unwinding and duplication steps, so the chance of mutating a gene is higher. Preneoplastic conditions: chronic wound, chronic ulcer 1- Endometrial hyperplasia (caused by excessive estrogen secretion) if the effect of estrogen is not "protected" by progesterone it can cause endometrial sarcoma, that's why patients are treated with estrogen and progesterone. 2- Chronic atrophy gastritis is caused by helicobacter pylori bacteria, it is an inflammatory condition. However, the chronic inflammation is associated with the development of cancer in the stomach (adenocarcinoma and lymphoma). That s why H. pylori should be treated effectively. 3- Inflammatory bowel disease such as ulcerative colitis. It is recognized by severe and continuous damage in the mucosa by the inflammation. After 10 years the risk of developing malignancy increases so we should follow up the patient by endoscopies in order to detect any change that is precancerous. And when it is severely chronic, the treatment is resection in order to prevent the development of cancer. 4- Leukoplakia which is thickening in the oral mucosa and white patches in the smokers and people who chew some plant material. These people have increased risk of developing oral mucosa 5- Villous adenoma in the colon which is a benign tumor of colonic mucosa. However, it has an increasing risk of malignancy. Therefore, if the patient is diagnosed with villous adenoma, the patient must have close up care and must have endoscopy every 6 months especially if he is in the age of malignancy. Note: sometimes the cancer starts within the villous adenoma. 7 P a g e
Differentiation between benign and malignant The differentiation is the similarity to the normal tissue (our normal human cells are the most differentiated type of cells). The similarity of the tumour cells to that of the normal ones is the differentiation. If it shows 100% similarity, it is a benign tumour. However for malignant tumour, it is not 100% similar to the normal cells. Therefore the differentiation of malignant tumour is graded. Note: The most important way is the microscopic appearance, so it is important to take a biopsy. Grades of malignant tumour: 1- Well differentiated: similarity is very high. number 1 2- Moderate differentiated: some differentiation (adenocarcinoma tumor cells can form glands but not similar to normal ones) 3- Poorly differentiated: there is no similarity between normal cells and tumor (difficult to identify the origin cell). number 4 Note: the extreme of non-differentiation is anaplasia. Anaplasia means that tumour is composed of cells that are very bizarre, large in size, have large nuclei, and are abnormal. Importance of anaplasia: when you know that the patient has an anaplastic tumour you should expect that the tumour will be aggressive (so it is poorly differentiated). 8 P a g e