Module 4.1 Cancer Flashcards
1
Q
What are oncogenes?
A
- They are mutant genes that in their normal nonmutant state direct synthesis of proteins (growth factors) that positively regulate (accelerate) proliferation (growth factors).
2
Q
What are tumor suppressor genes?
A
- They are genes that in their normal state negatively regulate (halt) proliferation, aka anti-oncogenes, and they prevent mutations.
- They normally slow the cell cycle, inhibit proliferation resulting from growth signals, or stop cell division when cells are damaged.
3
Q
What is the function of caretaker genes?
A
- They are genes that are responsible for maintaining genomic integrity
- These genes encode proteins that are involved in repairing damaged DNA, such as occurs with errors in DNA replication, mutations caused by UV or ionizing radiation, mutations caused by chemicals, and drugs
4
Q
What happens when oncogenes/proto-oncogenes are mutated?
A
Results in overexpression or amplification of growth factors leading to a gain of function
5
Q
What happens when tumor suppressor genes are mutated?
A
- For the function of a tumor suppressor gene to be lost both chromosomal copies of the gene must be inactivated
- The 1st allele of is usually inactivated by point mutations
- The 2nd allele is either epigenetically silenced or a piece of the chromosome is simply lost
- If the tumor suppressor gene is mutated it results in unchecked cell division,
6
Q
What is the normal function of the TP53 gene?
A
- When the DNA in a cell becomes damaged by agents such as toxic chemicals, radiation, or ultraviolet (UV) rays from sunlight, this protein plays a critical role in determining whether the DNA will be repaired or the damaged cell will self-destruct (apoptosis).
- If the DNA can be repaired, p53 activates other genes to fix the damage. If the DNA cannot be repaired, this protein prevents the cell from dividing and signals it to undergo apoptosis.
- By stopping cells with mutated or damaged DNA from dividing, p53 helps prevent the development of tumors & prevents uncontrolled cellular growth (it is a tumor suppressor)
- This gene is found in the nucleus of the cells throughout the body
7
Q
What is telomerase and describe its role of telomerase in cancer development
A
- Telomeres are protective caps on each chromosome and are held in place by telomerase.
- Telomeres become smaller and smaller with each cell division. Cancer cells can restore telomeres by increasing telomerase, leading to continued division
- Body cells are not immortal and can divide only a limited number of times.
8
Q
What are tumor markers ?
A
- Substances produced by cancer cells or that are found on plasma cell membranes, in the blood, CSF, or urine and can be hormones, enzymes, genes, antigens, and antibodies.
- These markers can be increased by noncancerous as well as cancerous conditions; therefore, these are not used to diagnose cancer.
9
Q
What are tumor markers used for?
A
- Screen and identify individuals at high risk for cancer
- To help diagnose the specific type of tumor in individuals with clinical manifestations relating to their tumor.
- To follow the clinical course of a tumor
10
Q
How does HPV cause cancer?
A
- The virus infects the basal skin cells and causes warts leading to cervical cancer in some people
- HPV is more likely to cause cancer in people with prolonged infection of the virus (10+ years), during which the viral DNA becomes integrated into the genomic DNA of the infected basal cells of the cervix and directs the persistent production of viral oncogenes
11
Q
How does EBV (Epstein-Barr) cause cancer?
A
- The virus infects B lymphocytes and stimulates their proliferation
- The infection usually remains latent throughout the individual’s life
- In individuals who are immunosuppressed (HIV/immunosuppresents), persistent infection can lead to the development of B-cell lymphomas.
12
Q
How does HTLV-1 (Human T-cell lymphotropic virus type 1) cause cancer?
A
- It is an oncogenetic retrovirus linked to the development of Adult T-cell leukemia and lymphoma
- It is transmitted vertically - Inherited by children from infected parents
- And horizontally - Breastfeeding, sex, blood transfusions, and exposure to infected needles
13
Q
Explain how chronic inflammation can lead to cancer
A
- Inflammatory cells, including neutrophils, lymphocytes, and macrophages, migrate to the site of injury and release cytokines, growth factors, and survival factors that stimulate local cell proliferation and new blood vessel growth to promote wound healing by tissue remodeling
- These factors combine in chronic inflammation to promote continued proliferation
- Inflammatory cells release ROS and other reactive molecules that promote mutations and block the cellular response to DNA damage
- Persistent mutations and DNA damage lead to malignant cell types leading to cancer
14
Q
What is tumor necrosis factor (TNF) and how does it promote cancer?
A
- Tumor necrosis factor (TNF) is a multifunctional cytokine (double-edged sword) that plays important role in diverse cellular events such as cell survival, proliferation, differentiation, and death
- TNF is secreted by inflammatory cells, which may be involved in inflammation-associated carcinogenesis
-
TNF stimulates cancer cells’ growth, proliferation, invasion and metastasis, and tumor angiogenesis
- BUT it also can stimulate the cancer cell’s death if the cancer cell is not resistant to TNF-induced cytotoxicity, resulting in tumor promotion.
15
Q
Describe Paraneoplastic Syndrome and what causes it
A
- Symptom complexes that are triggered by cancer by are not caused by direct local effects of the tumor mass
- They are commonly caused by biological substances released from the tumor (hormones) or by an immune response triggered by the tumor
- These symptoms may be the earliest symptom of an unknown cancer and can be serious, irreversible, and life-threathening
16
Q
What is the normal function of the BRAC 1 & 2 gene?
A
- BRCA1 is located on the long arm of chromosome 17.
- BRCA2 is on the long arm of chromosome 13.
- These genes when normal produce tumor suppressor proteins that prevent abnormal cell growth & are involved in repairing damaged DNA
17
Q
What happens when the BRCA 1 & 2 genes have mutations?
A
- Gene mutations lead to the production of an abnormally short version of the BRCA1 or BRCA2 protein or prevent any protein from being made from one copy of the gene.
- Less of this protein is available to help repair damaged DNA or fix mutations that occur in other genes → they can trigger cells to grow and divide uncontrollably to form a tumor.
- A deletion in either gene increases a woman’s risk of developing breast / ovarian cancer
- 50-60% of women with a mutation of either gene develop breast cancer by age 70
18
Q
What causes breast cancer?
A
- Breast cancer is thought to result from mutations during differentiation of stem cells into mature epithelial cells.
- Genetic factors and/or environmental factors produce the mutation. Growth factors, e.g. estrogen and progesterone, increase growth of premalignant to malignant cells.
- Modification of specific oncogenes or loss of suppressor genes allows disease to progress
20
Q
What is Ductal carcinoma in situ (DCIS)?
A
- The most common type of in situ cancer
- DCIS may develop in several areas of a duct, appearing as a cluster of calcifications or white flecks on a mammogram.
21
Q
What is Infiltrating ductal carcinoma (IDC)?
A
- The most common invasive breast cancer, approx. 79% of all breast cancer
- This is a ductal carcinoma that has a broken through the duct wall to invade the fatty tissue of the breast.
- IDC appears as a mass on a mammogram or may be felt as a palpable lump during a breast exam.
- May cause nipple discharge
22
Q
What is Infiltrating lobular carcinoma?
A
Breast cancer that occurs when malignant cells grow through the walls of a lobule. It can spread to other locations via lymphatic channels of the blood stream.
23
Q
What is Inflammatory breast cancer?
A
- It is an unusual but aggressive breast cancer
- It begins with breast swelling, redness and warmth produced by blockage of lymphatic channels by cancer cells.
- It can be confused with mastitis, until it fails to respond to antibiotic treatment.
24
Q
What is Paget’s disease of the breast?
A
- It is a rare ductal carcinoma beginning in the ducts near the nipple.
- It causes itching, redness and flaking of the nipples & sometimes the affected area bleeds.
25
Q
What are some clinical manifestations of breast cancer?
A
- local pain
- dimpling of skin
- nipple retraction
- skin retraction
- edema
- pitting of the skin
- reddened, local tenderness, and warmth
- dilated blood vessels
- nipple discharge
- ulceration
- hemorrhage
- edema of the arm
26
Q
Describe how cancer is staged?
A
Stages:
- Cancer is confined to its organ of origin
- Locally invasive
- Regional structures
- Distant sites
27
Q
What are the 5 types of lung cancer?
A
- Squamous cell carcinoma
- Oat Cell carcinoma (Small Cell Lung Cancer)
- Adenocarcinoma
- Large cell carcinoma
- Metastatic Lesions
29
Q
What is Oat Cell carcinoma (Small Cell Lung Cancer), what are the signs & symptoms of it, and how do you treat it?
A
- One of the more common lung tumors (2-25%)
- Strongest correlation with cigarette smoking
- Tends to begin in the medial portion of the lung. This makes it difficult to detect upon chest x-ray.
- Aggressive, metastasize early, poor prognosis
Signs & symptoms:
- Often asymptomatic until obstruction develops.
- Then symptoms of cough (or change in cough), pain, shortness of breath, hemoptysis, recurrent infections, hoarseness, dysphagia, weakness, weightloss, anorexia, and anemia occur.
Treatment:
- Chemo & radiation
30
Q
What is adenocarcioma?
A
- Most common type of lung cancer, accounting for approximately 40% of cases.
- Often located peripherally and may be seen easily on chest x-ray.
- Metastasizes rapidly.
- Clinically manifests with pleural effusions
- treated surgically, chemotherapy adjunctive
31
Q
What is large cell carcinoma?
A
- Accounts for about 10% of cases.
- Similar to adenocarcinoma, but with cells that appear differently microscopically.
- Frequently metastasizes and has a poor survival rate.
- Neither radiation therapy nor chemo increase survival
32
Q
What are some characteristics of prostate cancer?
A
- Most common cause of cancer in US men and second leading cause of death in males over age 55
- 95% of prostate cancers are adenocarcinomas. In approximately 4% of men with prostate cancer, the neoplasm has transitional cell morphology and is thought to arise from the urothelial lining of the prostatic urethra.
- In rare cases, the tumor has a neuroendocrine morphology; in such instances, the neoplasm is believed to have arisen from the neuroendocrine stem cells that are normally present in the prostate or from aberrant differentiation programs during cell transformation.
- 75% of prostate cancers arise in the peripheral zone, 15-20% arises in the central zone, and 10-15% arises in the transition zone.
33
Q
What are the clinical manifestations associated with prostate cancer?
A
With PSA screening:
- urinary frequency (38%)
- decreased urine stream (23%)
- urinary urgency (10%)
- hematuria (1.4%)
- Asymptomatic (47%)
However, none of these symptoms are unique to prostate cancer & each can arise from various other ailments.
Metastatic symptoms:
- weight loss and loss of appetite
- bone pain, with or without pathologic fracture (because prostate cancer, when metastatic, has a strong predilection for bone)
- lower extremity pain and edema (due to obstruction of venous and lymphatic tributaries by nodal metastasis)
- Uremic symptoms can occur from ureteral obstruction caused by local prostate growth or retroperitoneal adenopathy secondary to nodal metastasis.
35
Q
What are the screening options for prostate cancer?
A
Screening options include:
- Digital rectal exam revealing a hard nodular prostate.
- Prostate specific antigen (PSA)
- Some investigators are now recommending investigation of levels over 2.5 ng/mL. In the past 4.0 ng/mL was considered the cutoff value.
- Recent research findings indicate that for patients having prostatectomy, the risk of death from prostate cancer is directly related to the rate of rise in the PSA during the year prior to diagnosis.
- Prostate specific antigen (PSA)
Benign disorders, e.g. BPH, prostatitis, prostatic infarction, vigorous massage or biopsy may cause a false rise in PSA
36
Q
Describe the pathophysiology associated with colon cancer
A
- Genetic and environmental factors are associated with the development of colorectal cancer
- It can develop through molecular pathways, gene mutations, and genomic instability.
- 25% of cases are inherited through gene mutations (mostly autosomal dominant)
- 75% of cases are acquired through environmental factors or random mutations
- Most are adenocarcinomas that develop from colonic epithelial tissue. Most begin as adenomatous polyps that form in an area of epithelial cell hyperproliferation and crypt dysplasia. Once the adenoma traverses the muscle it becomes highly invasive and highly malignant.
- Most cases progression from adenoma to carcinoma occurs over a 5-10 year period.
- The majority originate in the left side of the colon and grow to form an ulcer that encircles the bowel making the lumen smaller than normal
- Right sided tumors grow into the bowel lumen. The incidence of these is increasing.
37
Q
What are the risk factors associated with colon cancer?
A
- Age: incidence increases after age 40 with an even greater increase after age 50. Approximately 90% of cases occur in persons older than 50.
- diet: A high fat diet, especially animal fat, is thought to increase exposure to more bile salts for a longer period of time
- Genetics: There is an increased incidence among first degree relatives. Also familial adenomous polyposis is associated with a high risk for cancer development
- other risk factors: inflammatory bowel disease, polyps, abdominal or pelvic radiation, prior history of colon cancer, physical inactivity, obesity, smoking, more than 2 alcoholic beverages per day
38
Q
What are the signs and symptoms associated with colon cancer?
A
- right side tumor: melena, anemia, abdominal mass, pain, indigestion, weight loss, fatigue
- transverse colon tumor: bloody stools, changes in bowel habits, obstructive symptoms, palpable mass
- left side tumor: constipation, signs of obstruction, change in bowel habits, blood-streaked stools, cramping and gas, decrease in stool diameter, feeling of incomplete evacuation
- rectal tumor: tenesmus, urgency, blood in stools
