Week 2 Study Guide - Genetics and Cancer

What does autosomal dominance and autosomal recessive mean?

 Autosomal Dominance: an affected individual has 1 copy of a mutant

gene and 1 normal gene

 Autosomal Recessive: passed down through families, 2 copies of an

abnormal gene

What are sex-linked genetic characteristics?

 Klinefelters syndrome: extra x chromosome (XXY)

 Tuners Syndrome: missing all or part of x chromosome (XO)

 Down syndrome: extra chromosome 21

Describe the etiology (genetics, incidence), clinical manifestations

and risk factors of Marfan syndrome, Kleinfelter’s syndrome, Turner’s
syndrome and Down’s syndrome.
Genetics Incidence Clinical Manifestations Risk Factors
Marfan Dominance- 1 in 20,000, Connective tissue disorder Genetic
Syndrome men and – long, thin body. Condition-
affects gene controlling women Arachnodactyly, chest & risk is high if
fibrillin-1 production spinal deformities, cardiac parent has
issues this
Kleinfelters Polysomy: Extra X 1 in 500- Tall, gynecomastia, wide Maternal risk
Syndrome chromosome 600 males hips, decreased pubic hair after age 35,
(feminine), lack of facial
hair
Turners Monosomy: Missing all 1 in 2000 Small stature, broad High BP,
Syndrome or part of X females chest, ovarian dysgenesis,
multiple pigmented nevi,
hearing loss
Down Trisomy: Extra 21 1 in 700 Epicanthal folds, slanted Maternal risk
syndrome eyes, flat facial profile, high at 30,
malformed eyes, CHD, 1:25 at 45
protruding tongue, short years of age
broad hands
Describe the etiology and manifestations of neurofibromatosis

 Etiology: Neurogenic Tumors- from nerve cells

o NF 1 recklinghousen disease most common

o Soft pandiculation lesions

o Pheochromocytomas- adrenals

 Symptoms:

o Pigmented iris nodules

o Pigmented café au lait spots (birth marks)

o Neurological issues- ADD, learning disabilities

o Optic gliomas – dots on iris

 Manifestations: headache, hearing loss, lisch nodules, soft lesions

Discuss the genetics and manifestations of Tay Sachs disease

 Genetics: Autosomal Recessive – can go genetic testing

 Manifestations:

o Lipid accumulation in lysosomes

o Brain and retinal neurons are destroyed

o Progressive weakness and muscle flaccidity (6-10 months)

o seizures, blindness, deafness, decreased muscle tone,

increased startle.

What is a multifactorial genetic disorder?

  A condition caused by many contributing factors

o Genes and Environment

o Congenital disorders

 Cleft lip/ palate, clubfoot, congenital heart disease

o Disorders later in life

 CHD, Cancer, DM, HTN, Mental illness

o Involve single organ or tissue

When is a fetus most susceptible to congenital defects?

 1st trimester day 15- 60 after conception

o Mothers health

 Diabetes- high birth weight

 Smoking- low birth weight

 Rubella- low birth weight

 Alcohol- fetal alcohol syndrome

 Facial features

o Teratogenic agents

 Radiation- x rays

 Chemicals and drugs

 Vitamin A overdose- Accutane (cleft palate)

 Thalidomide – phocomelia (no hands)

o TORCH: Common Manifestations

  Microcephaly

 Hydrocephalus

 Eye defects

 Hearing deficits

o Nutrition

 Anencephaly- missing forebrain, cerebrum

 Spina Bifida- incomplete tube closure

What causes cleft palate/cleft lip?

 Cause: Vitamin A overdose – Accutane

 Craniofacial and maxillary fusion process (day 35)

 Feeding and speech

 Genes

 Drugs

 Viruses

 toxins

What is TORCH syndrome? What are the common manifestations?

 T- toxoplasmosis

o Undercooked meats, cat litter

 O- other

o EBV, herpes zoster, syphilis, HIV

 R- rubella
 o Hearing impairment, blindness, neurological issues

 C- cytomegalovirus

o Organomegaly, microcephaly, brain, ureter, renal dilation

 H- herpes simplex 2

How and when does fetal alcohol syndrome occur?

 How: Alcohol passes freely through placental barrier

 When: before or right after birth

 Manifestations:

o Short palpebral fissure length

o Smooth philtrum (above top lip, under nose)

o Thin upper lip

Describe the prenatal testing that can be done for fetal genetic
defects.

 Chronic Villus Sampling (CVS)

What are the differences between benign and cancerous cells?

 Benign Tumor (non-cancerous)

o Well organized

o Encapsulated

o Normal cell structure

o Well differentiated
 o Non- invasive

o Slow growing, expansion

o Localized

 Malignant Tumor (Cancerous)

o Grow rapidly: high mitotic rate

o Loss of differentiation: anaplasia

o Genetic instability/ aneuploidy

o Cells varying shapes and sizes (pleomorphic)

o Not encapsulated

o Grows by invasion

o Metastasize

How do you classify tumors? (Grading, Staging, TNM)

 Grading: microscopic examination of differentiation

o I = well differentiated

o IV = poorly differentiated

 Staging: clinical, radiographic, surgical examination of extent and

spread

o Stage I: Confined to organ of origin

o Stage II: locally invasive

o Stage III: Spread to regional lymph

o Stave IV: Distant Spread

  TNM System:

o T (1-4) = tumor size

o N (0-3) = Node Involvement

o M (0-1) = Metastasis

How do you diagnose cancer?

 Tumor Markers (prostate- specific antigen)

o Substances produced by cancer cells

o Found on tumor plasma membranes, in blood, spinal fluid, or

urine

 Cytologic studies (pap smear)

 Tissue Biopsy (fine needle aspiration)

 Immunohistochemistry (monoclonal antibodies)

o Monoclonal antibodies to ID cancer type, site of origin

 Microarray Technology (gene chips)

o Detect and quantify expression of large number of genes to ID

tumor types, prognosis and response to therapy

What is the role of oncogenes and tumor suppressor cells in causing

cancer cells to proliferate?

 Proto-oncogenes code for natural cell division proteins: mutate to

oncogenes

o Ocogenes: point mutation, translocation, multiple copies of

genes

 Increased or activated
  Increases cell division

 Tumor Suppressor cells: inhibit mutant cell proliferation

o Mutations inhibit or decrease activity

o Decrease cell division

How does angiogenesis occur?

 Chemical signs in the body

What is the purpose of angiogenesis?

 Formation of new blood vessels

 Growth of endothelial cells – line the inside wall of blood vessels

What role does angiogenesis play in metastasis?

  Essential component of the metastatic pathway

 These vessels provide the principle route by which tumor cells exit
the primary tumor site and enter the circulation

How do cancer cells metastasize?

 Cancer cells break off and leave tissue of origin and stare a new
cancer development in distant site
Where are the most common areas of metastasis?

 Lymphatic

o Lymph node
 o First node in drainage

o Sentinel node

o Lymphatic spread

 Blood vessels

o Loss of cellular adhesion

o Enzyme release to dissolve extracellular matrices (proteases)

o Gain access to blood vessel and arrive at a favorable site

o Invade tissue and establish blood supply

How do risk factors such as obesity, age, genetics, and immune

system function increase/affect risk of cancer?

How would you screen for cervical cancer, breast cancer and prostate
cancer? Are there differences in screening by age? What are they?
Screenings Age When

Cervical Pap Smear Women 21-65 Every 3 years

Women 30-65 Every 5 years

Breast Mammography Women 45 Every year

Women 55 Every other year

Prostate Colonoscopy Age 50 Every 10 years

Fecal Occult Blood Test Age 50 Yearly

PSA and DRE Men 50 Yearly

What are some of the side effects of cancer?

 Pain

 Bone marrow suppression (carrying oxygen, blood clotting)

 Infection

 Respiratory and circulatory effects

o SOB

o Plural effusion, pericardial effusion (water in lungs)

o Tumor pressing against vessel

 GI

o Obstruction

o Discomfort

 Increased confusion, agitation, hallucinations

 Depression

 Anxiety

What is paraneoplastic syndrome?

 A manifestation in sites unaffected by diseases

o Cancer cells can produce hormones

 Anti-diuretic hormone (Water retention)

 Adrenocorticotropic hormone (release cortisol, glucose)

 Parathyroid hormone (hypercalcemia)

o Cells can produce proteins that affect clotting

  Thrombosis

 Lambert eaton syndrome

What are the side effects of chemotherapy and radiation? What

tissues are most susceptible? Why?

Side Effects Tissue

Chemo Localized: ulcerated mucous Breast cancer, head and neck, lung,
membrane, infection, bleeding, GI, ovarian, testes
radiation burns, New Cancer.

Systemic: Fatigue, Anemia

Radiatio Nausea/ Vomiting, Mucositis, stomatitis, Prostate, thyroid,
n bone marrow suppression, Fatigue,
diarrhea, alopecia
Hormone Hot flashes, vaginal discharge, fatigue, breast, prostate, endometrium, ovaries
nausea, joint and muscle pain

Surgery Pain, swelling, wound, incision site, Diseased Tissue

bruising, numbness bleeding, fatigue

How does radiation work?

 Treatment of choice for some tumors to kill or reduce tumor, relieve

pain or obstruction

o Destroy rapidly diving cancer cells with minimal exposure to

normal cells

o Kill, delay, halt cell division

o Cells die or are unable to divide

How does chemotherapy work? 

 Chemotherapy is the use of drugs/chemical agents to destroy cancer

cells by stopping their ability to grow and divide.
  Cell-kill hypothesis: with each cell cycle is a percentage (20-99%) of
cancerous cells are killed

 Repeating chemo kills more cells until those left can be handles by
the bodys immune system

What is different about hormone therapy for cancer?

 Drugs that deprive cancer cells of needed hormone signals to divide