Module 5 pt2

Hereditary cancer

cancer gene mutation present in every cell

familial cancer

increased risk of cancer in families compared to general population

Shared genetic and environmental factors

mutations in genetic material caused by

Radiation

Exposure to carcinogens

Infections

Failure of cellular proof-reading mechanisms

tumor suppressor

Inhibit proliferation

Control cell growth

Down regulate cell cycle

Repair DNA

Act as checkpoint for DNA damage

Mutations result in loss of function

proto-oncogene

become oncogene when mutated/deregulated (result=cancer)

code normal proteins promote

Cell growth and survival

Cause cellular proliferation

Inhibit cell death

Gain of function

2 hit hypothesis

cancer arises when both chromosomes have mutation

hereditary susceptibility=only 1 hit needed

initiation

Healthy → mutation → premalignant cell

promotion

Proliferation of premalignant cells

transformation

Second alteration produces malignant cell from premalignant cell

progression

Malignant cells divide forming clinical cancer

initiation of precursor process

precursor cell undergoes mutation that creates founding cancer cell

cell is deregulated to goes through replication=cancer

progression of cancer

Normal cell → hyperplasia → mild dysplasia → carcinoma in situ (severe dysplasia) → cancer (invasive)

metastatic cascade

tumor composed of transformed malignant cells that undergo mutations

right mutation + right combination = metastatic subcline that will invade blood vessels and go to other site

common sites: liver and lung

hallmarks of cancer

Evading apoptosis

Self-sufficiency in growth signals

Insensitivity to anti-growth signals

Sustained angiogenesis

Limitless replicative potential

Tissue invasion & metastasis

non modifiable risk factors

age (older=more frequent except sometimes children)

sex (men=higher risk)

ethnicity

geography

genetic susceptibility

preexisting conditions

reproductive history

modifiable risk factors

Smoking

Obesity

Physical activity

Diet

Alcohol consumption

Injection drug use

Sexual history

UV radiation exposure

carcinogens

cause genetic damage to cells

chemical, radiation, viral, microbial

human papilloma virus (HPV)

cervical, anal, oropharyngeal

HBV and HCV

hepatocellular ca

Epstein Barr VIrus (EBV)

lymphoma

human herpes virus 8 (HHV8)

kaposis sarcoma (HIV infected individuals)

human T-cell leukemia/lymphoma virus (HTLV-1)

adult T cell lymphoma

helicobacter pylori

gastric cancer

helocobacter pylori

gastric cancer

schistosoma

bladder cancer

screening

process of identifying asymptomatic individuals w elevated risk of cancer

earlier identification of disease allows:

Earlier diagnosis

Earlier treatment

opportunity to decrease morbidity & mortality from disease

cervical cancer screening

pap test (cytologic specimen)

colon cancer

fecal immunohistochemical test (FIT)

colonoscopy

breast cancer

mammography (X-ray/imaging detect lesions)

cancer screening

precursor lesion may be opportunity for screening & prevention

detect precaution lesion using screening test b4 development of cancer (prevent m&m in pt)

HPV

increase risk of cervical cancer

pap test performed detects dysplasia

treated before 10yrs usual development

vaccine=preventative measures

breast cancer

precursor: carcinoma in situ (DCIS)

detected by mammography

intervention=surgery (prevent growth)

colon cancer

precursor: colonic adenoma

adenoma bleeds & detected by FIT test/colonoscopy

principles of good screening test for cancer

test should b acceptable to those eligable (not too invasive/easy procedure)

should have high sensitivity (majority w cancer test positive)

shoudl shown reduced mortality in randomized controlled trials

gold standard of cancer diagnosis

tissue sampling

examination under microscope by pathologist

types of tissue sampling

biopsy

cytology (fine needle aspiration, body fluid)