Skin Cancer Detection & Genetic Testing: ABCDEs, Viruses, and Molecular Markers

What tools are needed for a full skin self-exam?

Two mirrors (full-length + hand-held), bright lighting, comb for scalp.

What body areas must be checked during a skin self-exam?

Underarms, forearms, palms, legs, between toes, soles, scalp, neck, back, buttocks.

What does A in ABCDE stand for and what does it indicate?

Asymmetry — uneven growth suggests uncontrolled cell division.

What does B stand for?

Border irregularity — jagged or blurred edges suggest abnormal growth.

What does C stand for?

Color variation — multiple colors suggest melanoma.

What does D stand for?

Diameter > 6 mm (larger than pencil eraser).

What does E stand for and why is it most important?

Evolving — change in size, shape, color, itching, bleeding.

Which skin cancer is most common?

Basal cell carcinoma (~80%).

Which is most deadly?

Melanoma.

Where does basal cell carcinoma originate?

Basal layer of epidermis.

What are the characteristics of basal cell carcinoma?

Slow growing, pearly bump, rarely metastasizes.

What are the characteristics of squamous cell carcinoma?

Scaly red patch, can metastasize, arises from squamous cells.

Why is melanoma highly metastatic?

Melanocytes can invade bloodstream/lymph quickly.

What determines melanoma prognosis?

Tumor thickness (Breslow depth).

What virus is linked to Merkel cell carcinoma?

Merkel cell polyomavirus.

What type of cells does Kaposi sarcoma affect?

Endothelial cells lining blood vessels.

What virus causes Kaposi sarcoma?

Human herpesvirus 8 (HHV-8).

Who is at high risk for Kaposi sarcoma?

Immunocompromised individuals.

What is the primary environmental risk factor for skin cancer?

UV radiation.

Why does fair skin increase risk?

Less melanin → less UV protection.

Why does age increase risk?

Accumulated DNA damage over time.

Why does weakened immunity increase risk?

Reduced tumor surveillance.

What percentage of cancers are sporadic?

~70-80%.

Define sporadic cancer.

Random mutation; no inherited mutation.

Define familial cancer.

Clusters in families without clear single-gene inheritance.

Define hereditary cancer.

Caused by inherited mutation present at birth.

What percentage of cancers are hereditary?

~5-10%.

What type of gene are BRCA1/2?

Tumor suppressor genes.

What is the normal lifetime breast cancer risk?

~12%.

What is the BRCA mutation lifetime breast cancer risk?

~45-80% depending on gene.

Why does BRCA mutation increase risk?

Impaired DNA repair.

What is the 'two-hit hypothesis'?

Both copies of tumor suppressor must be mutated.

How do lifestyle factors affect BRCA carriers?

Increase DNA damage → higher chance second allele mutates.

What is an STR?

Short tandem repeat — 2-6 base pair sequence repeated.

Are STRs coding or non-coding?

Non-coding (introns).

Why are STRs useful?

Highly polymorphic; vary between individuals.

What defines an STR allele?

Number of repeats.

If one parent gives 10 repeats and the other 15, what is the genotype?

10,15.

What is PCR used for in marker analysis?

Amplifies STR region.

Why does DNA move in gel electrophoresis?

Negative charge → moves toward positive electrode.

What moves farther in gel: small or large fragments?

Small fragments.

What does each band represent?

One allele.

What does two bands at a locus mean?

Heterozygous.

What does one band mean?

Homozygous.

What is a DNA ladder?

Standard with known fragment sizes.

How can STRs indicate presence of BRCA mutation?

If STR is linked to mutated gene, inherited together.

Which virus causes cervical cancer?

Human papillomavirus (HPV).

What vaccine prevents HPV?

HPV vaccine (Gardasil).

Which virus causes mononucleosis?

Epstein-Barr virus (EBV).

What cancers are linked to EBV?

Burkitt lymphoma, Hodgkin lymphoma, nasopharyngeal carcinoma.

Which viruses cause liver cancer?

Hepatitis B and Hepatitis C.

Is there a vaccine for Hepatitis B?

Yes.

Is there a vaccine for Hepatitis C?

No.

Which virus causes adult T-cell leukemia?

HTLV-1.

Which virus is linked to Merkel cell carcinoma?

Merkel cell polyomavirus.

Which virus causes Kaposi sarcoma?

HHV-8.

When do Pap smears start?

Age 21.

What is the Pap smear frequency for ages 21-29?

Every 3 years.

What is the Pap + HPV testing frequency for ages 30-65?

Every 5 years.

When does colorectal screening start?

Age 45.

What is the colonoscopy frequency?

Every 10 years.

What is the starting age for mammograms?

40-45 depending on guideline.

What is the mammogram frequency for ages 45-54?

Annually.

At what age should PSA screening discussions begin?

Around 50 (earlier if high risk).

What is the most common age for testicular cancer?

15-35.

Why is melanoma more likely to metastasize than basal cell carcinoma?

Melanocytes are in the basal layer but produce melanin and have access to lymphatic and blood vessels. BCC rarely invades vessels; melanoma spreads quickly.

Why does UV exposure increase skin cancer risk?

UV damages DNA directly (pyrimidine dimers) and indirectly (reactive oxygen species), causing mutations in tumor suppressor genes.

How does aging contribute to cancer risk?

Accumulated DNA mutations over time, reduced repair efficiency, weaker immune surveillance.

Why do immunocompromised individuals get more viral cancers?

Reduced immune surveillance allows virus-infected cells to survive and become malignant.

How does a BRCA mutation cause cancer at the DNA level?

BRCA proteins repair double-strand DNA breaks. Mutation → defective repair → genomic instability → tumor formation.

Why does environmental damage (like smoking or UV) increase risk in BRCA carriers?

Increases likelihood the second healthy allele gets damaged ('second hit'), triggering tumor formation.

Compare sporadic, familial, and hereditary cancers.

Sporadic: random mutations, no inheritance; Familial: clusters in families, multiple genes, environmental influence; Hereditary: single inherited mutation, early onset, passed parent → child.

Compare basal cell carcinoma, squamous cell carcinoma, and melanoma.

BCC: most common, slow, rare metastasis, pearly bump; SCC: less common, slow, can metastasize, scaly patch; Melanoma: rare, highly metastatic, originates in melanocytes, deadly.

Compare Merkel cell carcinoma and Kaposi sarcoma.

Merkel cell: aggressive, polyomavirus-linked, sensory cells, immunotherapy used; Kaposi sarcoma: endothelial cells, HHV-8, mostly immunocompromised, chemotherapy used.

Compare Pap smear, HPV testing, and mammogram.

Pap: cytology, 21+, every 3 years; HPV: DNA detection, 30+, every 5 years; Mammogram: X-ray, 40-45+, annual 45-54.

Compare colonoscopy vs flexible sigmoidoscopy.

Colonoscopy: entire colon, sedation, remove polyps, 10-year interval; Sigmoidoscopy: lower colon, no sedation usually, 5-year interval.

How does HPV cause cancer?

Viral proteins E6/E7 inactivate p53 and Rb tumor suppressors → uncontrolled cell cycle → cervical/anal/throat cancer.

How does chronic hepatitis B/C lead to liver cancer?

Persistent infection → chronic inflammation → hepatocyte turnover → mutations → hepatocellular carcinoma.

How does Epstein-Barr virus contribute to cancer?

EBV infects B cells → expresses latent proteins → inhibits apoptosis → lymphoma.

How can STR analysis identify alleles linked to mutations?

STRs near a gene are inherited together. Gel electrophoresis shows repeat lengths → indicates which allele is present.

Why are STRs better for identification than coding genes?

Non-coding STRs vary greatly between individuals (polymorphic), so patterns are unique fingerprints.

Why is PCR necessary before gel electrophoresis?

Amplifies tiny DNA regions (STRs) to detectable levels for band analysis.

How does gel electrophoresis separate DNA?

DNA is negatively charged → moves toward positive; small fragments move faster → fragments visualized as bands.

Why is BRCA considered a tumor suppressor?

Normally prevents cancer by repairing DNA; mutation disables this function → higher risk.

Why do BRCA carriers with bad lifestyle/environmental factors have higher risk?

Second hits from DNA damage more likely → mutation in remaining healthy allele → cancer develops sooner/more frequently.

What is the mechanistic difference between sporadic vs hereditary cancer at the cellular level?

Sporadic: both alleles acquire mutations over life; Hereditary: one allele already mutated at birth → only one hit needed to cause tumor.

Why do Merkel cell polyomavirus infections often result in cancer only in certain people?

Usually asymptomatic; immunocompromised or elderly → immune system can't clear infected cells → tumor forms.

Why is Kaposi sarcoma more common in HIV/AIDS patients?

Immunosuppression allows HHV-8 infected endothelial cells to proliferate → vascular tumors.

How does thickness of melanoma affect prognosis?

Thicker tumors → deeper invasion → higher chance of metastasis → worse survival.