Tumor Pathology 5

Question 1

Describe how certain genes – HER2, BRAF, retinoblastoma gene, mismatch repair proteins, p53 – have a role in certain cancers.

Answer 1

HER2: Overexpression causes aggressive growth in breast, gastric, and other cancers.

BRAF: Mutations (e.g., V600E) drive cancer progression, particularly in melanoma, colon, and thyroid cancers.

RB1: Loss of function leads to unregulated cell cycle progression and is associated with retinoblastoma and other cancers.

Mismatch Repair Proteins: Defects cause microsatellite instability and are linked to Lynch syndrome and various cancers.

p53: Mutations result in loss of cell cycle control and apoptosis, driving the development of many cancers.

Question 2

Describe how certain environmental factors may cause cancer with reference to smoking, Human Papilloma Virus and alcohol.

Answer 2

1. Smoking
   > Mechanism:
   - Chemical Carcinogens: Tobacco smoke contains over 7,000 chemicals, many of which are known carcinogens. Key carcinogens include benzene, formaldehyde, and polycyclic aromatic hydrocarbons.
   - DNA Damage: These chemicals can cause direct DNA damage, leading to mutations in genes that regulate cell growth and division, including oncogenes and tumor suppressor genes.
   - Inflammation: Smoking induces chronic inflammation in the lungs and other tissues, creating an environment conducive to cancer development.

> Associated Cancers:
- Lung Cancer: Smoking is the leading cause of lung cancer, responsible for approximately 85% of cases.
- Other Cancers: It is also linked to cancers of the mouth, throat, esophagus, bladder, kidney, pancreas, and cervix.

2. Human Papillomavirus (HPV)
   > Mechanism:
   - Viral Integration: HPV, particularly high-risk strains like HPV 16 and 18, can integrate its DNA into the host cell’s genome. This can disrupt normal cellular processes.
   - Oncoproteins: HPV produces oncoproteins (E6 and E7) that inactivate key tumor suppressor proteins, such as p53 and Rb. This leads to unchecked cell proliferation and disruption of the cell cycle.
   - Inflammatory Response: Persistent HPV infection can trigger chronic inflammation, further promoting changes in the epithelium that can lead to cancer.

> Associated Cancers:
- Cervical Cancer: HPV is the primary cause of cervical cancer, with nearly all cases linked to the virus.
- Other Cancers: HPV is also associated with cancers of the oropharynx, anus, vulva, vagina, and penis.

3. Alcohol
   > Mechanism:
   - Acetaldehyde Production: Alcohol metabolism produces acetaldehyde, a toxic compound and probable human carcinogen. Acetaldehyde can damage DNA and disrupt cellular function.
   - Oxidative Stress: Alcohol consumption leads to the production of reactive oxygen species (ROS), which can cause oxidative stress, resulting in further DNA damage.
   - Hormonal Changes: Alcohol may influence hormone levels, such as increasing estrogen levels, which can contribute to hormone-related cancers, particularly breast cancer.

> Associated Cancers:
- Breast Cancer: Alcohol consumption is a known risk factor for breast cancer, with risk increasing with higher intake.
- Liver Cancer: Chronic alcohol abuse can lead to liver cirrhosis, which significantly increases the risk of liver cancer.
- Other Cancers: Alcohol is also linked to cancers of the mouth, throat, esophagus, and colorectal region.

Summary
Environmental factors such as smoking, HPV, and alcohol significantly contribute to cancer risk through various mechanisms, including DNA damage, chronic inflammation, and metabolic byproducts. Understanding these connections is crucial for cancer prevention strategies, such as promoting smoking cessation, HPV vaccination, and responsible alcohol consumption.