CANCER'

What % of cancers are hereditary?

• Only about 5-10% of cancers are directly caused by inherited genetic mutations.

• Most cancers are sporadic, resulting from environmental exposures or lifestyle factors.

Initiation –

DNA damage or mutation occurs in a cell.

Promotion –

Mutated cell begins to divide uncontrollably, often influenced by environmental factors.

Progression –

Cancer cells grow aggressively, invade nearby tissues, and may metastasize.

Which enzyme blocks the shrinking of telomeres?

• Telomerase prevents telomere shortening.

• It adds repetitive sequences to the ends of chromosomes, allowing cancer cells to divide indefinitely.

Carcinomas vs. Sarcomas

Feature	Carcinomas	Sarcomas
Origin	Epithelial cells	Connective tissues (bone, fat)
Common Examples	Breast, lung, colon, prostate	Osteosarcoma, liposarcoma
Frequency	Most common (~85% of cancers)	Rare

Stage 0 –

Carcinoma in situ; abnormal cells present, but not spread.

Stage I –

Localized tumor, small and contained.

Stage II-III –

Regional spread to lymph nodes or nearby tissue.

Stage IV –

Distant metastasis.

Results of the 45 and Up Study

• A large Australian cohort study.

• Found that lifestyle factors (like physical activity and BMI) significantly influenced cancer risk.

• Showed that smoking, obesity, and inactivity were strong predictors of chronic disease and cancer.

Inflammatory Factor Contributing to Colon Cancer Risk

• Interleukin-6 (IL-6) is a major contributor.

• Chronic inflammation in the colon can promote tumor growth and cell proliferation.

Carcinoma in Situ vs. Invasive Carcinoma (Breast Cancer)

Feature	Carcinoma in Situ	Invasive Carcinoma
Spread	Confined to ducts/lobules	Has breached the basement membrane
Risk Level	Early, more treatable	More dangerous, can metastasize

How Much Does Increased Estradiol Raise Breast Cancer Risk

Elevated estradiol levels can increase breast cancer risk by up to 2-3 times, especially in postmenopausal women.

Why Increased Breast Cancer Risk After Menopause?

• Estrogen dominance without progesterone leads to unchecked cell proliferation.

• Estrogen is stored in body fat, which increases after menopause.

Increased Risk in Women Who’ve Never Given Birth

• Nulliparous women (never given birth) have 1.2 to 1.5 times greater risk.

• Pregnancy reduces lifetime estrogen exposure and promotes breast cell differentiation.

Results of the U of P Study

• Likely refers to a University of Pennsylvania study.

• Found that stress-related pathways and inflammation play a critical role in cancer progression.

• Showed how stress hormones can reduce immune surveillance.

By How Much Does Smoking Increase Lung Cancer Risk?

• Smoking increases lung cancer risk by 15 to 30 times.

• Accounts for over 85% of lung cancer cases.

Rates of Two Lung Cancer Categories

Category	Frequency
Non-small-cell	~85% of lung cancer cases
Small-cell	~15%, more aggressive Non-small-cell lung cancer accounts for about 85% of cases, while small-cell lung cancer accounts for approximately 15% and is known for being more aggressive.

Stages of Non-Small-Cell Lung Cancer (NSCLC)

• Stage I – Tumor in lung only.

• Stage II – Lung + nearby lymph nodes.

• Stage III – Lymph nodes in chest.

• Stage IV – Distant metastasis (e.g., brain, liver).

Results of the Henry Ford Health System Study

• Showed strong associations between physical activity, social support, and reduced cancer recurrence.

• Also linked stress management and immune function in cancer patients.

Two Types of Immunity

Innate

Immediate, non-specific defense (e.g., skin, phagocytes)

Adaptive

Specific, slower response (e.g., B and T cells)

Main Immunoglobulin for Immunity

IgG (Immunoglobulin G) provides 80% of total antibodies and long-term protection

How Antibodies Neutralize Viruses

• Bind to viral particles, blocking their entry into host cells.

• Mark them for destruction by macrophages and other immune cells.

B Cells:

Produce antibodies.

Helper T Cells (CD4+):

Activate B cells and other T cells.

Cytotoxic T Cells (CD8+):

Kill virus-infected or cancerous cells.

Key Activator of Helper T Cells:

Interleukin-1 (IL-1), presented by antigen-presenting cells.

Function of Perforin

• Released by cytotoxic T cells.

• Forms pores in target cell membranes, leading to cell death.

Function of Granulysin

• Antimicrobial and cytotoxic molecule.

• Induces apoptosis in tumor and infected cells.

IL-1:

Activates T cells, induces fever.

IL-2:

Promotes T cell proliferation.

IL-6:

Pro-inflammatory, promotes B cell differentiation.

IL-10:

Anti-inflammatory, regulates immune response.

Tumor’s Preferred Fuel Source

Glucose – used via aerobic glycolysis (Warburg effect), even in the presence of oxygen.

What Increases Natural Killer (NK) Cells Leaving the Spleen?

Epinephrine and Norepinephrine (stress hormones) mobilize NK cells.

Function of Corticotropin Releasing Hormone (CRH)

• Released from hypothalamus.

• Stimulates ACTH release, leading to cortisol production

Effect of Long-term Cortisol on Lymphocytes

Suppresses immune function, reduces lymphocyte proliferation, weakens defense.

Results of the 2019 Khosravi Meta-Analysis

• Found that regular exercise reduces markers of inflammation (e.g., CRP, IL-6).

• Promotes improved immune function, particularly in cancer survivors

Results of the 2016 Meta-analysis (Exercise + Breast Cancer Survivors)

• Acute exercise caused temporary immune activation, not suppression.

• Improved immune regulation and potentially lowered recurrence risk.

Does Intense Exercise Cause Immune Suppression?

• Only extreme or prolonged intense exercise (e.g., ultramarathons) can cause temporary suppression.

• Moderate-to-vigorous regular exercise is beneficial to immunity.

1987 LA Marathon Infection Rate Study

• Runners who competed: 13% reported upper respiratory infections.

• Runners who did not compete: 2% reported infections.

• Conclusion: Strenuous, prolonged exercise may temporarily suppress immunity.