Cancer

What is the basic definition of cancer?

A group of diseases characterized by uncontrolled cell proliferation.

Which type of cancer originates from epithelial tissues?

Carcinoma.

What percentage of cancers are carcinomas?

Approximately 90%.

What is the difference between carcinoma and sarcoma?

Carcinomas originate from epithelial tissues, sarcomas from connective tissues.

What type of cancer originates from blood-forming tissues?

Hematopoietic malignancies (e.g., leukemia, lymphoma).

What is the meaning of neoplasia?

New, abnormal growth of tissue, which can be benign or malignant

Define hyperplasia.

Increased cell number without change in cell type.

What is metaplasia?

A reversible change where one cell type is replaced by another.

What does dysplasia indicate?

Abnormal cell morphology; often a pre-cancerous state.

What is anaplasia?

Loss of cellular differentiation; often seen in aggressive cancers.

How does benign differ from malignant tumors?

Benign tumors are localized and non-invasive; malignant tumors invade and metastasize.

What cancer is used as an example of observable histological progression?

Retinoblastoma.

What does the TNM staging system stand for?

Tumor size (T), Node involvement (N), Metastasis (M).

What is Tis in the TNM system?

Carcinoma in situ (pre-invasive stage).

What is the most common environmental cause of cancer?

Carcinogens, such as tobacco smoke.

Name a well-known study linking occupational exposure to cancer.

Percival Pott's study linking chimney sweeps to scrotal cancer.

How does UV radiation cause cancer?

By causing cyclobutane pyrimidine dimers (CPDs) in DNA.

What is the Ames Test used for?

To detect mutagenic potential of substances.

What type of agent is benzo(a)pyrene?

A carcinogen found in cigarette smoke, causing DNA mutations.

What key historical event established that coal tar can cause tumors?

Yamagiwa's rabbit ear experiments in 1915.

What does the 'bad luck' hypothesis of cancer suggest?

Many cancers result from random mutations during DNA replication.

Who proposed that DNA replication errors explain cancer variability among tissues?

Tomasetti & Vogelstein.

Does the 'bad luck' hypothesis imply prevention is useless?

No, prevention remains critical as environmental factors are still significant.

What is the EHR model of cancer causation?

Environment, Heredity, Replication.

What percentage of cancers are considered preventable according to the EHR model?

Varies by cancer type; lung, melanoma, cervical can be up to 85-100%.

Give an example of a preventable cancer type.

Lung cancer (smoking cessation).

What is the lifetime risk of lung cancer?

Approximately 6.9%.

Is small intestine cancer more or less common than brain cancer?

Less common despite higher exposure to mutagens.

How do lifestyle factors impact cancer risk?

Significantly; e.g., Seventh-day Adventists have half the cancer rate of the general population.

How does migration influence cancer risk?

Immigrants often adopt cancer risks of their new environment (e.g., Japanese in Hawaii).

What key factors in the EHR model can be modified?

Environmental exposures like smoking, UV exposure, infections.

Does DNA replication error alone explain all cancer risk?

No, it explains tissue variability but not the overall rate.

What percentage of cancers globally are linked to infectious agents?

About 20%.

Give an example of a virus that contributes to cancer.

HPV causing cervical cancer.

What proportion of cancer variability between tissues is explained by DNA replication errors?

Around 66%.

How does the microbiome relate to cancer risk?

Microbiome composition influences tumor behavior and risk.

How does living in the USA affect immigrants' microbiomes?

Shifts microbiomes, linked to obesity and potentially cancer risk.

What model integrates molecular data with epidemiology for cancer causation?

The EHR model (2018).

Why is the study of cancer origins clinically important?

It informs prevention, diagnosis, and treatment strategies.

Does the 'bad luck' hypothesis dismiss lifestyle interventions?

No, lifestyle changes remain essential for cancer prevention.

Who proposed the original 'Hallmarks of Cancer' model?

Hanahan and Weinberg in 2000.

Name two hallmarks added in the 2011 update.

Reprogramming energy metabolism and evading immune destruction.

What are the enabling characteristics of cancer?

Genome instability & mutation, tumour-promoting inflammation.

What is self-sufficiency in growth signals?

Cancer cells can grow without external signals.

What does 'insensitivity to growth-inhibitory signals' mean?

Cancer cells ignore signals that normally suppress growth.

How do cancer cells evade apoptosis?

By disabling programmed cell death pathways.

What is meant by limitless replicative potential?

Cancer cells maintain telomere length to avoid senescence.

What hallmark involves inducing blood vessel formation?

Sustained angiogenesis.

Define tissue invasion and metastasis.

Spread of cancer cells beyond their site of origin.

What is the Warburg effect?

Cancer cells prefer glycolysis over oxidative phosphorylation even in oxygen presence.

Which pathway is often activated to support sustained proliferation?

EGFR/RTK signaling pathway.

Which checkpoint is critical in the G1 phase of the cell cycle?

The Restriction (R) point.

What tumour suppressor controls the R-point?

RB1 (pRB).

What is the significance of pRB in cancer?

It is often inactivated, removing growth control.

What does tumour-promoting inflammation contribute to?

Supports proliferation, angiogenesis, and invasion.

What is the role of genome instability?

Provides mutations necessary for cancer evolution.

How do cancer cells evade immune destruction?

By downregulating MHC, secreting suppressive cytokines, and expressing checkpoint molecules.

What are receptor tyrosine kinases (RTKs)?

Cell surface receptors often mutated in cancer for continuous signaling.

Name a cancer type with common EGFR mutations.

Lung adenocarcinoma.

Why is the Hallmarks of Cancer model clinically useful?

It guides the development of targeted therapies.

What is the initial error rate of DNA polymerase delta?

1 error per 10⁵ bp.

How does proofreading improve DNA replication fidelity?

Reduces error rate to 1 in 10⁷ bp.

What repair mechanism fixes mismatches post-replication?

Mismatch Repair (MMR).

Deficiency in MMR leads to which syndrome?

Lynch Syndrome (HNPCC).

What cancers are common in Lynch Syndrome?

Colon, endometrial, ovarian, stomach.

What is MSI (Microsatellite Instability)?

A hallmark of defective MMR; used in diagnostics.

Which gene is commonly methylated in sporadic MSI+ cancers?

MLH1.

What does the NER pathway repair?

Bulky DNA lesions, like UV-induced damage

What genetic disorder is linked to defective NER?

Xeroderma Pigmentosum (XP).

What does double-strand break (DSB) repair prevent?

Chromosomal breakage, translocations, and oncogenesis.

What are the two main DSB repair pathways?

Homologous recombination (HR) and Non-homologous end joining (NHEJ).

Which is error-prone: HR or NHEJ?

NHEJ.

Which complex senses DSBs?

MRN complex.

What is BRCA1's role in DSB repair?

Acts as a scaffold protein recruiting other repair proteins.

What is the role of RAD51?

Facilitates homologous strand invasion during HR.

BRCA mutations predispose individuals to which cancers?

Breast and ovarian cancer.

What is the TRAP assay used for?

Detects telomerase activity.

What is the function of DNA pol η (XPV)?

Allows error-free bypass of UV-induced lesions.

What is CIMP phenotype?

CpG island methylator phenotype; leads to gene silencing in cancer.

What therapy benefits MSI+ tumors due to their high neoantigen load?

Immune checkpoint blockade therapy.

What percentage of cancers worldwide are caused by viruses?

10-15%.

What is the latency period for virus-induced cancers?

5-50 years.

Which virus was discovered by Peyton Rous?

Rous Sarcoma Virus (RSV).

What gene does RSV carry that causes cancer?

v-src.

What is the human counterpart of v-src?

c-src, a proto-oncogene.

How does RSV integrate into host DNA?

As a retrovirus, via reverse transcription.

Name one RNA human tumour virus.

HTLV (Human T-cell Leukemia Virus).

Which DNA virus causes cervical cancer?

Human Papillomavirus (HPV).

What does HPV E6 protein do?

Degrades p53, preventing apoptosis.

What does HPV E7 protein do?

Inactivates pRB, releasing E2F.

Which virus causes hepatocellular carcinoma?

Hepatitis B Virus (HBV).

What is the key oncogenic protein in HBV?

HBX.

Which virus causes Burkitt lymphoma?

Epstein-Barr Virus (EBV).

What bacterium is linked to gastric cancer?

Helicobacter pylori.

How does H. pylori promote cancer?

Chronic inflammation and CagA protein disrupt polarity.

How do DNA tumour viruses induce cancer?

By inactivating tumour suppressor proteins.

Which viruses are associated with insertional mutagenesis?

RNA tumour viruses.

What is ADEPT therapy?

Antibody-Directed Enzyme Prodrug Therapy using antibodies linked to enzymes.

What is the mechanism of viral-induced cancer from RNA viruses?

Activation of oncogenes via integration.

What vaccine prevents HPV-related cancers?

HPV vaccine.