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Questions and Answers
What is the main characteristic of cancer?
What is the leading cause of death in developed countries?
What percentage of tumors have a mutation in the p53 gene?
What is the role of the RB1 gene?
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What is the result of mutated BRCA1 or BRCA2 genes?
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What is the goal of personalized medicine in cancer therapy?
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What is the name of the protein produced by the BCR-ABL hybrid gene?
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What is the role of the Ras protein?
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What percentage of colon cancer is associated with Hereditary Nonpolyposis Colon Cancer (HNPCC)?
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What is the result of a mismatch repair deficiency?
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What is the name of the gene that is often mutated in Chronic Myelogenous Leukaemia (CML)?
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What is the name of the condition where multiple polyps grow in the large intestine?
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What is the name of the drug that targets the BCR-ABL hybrid gene?
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What is the role of the APC gene?
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What is the result of a mutation in the K-RAS gene?
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What is the percentage of cancers associated with viruses?
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What is the role of the p53 gene?
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What is the main effect of the viral E7 protein in cervical cancer?
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What is the estimated percentage of skin cancers caused by sunlight or tanning beds?
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What is the name of the genes that are mutated in Hereditary Nonpolyposis Colon Cancer (HNPCC)?
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Study Notes
What is Cancer?
- Cancer is a phenotype produced by the environment and a person's genotype.
- It is a group of diseases affecting many different cells and tissues in the body.
- Two main characteristics of cancer:
- Uncontrolled cell division.
- Ability of cells to spread (metastasis).
Causes of Cancer
- Several different causes:
- Genetic predisposition.
- Mutagenic chemicals.
- Some viruses.
- Chromosomal changes.
- Environmental factors.
- Time.
- Mutation is the starting point for all cancers.
Sporadic vs Familial Cancers
- Most cancers are sporadic (accumulation of mutations over time).
- Environmental factors can speed up the process.
- At least two mutations are required.
- Some cancers are familial (e.g., inherited breast cancer).
- These have helped identify cancer genes.
- Inherit one mutated gene, then the normal gene mutates too (Loss of Heterozygosity, LOH).
Inheritable Susceptibilities
- Examples of inherited cancer genes:
- BRCA1 and BRCA2 (breast cancer).
- FAP1 (familial adenomatous polyposis).
- MSH2 (Lynch Syndrome I).
- LFS1 (Li-Fraumeni Syndrome).
- MEN1 (multiple endocrine neoplasia type I).
Progression of Cancer
- All cancers start in a single cell.
- Mutations accumulate over time until the cell becomes cancerous.
- Once formed, cancer cells divide continuously.
- Further mutations accumulate, making the cancer more aggressive.
- Cancer cells become invasive and can colonize new areas.
Types of Cancer
- Classified by:
- Tissue or organ of origin (e.g., carcinoma, sarcoma, leukaemia).
- Location (e.g., skin, lung, colon).
Cell Cycle Checkpoints
- G1/S Checkpoint: checks internal and external conditions.
- G2/M Checkpoint: checks that all DNA has been copied and any mistakes have been repaired.
- M Checkpoint: checks that chromosomes are lined up correctly.
Tumour-Suppressor Genes and Oncogenes
- Tumour-suppressor genes: decrease or stop cell division (e.g., RB1).
- Oncogenes: drive cell division in response to signals received (e.g., Ras).
DNA Repair and Genome Stability
- All cancers result in some form of genomic instability.
- Aneuploidy, loss of chromosomes, duplications, deletions, inversions, etc.
- Result from a loss of the ability to repair DNA damage.
Genes and Cancer
- Examples of genes involved in cancer:
- Retinoblastoma (RB1).
- Ras.
- BRCA1 and BRCA2.
- p53.
BRCA-Related Genome Instability
- BRCA1 and BRCA2 mutations account for 15-20% of hereditary breast cancers.
- Associated with increased risk of breast, ovarian, and prostate cancer.
The Pathway to Colon Cancer
- >6 mutations required to form cancer.
- Genetic and environmental factors.
- Mostly sporadic, ~5% inherited.
Familial Adenomatous Polyposis (FAP)
- Accounts for ~1% of all colon cancers.
- 100% lifetime risk of developing colon cancer.
- Associated with chromosomal instability.
- Requires 5-7 mutations.
- Order of mutations is important.
Hereditary Nonpolyposis Colon Cancer (HNPCC)
- Mutations in 7 different genes lead to HNPCC.
- Mutations in MSH2 and MLH1 cause 90%.
- Associated with increased risk of colon, stomach, pancreas, endometrial, and ovarian cancer.
Chromosomal Rearrangement and Cancer
- Several cancers are associated with translocations (e.g., Chronic Myelogenous Leukaemia (CML)).
Cancer is a Genomic Disease
- Accumulation of mutations throughout the genome.
- DNA sequencing, family studies, and GWAS are helping identify cancer-causing changes.
Better Identification of Cancer Genes
- Genes in normal tissue can be compared to genes in cancerous tissue.
- Identifies which mutations have occurred.
Epigenetics and Cancer
- DNA and histone modifications can lead to cancer.
- Allows cells to proceed through the cell cycle with damaged DNA.
Targeted Cancer Therapy
- Affects only cancer cells.
- Selectively blocks oncogenes and slows cell division.
- Two types of drugs – small molecules and monoclonal antibodies.
Environmental Effects on Cancer
- Viruses, chemicals, radiation, diet, smoking, sun exposure, etc. can all damage DNA.
Viruses and Cancer
- 15% of cancer associated with viruses.
- Examples: HPV16 and HPV18 causing cervical cancer.
Other Environmental Agents
- Smoking: 75-85% of smokers develop cancer.
- Sun exposure: 95-99% of skin cancers.
Reducing Your Risks
- Various ways to reduce the risk of cancer.
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Description
This quiz covers the basics of cancer, its characteristics, and the relationship between genotype and phenotype. It also discusses the impact of medical treatments on life expectancy and cancer risk.
