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Questions and Answers
Which of the following conditions is primarily associated with inherited susceptibility to tumors?
Which of the following conditions is primarily associated with inherited susceptibility to tumors?
Which of the following oncogenes is associated with breast cancer?
Which of the following oncogenes is associated with breast cancer?
What stage of carcinogenesis involves the promotion of tumor growth after initiation?
What stage of carcinogenesis involves the promotion of tumor growth after initiation?
Which of the following factors is classified as an extrinsic factor contributing to tumor development?
Which of the following factors is classified as an extrinsic factor contributing to tumor development?
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Which of the following medical conditions is associated with an increased risk of malignancy?
Which of the following medical conditions is associated with an increased risk of malignancy?
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Which of the following represents an intrinsic factor associated with cancer development?
Which of the following represents an intrinsic factor associated with cancer development?
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What type of tumor is familial adenomatous polyposis predominantly associated with?
What type of tumor is familial adenomatous polyposis predominantly associated with?
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Which agent is known to induce mutations leading to cancer development?
Which agent is known to induce mutations leading to cancer development?
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What is the most important polycyclic aromatic hydrocarbon that is converted to its active form by hydroxylation?
What is the most important polycyclic aromatic hydrocarbon that is converted to its active form by hydroxylation?
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Which chemical compound is converted in the liver to a compound that contributes to bladder cancer?
Which chemical compound is converted in the liver to a compound that contributes to bladder cancer?
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Which virus is associated with Burkitt's lymphoma?
Which virus is associated with Burkitt's lymphoma?
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What type of cancer is associated with the hormonal factors mentioned in the content?
What type of cancer is associated with the hormonal factors mentioned in the content?
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Which of the following is a known environmental carcinogen linked to mesothelioma?
Which of the following is a known environmental carcinogen linked to mesothelioma?
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What is the role of oncogenes in cancer development?
What is the role of oncogenes in cancer development?
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Which genetic change can lead to the activation of oncogenes?
Which genetic change can lead to the activation of oncogenes?
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Which condition is characterized by a defect in DNA repair mechanisms leading to photosensitivity?
Which condition is characterized by a defect in DNA repair mechanisms leading to photosensitivity?
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What factor is NOT typically associated with an increased incidence of cancer?
What factor is NOT typically associated with an increased incidence of cancer?
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What type of genetic alteration is associated with Li Fraumeni syndrome?
What type of genetic alteration is associated with Li Fraumeni syndrome?
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Which type of damage to DNA is commonly caused by high doses of radiation?
Which type of damage to DNA is commonly caused by high doses of radiation?
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What role do promoters play in chemical carcinogenesis?
What role do promoters play in chemical carcinogenesis?
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What is a defining characteristic of direct-acting chemical carcinogens?
What is a defining characteristic of direct-acting chemical carcinogens?
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Which type of cancer has been linked to unprotected miners exposed to ionizing radiation?
Which type of cancer has been linked to unprotected miners exposed to ionizing radiation?
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Which of the following is NOT an extrinsic factor that can lead to DNA damage?
Which of the following is NOT an extrinsic factor that can lead to DNA damage?
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What is the consequence of the initiation step in chemical carcinogenesis?
What is the consequence of the initiation step in chemical carcinogenesis?
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What role does p53 play in cellular function?
What role does p53 play in cellular function?
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Which of the following statements about oncogenes is true?
Which of the following statements about oncogenes is true?
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How do mutations in DNA repair genes influence cancer development?
How do mutations in DNA repair genes influence cancer development?
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What percentage of retinoblastoma cases are familial?
What percentage of retinoblastoma cases are familial?
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What chromosomal location is associated with the p53 gene?
What chromosomal location is associated with the p53 gene?
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The progression phase in carcinogenesis is primarily characterized by what factor?
The progression phase in carcinogenesis is primarily characterized by what factor?
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What is a common outcome of familial retinoblastoma patients as they reach their teenage years?
What is a common outcome of familial retinoblastoma patients as they reach their teenage years?
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Which DNA repair system defect is specifically linked to cancer development?
Which DNA repair system defect is specifically linked to cancer development?
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Study Notes
Neoplasia III: Tumour Occurrence
- Tumour development is attributed to alterations or mutations in the genetic code.
- Tumours can be induced in somatic cells by extrinsic factors (carcinogens, chemicals, radiation, viruses) and intrinsic factors (heredity, 5%).
- Intrinsic factors include inheritance, host factors (age, immune system, hormones), and conditions predisposing to tumours (related to DNA repair).
- Inherited conditions increase susceptibility to specific or groups of tumours due to altered genes.
- DNA repair mechanisms play a vital role in preventing tumour development
- Defects in DNA repair mechanisms are associated with inherited predispositions to tumours. (Xeroderma pigmentosa, Ataxia telangiectasia, Fanconi's anaemia).
Objectives of Neoplasia
- Understand inherited susceptibility to tumour development (Xeroderma pigmentosa, Ataxia telangiectasia).
- Understand the inheritance of certain tumours (Familial adenomatous polyposis, Breast cancer, Retinoblastoma).
- Understand the functions of oncogenes and tumour suppressor genes (TSG) and their changes in neoplasia, particularly the role of oncogenes (ras, c-myc, c-erbB-2 (HER-2)) and TSG (retinoblastoma, p53).
- Recognize the stages in carcinogenesis (initiation, promotion).
- Identify agents that cause tumour development and their mechanisms of action (radiation, chemicals, viruses, hormonal, asbestos, aflatoxins, parasites).
- Identify occupations (asbestos exposure, dye industry) and medical conditions (ulcerative colitis, cirrhosis, Hashimoto's thyroiditis, chronic atrophic gastritis) associated with an increased risk of malignancy.
- Recognize geographical variations in the incidence of malignant tumours (gastric cancer, breast cancer, Burkitt's lymphoma).
Causes of Cancer
- Changes in genetic code (alterations/mutations) cause cancer.
- Extrinsic factors: Carcinogens, chemicals, radiation, some viruses.
- Intrinsic factors: Hereditary (5%).
Intrinsic Factors
- Inheritance: Inherited conditions predisposing to tumour development related to DNA repair.
- Host factors: Age, immune system, hormones.
Extrinsic Factors
- Radiation: (UV, ionizing)
- Chemicals: Polycyclic hydrocarbons, aromatic amines, nitrosamines
- Viruses: (Epstein Barr, Hepatitis)
- Other Factors: Hormones, Aflatoxins, Parasites
Radiation
- Evidence linking radiation to cancer includes skin cancer in radiologists, increased lung cancer risk in unprotected miners exposed to ionizing radiation, and increased risk of thyroid carcinoma in children from H&N radiotherapy.
- Hiroshima bombing: initial cancers included leukaemia and lymphoma; later-occurring cancers included breast and thyroid cancer.
- Radiation causes various DNA damage (single/double-strand breaks, base damage), the impact varies with exposure type and dose.
Chemical Carcinogenesis
- Carcinogens interact with DNA in various ways, causing specific base damage and single-strand breaks.
- Damage is often repaired, but potentially imperfectly.
- Carcinogens can be directly acting (with no metabolic conversion, like alkylating agents) or indirectly acting (requiring metabolic conversion, like polycyclic hydrocarbons).
- Polycyclic aromatic hydrocarbons (PAH) are found in coal tar and cigarette smoke; 3,4-Benzpyrene is an example.
- Aromatic amines (e.g., B-naphthalamines) are implicated in bladder cancer in certain industries.
- Nitrosamines form from dietary nitrates/nitrites in the gut, leading to gastrointestinal cancer.
Steps in Chemical Carcinogenesis
- Initiation: Exposure to sufficient dose of initiating agent causes permanent DNA damage (mutation) in a cell, making it capable of tumour development.
- Promotion: Promoters induce tumours in initiated cells, but they themselves are not tumorigenic. The tumour would not result if the promoter agent is applied before the initiating agent.
- Progression: Changes in multiple genes promote neoplastic cell growth.
Viruses
- Hepatitis B: Associated with hepatocellular carcinoma.
- Epstein Barr: Linked to Burkitt's lymphoma and nasopharyngeal carcinoma.
- Human Papillomavirus (HPV): Implicated in cervical carcinoma.
Other Agents
- Asbestos: Mesothelioma.
- Aflatoxins: Liver cancer.
- Schistosoma: Bladder cancer.
- Helicobacter: Gastric cancer and lymphoma
- Hormones (oestrogen and androgen): Breast and liver cancer respectively
Geographical Variation in Malignant Tumours
- Genetic factors: Tight family clusters linked to certain types of cancers.
- Viruses: Hepatitis B and Epstein-Barr viruses.
- Parasites: Schistosoma.
- Diet: Gastric cancer in Japan.
- Other factors: Reproduction and breast/cervical cancer.
Predisposing Factors
- Ulcerative colitis: Colorectal carcinoma
- Liver cirrhosis: Liver cancer
- Adenoma of the large intestine: Adenocarcinoma
Host Factors
- Age: Cancer incidence increases with age.
- Cumulative exposure to carcinogens.
- Latency.
- Accumulating genetic lesions
- Innate defence
- Immune factors
- Hormones
Molecular Bases of Cancer
- Cancer is a genetic disease, meaning tumour cells contain genetically altered DNA (point mutation, deletion, translocation).
- Cancer cells evade natural defence mechanisms like DNA damage repair and apoptosis.
Genes Involved in Cancer
- Oncogenes: Proto-oncogenes, altered (amplification, mutation, translocation) to oncogenes, contribute to uncontrolled cell growth and decreased apoptosis, e.g., c-myc, ras, c-erbB-2.
- Tumour suppressor genes: Normally suppress cell growth; loss/alteration leads to loss of growth suppression, e.g., Retinoblastoma protein (RB) and p53.
- DNA repair genes: Ensure accurate DNA copying during cell division; mutation increases other gene mutations, e.g., BRCA1, BRCA2, non-polyposis colon cancer (HNPCC) genes.
p53
- p53 is a tumour suppressor gene.
- It's a guardian of the genome.
- It's a transcription factor on chromosome 17q.
- Mutated in >50% of cancers
- It helps in cell repair and prevents cell division if there is heavy damage, therefore halting development of the tumour.
- p53 regulates cell-cycle arrest, apoptosis, DNA repair, cellular senescence, and angiogenesis, in response to cellular stress,
DNA Repair Genes
- These genes ensure accurate DNA copying during cell division.
- Mutations in DNA repair genes increase the frequency of mutations in other genes (TSG and oncogenes).
- Defects in DNA repair systems (mismatch repair, nucleotide excision repair, recombination repair) contribute to various cancers.
- Breast cancer susceptibility genes (BRCA1 and BRCA2) and hereditary non-polyposis colon cancer genes are examples of DNA repair genes.
Mechanisms in Carcinogenesis
- A long period of time passes between stimulus exposure and the development of clinical cancer.
- Different stages: Initiation, Promotion, Progression
- Factors like genetic factors, DNA repair, local tissue response, immune response impact stimulus-effect during carcinogenesis.
- Tumour development is an accumulation of alterations, not just a single gene change.
Hallmarks of Cancer
- Key characteristics of cancer: Evading apoptosis, self-sufficiency in growth signals, insensitivity to anti-growth signals, tissue invasion & metastasis, sustained angiogenesis, and limitless replicative potential.
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Description
Explore the key factors influencing tumour development in this quiz on Neoplasia III. Learn about the roles of intrinsic and extrinsic factors, including genetic mutations and inherited conditions that predispose individuals to various tumours. Understand how DNA repair mechanisms play a critical role in preventing tumour formation.
