Carcinogenesis and Epigenetics Overview

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Questions and Answers

What type of gene mutation enables a cell to proliferate due to gaining a function?

Antioncogene

Epigenetic regulator

Oncogene (correct)

Tumor suppressor gene

Which of the following describes a gene that loses its function and cannot regulate cell proliferation?

Proto-oncogene

DNA repair gene

Oncogene

Tumor suppressor gene (correct)

What mechanism allows neoplastic cells to evade cell death?

Transcription regulation

Gene amplification

Chromosomal rearrangement

Oncogene activation (correct)

Which term refers to the accumulation of DNA errors due to a failure in correcting mutations?

Genome instability Signup and view all the answers

What is the role of epigenetics in cancer development?

Regulates gene expression without changing DNA sequence Signup and view all the answers

What role does the TET2 enzyme play in relation to DNA methylation?

Facilitates DNA demethylation, particularly in hyperglycemia Signup and view all the answers

In cancer, what is the effect of widespread alterations in DNA methylation patterns?

Encourages tumor-cell heterogeneity and survival Signup and view all the answers

Which of the following best describes the function of histone acetylation?

Promotes an open, active chromatin state for gene expression Signup and view all the answers

What common physiological mechanism is involved in gene silencing?

DNA methylation of cytosines Signup and view all the answers

How does DNA hypermethylation contribute to cancer risk?

By leading to aberrant over-expression of oncogenes Signup and view all the answers

What is the primary significance of the strong correlation between stem cell divisions and cancer risk?

It indicates that more divisions lead to increased DNA methylation changes Signup and view all the answers

Which of the following statements about post-translational histone modifications is true?

Can result in either gene expression activation or silencing Signup and view all the answers

What is the estimated number of cancer cases caused by dental radiography annually in the US?

Approximately 1000 Signup and view all the answers

Which of the following types of HPV is classified as high-risk and is associated with cervical cancer?

HPV-16 Signup and view all the answers

Which mechanism allows high-risk HPV to cause cancer by integrating into host DNA?

Circular DNA breaks to form a linear strand Signup and view all the answers

Which HPV vaccine covers the broadest range of HPV types including high-risk and low-risk strains?

Gardasil 9 Signup and view all the answers

Which cancer is not associated with Epstein-Barr virus (EBV)?

Chronic lymphocytic leukemia Signup and view all the answers

Which cancer is most commonly associated with the use of alkylating agents?

Acute myeloid leukemia Signup and view all the answers

What is the role of promoters in carcinogenesis?

They increase the risk of mutations in already initiated cells. Signup and view all the answers

Which gene polymorphism is associated with increased lung cancer risk among smokers?

CYP1A1 Signup and view all the answers

What is the mechanism by which UVB radiation contributes to skin cancer?

Formation of pyrimidine dimers that distort DNA structure. Signup and view all the answers

How does chronic inflammation contribute to cancer risk?

By promoting cell regeneration and proliferation. Signup and view all the answers

Which type of radiation is NOT filtered out by the ozone layer and is considered carcinogenic?

Ionizing radiation Signup and view all the answers

What is a significant risk factor for developing breast cancer as noted in the 18th century?

Shorter menstrual cycles Signup and view all the answers

Which syndrome is linked to a 16-44 times higher risk of developing MALT lymphoma?

Sjögren syndrome Signup and view all the answers

What characteristic distinguishes UVB radiation from UVA and UVC in terms of carcinogenic potential?

It creates the most significant risk of skin cancer. Signup and view all the answers

Which of the following is a known consequence of long-term exposure to polycyclic hydrocarbons?

Development of acute myeloid leukemia Signup and view all the answers

Study Notes

Carcinogenesis - Mutated Genes

A mutated gene that gains a function and enables a cell to proliferate is likely to be an oncogene
A mutated gene that loses a function and can no longer regulate cell proliferation could be a tumor suppressor gene
A mutated gene that allows a neoplastic cell to escape cell death might be an apoptosis regulator gene
A mutated gene that allows errors in the DNA sequence to go unchecked and accumulate may be a DNA repair gene

Epigenetics: Beyond Genetics

While most cells in the body have the same DNA, they have different functions and identities due to epigenetics, the regulation of gene expression beyond the DNA sequence itself.
Epigenetic mechanisms include:
- DNA Hypermethylation and Demethylation: This can silence important genes for tumor suppression or overexpress oncogenes without changes in the DNA sequence.
- Post-translational Histone Modifications: These can open chromatin and allow gene expression or close chromatin and silence genes.
- Micro RNA: Micro RNA plays a role in gene regulation by silencing target mRNA transcripts.
TET2 enzyme is involved in demethylation and is more potent in hyperglycemia. This link suggests a higher cancer susceptibility for patients with diabetes due to high blood glucose levels.
Stem cells have an average number of divisions that directly correlate to the rate and risk of cancer in that tissue.

Methylation of Cytosines

Methylation of cytosines on DNA is a common physiological mechanism for silencing gene expression.
70-80% of CpGs are methylated in human adult cells.

Post-translational Histone Modifications

Post-translational histone modifications can open chromatin for gene expression or close chromatin for gene silencing.
Histone acetylation leads to an open, active chromatin state.
Histone methylation has more diverse and complex effects.
Cancer cells show widespread alterations in DNA methylation patterns and histone post-translational modifications, leading to aberrant gene expression.

Chronic Inflammation as Promoter

Chronic inflammation, such as in inflammatory bowel disease (IBD), is associated with chronic wound repair and regeneration, increasing the risk of colorectal cancer by 1.5-2 fold.
Sjögren syndrome, a chronic autoimmune disorder, is associated with an increased risk of MALT lymphoma, potentially 16-44 times higher than the general population.
Normal stem cell divisions are another factor that can act as a promoter in carcinogenesis.

Carcinogens and their Cellular Interactions

Chemical carcinogenesis, radiation carcinogenesis, and microbial carcinogenesis all contribute to cancer development.

Radiation Carcinogenesis

Ultraviolet (UV) and ionizing radiation (electromagnetic and particulate) are carcinogenic.
UV radiation, particularly UVB, is responsible for inducing cutaneous tumors. The risk of skin cancer is greater in fair-skinned individuals with lower melanin levels.
UVB is carcinogenic due to the formation of pyrimidine dimers that distort the DNA helix, preventing proper pairing. This can overwhelm the nucleotide excision repair pathway, leading to an accumulation of mutations.
Dental x-rays are a source of low-dose radiation, but proper adherence to safety protocols can significantly reduce the risk of cancer development.

Microbial Carcinogenesis

Several oncogenic DNA viruses, RNA viruses, and bacteria are implicated in carcinogenesis.

Human Papillomavirus (HPV)

HPV is a ubiquitous DNA virus that exclusively infects humans. Over 120 HPV types have been identified, with some classified as high-risk and others as low-risk.
Certain high-risk HPV types integrate into the host DNA, leading to viral overexpression of E6 and E7.
HPV vaccines are available to prevent HPV infection and are recommended for 11-12 year olds.

Epstein-Barr Virus (EBV)

EBV is associated with several cancers, including Burkitt lymphoma, B-cell lymphomas in immunocompromised patients, Hodgkin lymphomas, NK/T cell-lymphoma, and nasopharyngeal carcinoma.
EBV seems to act as a potent mitogen, promoting cell division.

Hepatitis B and C Viruses (HBV, HCV)

HBV and HCV are responsible for a significant portion of hepatocellular carcinoma worldwide.
The dominant oncogenic effect of HBV and HCV is likely due to the immune-mediated chronic inflammation and liver regeneration.

Helicobacter pylori

H. pylori infection increases the risk of duodenal and gastric ulcers, gastric adenocarcinoma, and MALT lymphoma.
The pro-carcinogenic effect of H. pylori is attributed to the chronic inflammatory state it creates.

Cancer and Immunosuppression

Immunodeficiency states are associated with an increased frequency of cancer.
This is due to decreased immune surveillance, which is the process of detecting and destroying abnormal cells.
When the immune system is compromised, the body can't properly fight tumor cells and infections.
MHC I antigen processing is crucial in immune surveillance as it presents endogenous/self antigens to CD8+ (cytotoxic) T-cells, ensuring the destruction of cells with abnormal antigens.

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Description

This quiz explores the crucial concepts of carcinogenesis, including the roles of oncogenes, tumor suppressor genes, and apoptosis regulators. Additionally, it delves into epigenetics, emphasizing how gene expression is regulated beyond the DNA sequence. Test your knowledge on the molecular mechanisms that underpin cancer development and regulation.