Question

Agents causing cancer can be classified into 3 broad groups: Radiation, chemical compounds or microbiological organisms. Briefly explain each of these classes giving examples of how each of them might cause cancer.

List 5 examples each of oncogenes and tumor suppressor genes, and state the tumors associated with each of the examples.

Answer 1

ANS: 1st Part

Any agent that cause or promote cancer is termed as Carcinogen. This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. There are manly three major group of Carcinogen's,

(a) Radiation: Radiation of certain wavelengths, called ionizing radiation, has enough energy to damage DNA and cause cancer. Ionizing radiation includes radon, x-rays, gamma rays, and other forms of high-energy radiation.These forms of radiation can be released in accidents at nuclear power plants and when atomic weapons are made, tested, or used.Low-level ionizing radiation may induce irreparable DNA damage leading to pre-mature aging and cancer.

Examples:

(i) Radon is a radioactive gas released by rocks and soil, formed when the radioactive element radium breaks down. People who are exposed to high levels of radon have an increased risk of lung cancer.

(ii) Ultraviolet radiations from sunlight is the most common cause of skin cancer.

(b) Chemical Compounds:Chemical carcinogens can target certain genes termed proto-oncogenes and tumor suppressor genes, which when become mutated, allow cells to grow without control like in breast, colon and lung cancers. Carcinogenic chemicals can initiate and/or promote cancer by affecting the expression and activity of certain genes responsible for cell growth, differentiation, DNA repair, cell-cycle control, and apoptosis. Some compounds interact directly with DNA, while others are activated to reactive molecules that can bind with DNA by covalent adducts causing mutations in genes crucial to biological processes.

Examples:

(i) Potent carcinogens found in cigarette smoke include polycyclic aromatic hydrocarbons, a Genotoxins which binds directly to DNA causing cancer.

(ii)Asbestos is a genotoxic agent that can induce direct DNA damage, gene transcription, and protein expression important in modulating cell proliferation, cell death, and inflammation.

(c) Microbiological Organism:Many microbes, including viruses, bacteria, and helminths, have been implicated in the causation of cancers. One such microbe, bacteria can cause cancer by two mechanisms: induction of chronic inflammation and production of carcinogenic bacterial metabolites.These microbiological organism generally persist in their hosts for long periods (years or longer). Acute infections may be resolved but also may leave scars that promote neoplasia.

Examples:  Human papilloma viruses; causing anogenital cancers, Helicobacter pylori causing gastric cancers, and hepatitis B and C viruses.

ANS: 2nd Part

Five examples and the corresponding tumor associated with Tumor Suppressor Genes are:

1.RB1 gene - Retinoblastoma

2. P53 gene-  Li Fraumeni syndrome

3. BRCA1/BRCA2 genes - Breast Cancer

4. APC gene- Familial adenomatous polyposis(colon Cancer)

5. PTEN gene- Cowden syndrome

Five examples and the corresponding tumor associated with Oncogenes are:

1. Ras protein - Adenocarcinomas of the pancreas and colon, thyroid tumors, and myeloid leukemia.

2. myc gene - Breast cancer, pancreatic cancer, retinoblastoma, and small cell lung cancer.

3.Raf kinase, and cyclin-dependent kinases - Malignant melanoma, papillary thyroid cancer, colorectal cancer, and ovarian cancer.

4.c-Sis -  Fibrosarcomas, osteosarcomas, breast carcinomas, and melanomas.

5. EGFR,PDGFR&VEGFR -Breast cancer, gastrointestinal stromal tumours, non-small-cell lung cancer and pancreatic cancer.