Question

Genetics

Examine how mutations in the DNA lead to tumor formation and metastasis.

Explain the “two-hit hypothesis” in the development of cancer.

Examine the role of cell cycle checkpoints and the development of cancer.

If cancer, is a genetic disease, what role do environmental factors play in the cancer process?

Discuss how you would explain to a patient how radiation; which is known to cause mutations and cancer, is also a viable treatment option.

Answer 1

1 Cancer is a hereditry disease.Any changes to genes that control our function ,deviate the cell from growing normally and become cancerous.Often these types of genes ,sometimes it may be present in the germ cells which is the reproductive cells of the body,resulting in germ line changes and this will be found in every cell of the off springs.Due to exposure to carcinogenic substances which damage DNA such as tobacco smoke and radiation,UV rays from Sun result in cells to divide abnormally.Initially it affects one unit of DNA ie nucleotide resulting in replacement of one nucleotide with another .Sometimes there will be rearrangements,deletions or duplications of DNA.Therefore DNA alterations can addect the structure and functionof the proteins corresponding to it.These effects can change a cells behaviour fom normal to abnormal.There are different kind of mutations found in cancer cells which include Missense mutation,Nonsense mutation,Frameshift mutation and Chromosome Rearrangements.

Missense mutation occurs when a change in the aminoacid sequence occurs resulting in the change of a single DNA.Nonsense mutation is a DNA change which creates stop codon and eliminates translation.Chromosome rearrangements occurs when a piece of chromosome breaks resulting in deletion,translocation and finally inversion or duplication takes place.Frameshift mutation occurs when a DNA base is added or removed ,shifting the DNA as well as aminoacid sequence.

2 Two hit hypothesis was proposed by Alfred Knudson.it is otherwise known as multiple-hit hypothesis.Tumor suppressor genes undergo a variety of mutations and the loss-of function mutation that occur in tumor suppressive genes are recessive in nature.Furthermore for a cell to become cancerous ,both of the cells tumor suppressor genes must be mutated.According to Knudson multiple hits to DNA are necessary to cause cancer.

3 Daughter cells should always be the replica of the parent cell.Any mistakes in the duplication of the chromosomes lead to mutations,these may be passed forward to each and every new cell,that is produced from an abnormal cell.Inorder to prevent an abnormal cell from dividing there are some internal control mchanisms that operate at the three main cycle checkpoints..These checkpoints occur near the the end of G1.it is the G1 checkpoint that determines whether all conditions are favourable for cell division to proceed.There is also a check for genomic DNA damage at the G1 check point.if it does not follow the requirements will not be allowed to go to S phase.The G2 bars entry into the mitotic phase if conditions are not met.The main function is to ensure that all of the chromosomes are replicated and the replicated DNA is not damaged.The M check point occurs at the end of metaphase stage of karyokinesis because it determines whether all the chromatids are attached to the spindle microtubules.Cancer comprises many different diseases by a common mechanism ie uncontrolled cell growth.All cancer initialy start when a gene mutation give rise to a faulty protein.Even minor mistakes result in more subsequent mistakes.More and more uncorrected errors are passed from the parent cell to the daughter cells and amplified as each generation produces more non-functional proteins from uncorrected DNA damage.The uncontrolled growth of the mutated cells outspae the growth of normal cells and result in a tumor.

4Environmental factors are chemical carcinogen which include industrial chemicals,drugs and tobacco,physical carcinogen include ionizing radiation,ultraviolet tradiation,chronic irritation and tissue trauma ,viral carcinogen are virus capable of causing cancer are known as oncovirus such as Epstein barr virus ,hepatitis B virus and human papilloma virus and helicobacter pylori infection is associated with an increased risk of gastric cancer.