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Mutations and Disease Associations

Five Major Diseases (3)
  1. Xeroderma pigmentosum
  2. Non small Cell Lung Cancer
  3. Colorectal Neoplasms
  4. Breast Cancer
  5. Small Cell Carcinoma
Major Mutations
Xeroderma pigmentosum
Mutations take place in exons 3 and 4 as well as intron 3. The mutations were deletions and splice site mutations that resulted in frameshifts within the DNA binding site. (30)
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Non small Cell Lung Cancer
A common mutation is the tyrosine kinase enzyme, as well as its ligand, the ephrin receptor protein. (31)
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Colorectal Neoplasms
Can be caused by mutations to the APC, MSH2, MLH1, PMS1, PMS2, MSH6, TGFBR2, and MLH3 genes. (32)
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Breast Cancer
The most common mutations are of the BRCA1 and BRCA2 genes. (33)
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Small Cell Carcinoma
Mutations were observed in histone modifier genes CREBBP, EP300, and MLL, as well as tyrosine kinase genes PTEN, SLIT2, and EPHA7. (35)
Most Common Diseases 
Xeroderma pigmentosum
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Xeroderma pigmentosum is an autosomal recessive disorder that results in extreme sensitivity to ultraviolet light. This condition leaves affected individuals extremely susceptible to sunburns on any exposed skin, often resulting in freckles covering most of their skin. Repeated exposure to sunlight can also cause dry skin and darkening of the skin. The lack of XPA DNA repair proteins means many of those affected by xeroderma pigmentosum will develop skin cancer over the course of their life. Xeroderma pigmentosum also causes significant issues in the eyes, resulting in anything from pain and irritation up to clouding of the cornea. (30)
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Xeroderma pigmentosum is an autosomal recessive disorder, meaning that it is incredibly difficult to pass on to offspring. Both parents need to be either carriers or affected by the disorder. The disorder is also very rare, affecting only roughly 1 in 1,000,000 people in America and Europe. Xeroderma pigmentosum is incurable, but the symptoms are manageable. The easiest way to manage symptoms is simple prophylaxis, avoiding the sun or using high spf sunblock. The other symptoms are much more difficult to treat, especially the many types of skin cancer common to sufferers of xeroderma pigmentosum. (30)
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Non-Small Cell Lung Cancer
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Non-small cell lung cancer is the most common form of lung cancer, constituting 85% of all lung cancer diagnosis worldwide. It also is the deadliest form of cancer, causing more deaths than any other form of cancer. It is also the type of lung cancer that is less likely to be caused by smoking, the dominant being small cell lung cancer. Non small cell lung cancer is likely to be genetically linked. Children of people with parents who have non-small cell lung cancer are up to three times as likely to develop non-small cell lung cancer. (31) Cancer is very common in those who have malfunctioning XPA genes. XPA is a DNA repair protein and, without it, DNA can become irreparably damaged. This can lead to tumors, masses of cells that grow abnormally and without end. The treatment for lung cancer is similar to that of most other cancers. Radiation, chemotherapy, and surgery are the main avenues of treatment. These unfortunately cannot treat the underlying cause of cancer caused by XPA since none of these will repair damaged DNA. (31)
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