Angelina Jolie

1. Angelina Jolie The White Coat Wonder

2. Rational • The purpose of our research is to enrich the Premed-A community with the knowledge of other cancers caused by genetic factors, relating specific biological functions affected by these cancers to genetic interactions seen in the presence a BRCA-1 mutation, or other inherited cancer causing genes.

3. BRCA1 and BRCA2 • Both BRCA1 and BRCA 2 are genes that produce tumor suppressor proteins which help in the repair of damaged DNA in the body. • An alteration to one of these genes affect the function or production of the proteins, which will cause damaged DNA to stay untreated.

5. Statistics • Mutations on BRCA1 and BRAC2 result in an increase risk to breast and ovarian cancer for females, account for 20%-25% of hereditary breast cancers. • There is a 50% chance of inheriting the mutated gene from a parent who possesses the mutated gene, and yes, males are at risk of being diagnosed with a mutated gene.

6. Li-Fraumeni Syndrome • Li-Fraumeni syndrome is a rare disorder caused by a genetic mutation on the CHEK2 and TP53 genes, resulting in a higher risk for developing many types of cancers. • Li-Fraumeni is more common in children and young adults, affecting 400 people for ever 64 families.

8. TP53 and CHEK2 • The mutation of TP53, a tumor suppressor gene, seizes in helping cells grow and divide. Due to this uncontrollable division, cells are likely to form tumors. • CHEK2, a tumor suppressor gene, which when appearing in the mutated form causes Li-Fraumeni along with increasing the risk of other cancers such as breast cancer.

9. Retinoblastoma • Retinoblastoma, RB, is a childhood cancer that develops in the retina, where there is specialized light sensitive tissue at the back of the light that is responsible for light and color.

11. RB1 • Mutations in the RB1 gene are inherited in an autosomal dominant pattern. • The RB gene is located on the long arm of chromosome 13, playing a role in growth and development. • The way the gene functions is similar to BRCA 1 and BRCA 2, so once they are mutated, they lead to cancer.

12. Lynch Syndrome • Lynch Syndrome is an autosomal dominant genetic condition of the digestive tract, also known as hereditary non-polyposis colorectal cancer (HNPCC), which increases the risk of colon cancer as well as many other cancers

14. MLH1, MSH2, MSH6, and PMS2 • The MLH1, MSH2, MSH6, and PMS2 genes are responsible for repairing mistakes that occur during the process of DNA replication, so when those genes are mutated, the proper repair of DNA replication mistakes are prevented. As these mutated cells continue to divide, the collected mistakes can lead to an uncontrolled cell growth and possibly cancer.

15. Similarities • All the possible inherited cancers mentioned are similar for the following reasons. • 1. All the inherited cancers have mutated genes that are autosomal dominant genetic conditions. • 2. The genes related are tumor suppressors. • 3. The mutation of the gene seizes the repair of damaged DNA in the body, resulting in tumors.

16. Questions • 1. Given that both genders are equally affected by Lynch Syndrome, and that tumor suppressor genes are mutated in both diseases, why are women more susceptible to breast cancer (mutation of BRCA 1/BRCA 2) over men, other than the reason of differing estrogen levels in both genders? • 2. Is it possible to reverse a mutated gene and bring it back to its original function?

17. Citations • http://www.ambrygen.com/tests/retinoblastoma • http://www.medscape.com/viewarticle/491384_2 • http://ghr.nlm.nih.gov/condition/retinoblastoma • http://ghr.nlm.nih.gov/condition/li-fraumeni-syndrome • http://p53.free.fr/Database/p53_cancer/p53_germline.html • http://www.cancer.org/cancer/ovariancancer/detailedguide/ovarian-cancer-what-causes • http://www.cancer.net/cancer-types/lynch-syndrome • http://ghr.nlm.nih.gov/condition/lynch-syndrome