Susceptibility to Inheritance Genetic Susceptibility to Cancer California State University, Stanislaus  Figures Susceptibility to Inheritance Susceptibility to cancers is inherited when a “gene mutation is present in the egg or sperm that formed the child.” (#3) Cancers that run in the family are most often due to damaged tumor repressor genes. These genes no longer utilize apoptosis to prevent uncontrolled cell growth in cells with potentially damaged DNA and allow cancer to develop Genes that function as tumor suppressors, also known as tumor suppressor genes (TSG), slow down cell division. When there is a mutation of this gene, cells may grow out of control and develop tumors. The inherited faulty tumour suppressor genes (TSG) are a common cause of autosomal dominantly inherited susceptibility to specific cancers. A large number of inherited cancer susceptibility conditions are due to the inheritance of faulty TSG, and the inactivation of the normal allele in the susceptible tissue is usually the rate-limiting step to the initiation of a tumour in such individuals. Li-Fraumeni Syndrome Li-Fraumeni syndrome increases an individual’s risk of developing cancers, such as breast cancer, brain tumors, and a bone cancer, osteosarcoma. The two genes associated with this condition, TP53 and CHEK2, are both tumor suppressor genes. The tumor protein gene, TP53, normally binds to DNA, which then causes another protein, p21, to be produced. The p21 protein acts as a stop signal for cell division. Mutations in either gene allow cells to divide uncontrollably and form tumors. This is a rare familial disorder mainly seen in children and young adults that is inherited in an autosomal dominant pattern Inherited Cancers Breast Cancer: It has been recently discovered that there are genes related to the susceptibility of breast cancer. These genes are called BRCA1, BRCA2. “About 80% of the hereditary breast cancer” is closely related to BRCA1 and BRCA2. (Xu 2012) BRCA1 and BRCA2 are genes involved in the “process of DNA damage repair, transcriptional regulation, cell cycle regulation and other important pathway to inhibit tumor” (Xu 2012) Women with the BRCA1 and BRCA2 gene mutations are at risk of about 87% of developing breast cancer. Ovarian Cancer: Three types of hereditary ovarian cancer have been recognized: "site-specific", breast and ovarian cancer syndrome, and nonpolyposis colorectal cancer. Interestingly, the first two types are related to germ line mutations in the same two tumor suppressor genes responsible for breast cancer (BRCA1 and BRCA2); modifications in these genes are accountable for 90% of hereditary ovarian cancer cases. The third type, nonpolyposis colorectal, is a cancer not necessarily limited to ovaries, but is responsible for the other 10% of hereditary ovarian cancers and has been linked to germ line mutations in DNA mismatch repair genes, especially hMLH1 and hMSH2. Introduction A cancer susceptibility gene is an inherited gene mutation that makes a cancer more likely to develop. In many cancers, it’s thought that about 5–10% of cases (between 5 and 10 out of every 100 cases) may be linked to inherited genes. Scientists have discovered cancer susceptibility genes for some of the more common cancers that can run in families, such as cancers of the breast, bowel, ovary and womb. Figure 1: Tumor-suppressor gene vs. Mutated tumor-suppressor gene Figure 2: Tumor Protein gene 53 Authors Emily Celey-Butlin1, Mohammad Nourian1, Kristina Kozlov1, Nicole Mapa1, Anna Hoppe1 Department of Biological Sciences, California State University, Stanislaus, Turlock, CA 95382, United States References Clinical implications for BRCA gene mutation in breast cancer. Molecular Biology Reports, 2012, Volume 39, Number 3, Page 3097. Jin Xu, Baosheng Wang, Yanjun Zhang, Show All (6) Ruihui Li, Yuehua Wang, Shaokun Zhang Mechanisms of inherited cancer susceptibility. Shirley Hodgson. J Zhejiang Univ Sci B. 2008 January; 9(1): 1–4. doi: 10.1631/jzus.B073001 Russo, A. Calò, V. Bruno, L. Rizzo, S. Bazan, V. Di Fede, G. January 2009. Hereditary Ovarian Cancer. Critical Reviews in Oncology/Hematology. 69 (1). Pages 28-44. I