AIIMS Nov 2006 - Pre Clinical MCQ Answer 32

Answer: Ataxia Telangiectasia

Review:

BRCA1 and BRCA2 are major genes related to hereditary breast cancer. People who have inherited certain mutations in these genes have a high risk of developing breast cancer, ovarian cancer, and several other types of cancer over their lifetimes. Men with BRCA1 mutations have an increased risk of developing prostate cancer. Mutations in the BRCA2 gene are associated with an increased chance of developing male breast cancer and cancers of the prostate, pancreas, gallbladder, bile duct, and gastrointestinal tract.

Melanoma (an aggressive form of skin cancer) and lymphoma (a cancer of immune system cells) also are more common among people who have BRCA2 mutations.
Inherited changes in several other genes, including ATM, CHEK2, and RAD51, have been associated with an increased risk of breast cancer. Although some research suggests that certain versions of the AR gene also may be associated with breast cancer risk, several other studies have not shown this connection.
Other gene mutations are acquired during a person's lifetime and are present only in certain cells. These changes, which are called somatic mutations, are not inherited. Somatic mutations in the ERBB2 (also called Her-2/neu), DIRAS3 (formerly ARHI), and TP53 genes have been identified in some cases of breast cancer.


The risk for breast cancer is increased with Li-Fraumeni syndrome (LFS), a genetic autosomal dominant cancer syndrome. A diagnosis of LFS is made when all of the following characteristics are present in a family:

• sarcoma <45>and
  
  
• a first degree relative with cancer <45>and
  
  
• a first or second degree relative with cancer <45>

The majority of LFS (about 70 percent) is caused by mutations in a gene on chromosome 17 known as p53. Mutations in p53 confer an increased risk for early onset breast cancer, childhood sarcoma, osteosarcoma, brain tumors, leukemia, and adrenocortical carcinoma. Persons with a p53 mutation have a 50 percent chance of developing one of the associated cancers by age 50. For women, the risk of breast cancer specifically is 49 percent by age 44 with a lifetime risk of 60 percent.


(Ref: http://cancer.stanford.edu/information/geneticsAndCancer/types/lifrmni/)


Overall, the risk of an Ataxia Telangiectasia patient developing any cancer is 37-fold higher than individuals in the general population. The risk of developing lymphoid tumors, however, the most frequently diagnosed cancers in A-T patients, is 100-fold higher than in the general population; A-T patients have about a 10 percent risk of developing lymphoma or leukemia. Cancers also occur in the stomach, brain, ovary, skin, liver, larynx, parotid gland, and breast.

(Ref: http://www.cancer.gov/cancertopics/factsheet/ataxiaqa)

Category: AIIMS Nov 2006 MCQs