Gene associated with autosomal dominant breast cancer?
Ans. B. BRCA 1. (Ref. Bailey and Love 26th/pg. 817)The BRCA1 gene has been associated with an increased incidence of breast (and ovarian) cancer and is located on the long arm of chromosome 17 (17q). The gene frequency in the population is approximately 0.0006. It does, however, occur with greater frequency in certain populations such as Ashkenazi Jews, in whom there is often a common (founder) mutation. BRCA2 .is located on chromosome 13q and there is an association with male breast cancer. Women who are thought to be gene carri- ers may be offered breast screening (and ovarian screening in the case of BRCA1, which is known to impart a 50 % lifetime risk of ovarian cancer), usually as part of a research programme, or genetic counselling and mutation analysis. Those who prove to be 'gene positive' have a 50-80 % risk of developing breast cancer, predominantly while premenopausal. Many opt for prophylactic mastectomy.GeneChromosomeAssociated tumourRb12qRetionablastoma, osteosarcomaBRCA-l and 217q, 13qBreast and ovarian cancerAPC5Colonic cancerP5317qMost human cancers, Li-Fraumeni syndromeHereditary cancer occurs in multiple family members due to germline mutations in high-risk genes which are inherited in autosomal dominant pattern. BRCA1 and BRCA2 are two major high-risk genes associated with hereditary breast cancer.Likelihood of genetic mutation with family history.No. of family cases <50 years oldBRCA1 (%)BRCA2 (%)243317134413355544BRCA1 is also associated with ovarian and, to a lesser extent, colorectal and prostate cancer. bBRCA2 is associated with familial male breast cancer.Genetics of breast cancer.The majority of breast cancers are sporadic, occur randomly, and carry somatic genetic alterations. Hereditary cancer occurs in multiple family members due to germline mutations in high-risk genes which are inherited in autosomal dominant pattern. BRCA1 and BRCA2 are two major high-risk genes associated with hereditary breast cancer. Mutations in CHEK2 contribute to a substantial fraction of familial breast cancer. Carriers of TP53 mutations develop Li-Fraumeni syndrome and are at high risk of developing early onset breast cancer, but these mutations are very rare. Susceptibility alleles in other genes, such as PTEN, ATM, STK11/LKB1, and MSH2/MLH1 are also very rare causes of breast cancer. ~ Devita.
PTEN and KAI
BRCA 1 and 2
APC
P53
Breast