TY - JOUR T1 - Individual and family characteristics associated with protein truncating <em>BRCA1</em> and <em>BRCA2</em> mutations in an Ontario population based series from the Cooperative Family Registry for Breast Cancer Studies JF - Journal of Medical Genetics JO - J Med Genet SP - e91 LP - e91 DO - 10.1136/jmg.40.8.e91 VL - 40 IS - 8 AU - H Ozcelik AU - J A Knight AU - G Glendon AU - H Yazici AU - N Carson AU - P J Ainsworth AU - S A M Taylor AU - H Feilotter AU - R F Carter AU - N F Boyd AU - I L Andrulis Y1 - 2003/08/01 UR - http://jmg.bmj.com/content/40/8/e91.abstract N2 - Studies using multicase breast cancer families led to the mapping and eventual cloning of the two susceptibility genes for breast or ovarian cancer or both, BRCA1(MIM 113705) and BRCA2 (MIM 600185).1,2 In early studies attempting to characterise the clinical impact of mutations in these genes, investigators continued to analyse large multicase families.3 More recently, groups have focused on patients with breast cancer unselected for strong family cancer history to make their findings more generally applicable.4–7 With the broadening of study participant ascertainment, there has been a drop in the estimates of lifetime breast cancer penetrance attributable to BRCA1 and BRCA2 from greater than 80% initially to values as low as 40%.3,8Attempts to characterise the range and frequency of BRCA1 and BRCA2 mutations in breast cancer families have also been complicated by the different molecular techniques used to identify them. Owing to the large size, multiexonic nature, and lack of any universally identified mutational hot spots in the genes, few studies have conducted a thorough investigation of the presence of mutations in both genes. Also, there have been some missense mutations of unknown clinical significance identified (Breast Cancer Information Core). There is also some evidence that the position of the mutation in the BRCA2 gene may influence the clinical manifestation of cancer risk, which would further complicate the interpretation of findings from studies that use targeted molecular analysis.9Molecular studies of cases ascertained through a population based design more accurately reflect the range and frequency of BRCA1 and BRCA2 mutations in a specific population. The Ontario Familial Breast Cancer Registry (OFBCR)10,11 is one of six sites participating in the international Cooperative Family Registry for Breast Cancer Studies (CFRBCS). The OFBCR is a population based breast cancer registry, the purpose … ER -