Identification of new genes associated with breast and ovarian cancer risk. Advances of BCAC, CIMBA and OCAC

Abstract

Breast and ovarian cancers belong to the most common malignancies diagnosed in women. The major inherited susceptibilities to breast and ovarian cancers are germline mutations in either BRCA1 or BRCA2 which however, explain only small number of breast and ovarian cancer cases. Data suggest that majority breast and ovarian cancers are caused by low or moderate penetrance gene mutations. Identification of such mutations provides cancer risk assessment and will help in prophylactic, early diagnosis and treatment. In 2005 three international multidisciplinary consortia have been initiated: Breast Cancer Association Consortium (BCAC), Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and Ovarian Cancer Association Consortium (OCAC) which are forums of investigators from centers over the world, including International Hereditary Cancer Center in Szczecin. The aim of these consortia’s is to combine data from many studies, to provide a reliable assessment of the breast and ovarian cancer risks associated with different genetic and environmental factors, and to identify potential modifiers of cancer risk in carriers of BRCA1 and BRCA2 mutation. BCAC includes 54 centers (table ​(table1)1) over the world and focuses on identification of genes associated with breast cancer risk. Table 1 Centers collaborating in BCAC Currently, BCAC database includs demographic, clinical and epidemiological data from 73,000 breast cancer patients and 80,000 unaffected women. Up to now, 125 genetic alterations (SNPs) localized in different genes have been examined. These SNPs have been selected based on its positive association with breast cancer risk detected in preliminary analyses or Genome-Wide Association Study (GWAS). Results have been presented in 12 manuscripts published in high impact journals, e.g. J Natl Cancer Inst, Nature and Nat Genet (http://www.srl.cam.ac.uk/consortia/bcac/pubs/pubs.html). Ten SNPs have been found to be associated with breast cancer risk overall or by clinical and pathological characteristics (table ​(table22). Table 2 BCAC SNPs associated with breast cancer risk overall or by clinical and pathological characteristics CIMBA database contains demographic, clinical and epidemiological data from 15,700 BRCA1 and 8,600 BRCA2, mutation carriers including 12,700 breast cancer patients, 2,500 ovarian cancer patients and 9,100 unaffected patients from 42 centers over the world (table ​(table33). Table 3 Centers collaborating in CIMBA Results have been presented in 9 manuscripts published in high impact journals, e.g. Am. J Hum Genet, Hum Mol Genet (http://www.srl.cam.ac.uk/consortia/cimba/pubs/pubs.html). Six SNPs have been found to be associated with breast cancer risk (table ​(table44). Table 4 SNPs associated with breast cancer risk in BRCA1/2 carriers OCAC includes 24 centers over the world and focuses on identification of genes that may be related to the risk of ovarian cancer (table ​(table55). Table 5 Centers collaborating in OCAC Currently, OCAC database includs demographic, clinical and epidemiological data from 22,000 ovarian cancer patients and 18,000 unaffected women. Several genetic alterations (SNPs) localized in different genes have been examined. Results have been presented in 13 manuscripts published in high impact journals, e.g. Nat Genet, Cancer Res, In J Cancer (http://www.srl.cam.ac.uk/consortia/ocac/pubs/pubs.html). Seven SNPs have been found to be associated with ovarian cancer risk overall or by clinical and pathological characteristics (table ​(table66). Table 6 SNPs associated with ovarian cancer risk