Genetic predisposition to breast cancer: past, present, and future.
In recent years, our understanding of genetic predisposition to breast cancer has advanced significantly. Three classes of predisposition factors, categorized by their associated risks of breast cancer, are currently known. BRCA1 and BRCA2 are high-penetrance breast cancer predisposition genes identified by genome-wide linkage analysis and positional cloning. Mutational screening of genes functionally related to BRCA1 and/or BRCA2 has revealed four genes, CHEK2, ATM, BRIP1, and PALB2; mutations in these genes are rare and confer an intermediate risk of breast cancer. Association studies have further identified eight common variants associated with low-penetrance breast cancer predisposition. Despite these discoveries, most of the familial risk of breast cancer remains unexplained. In this review, we describe the known genetic predisposition factors, expound on the methods by which they were identified, and consider how further technological and intellectual advances may assist in identifying the remaining genetic factors underlying breast cancer susceptibility.
Turnbull
Clare
C
Section of Cancer Genetics, Institute of Cancer Research, Sutton, SM2 5NG, United Kingdom. clare.turnbull@icr.ac.uk
Rahman
Nazneen
N
D000091162:AMP-Activated Protein Kinase Kinases; D017766:Acid Anhydride Hydrolases; D015703:Antigens, CD; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics* / Q000628:therapy; D015820:Cadherins / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics; D064447:Checkpoint Kinase 2; D045643:DNA Repair Enzymes / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D000076164:Fanconi Anemia Complementation Group N Protein; D051856:Fanconi Anemia Complementation Group Proteins; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019683:Penetrance; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D020365:RNA Helicases / Q000235:genetics; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D000076164:Fanconi Anemia Complementation Group N Protein; D051856:Fanconi Anemia Complementation Group Proteins; D009687:Nuclear Proteins; C512790:PALB2 protein, human; D025521:Tumor Suppressor Proteins; D064447:Checkpoint Kinase 2; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D017766:Acid Anhydride Hydrolases; C112158:RAD50 protein, human; C000618935:BRIP1 protein, human; D020365:RNA Helicases; D045643:DNA Repair Enzymes