title: A novel duplication polymorphism in the FANCA promoter and its association with breast and ovarian cancer.
abstract: The FANCA gene is one of the genes in which mutations lead to Fanconi anaemia, a rare autosomal recessive disorder characterised by congenital abnormalities, bone marrow failure, and predisposition to malignancy. FANCA is also a potential breast and ovarian cancer susceptibility gene. A novel allele was identified which has a tandem duplication of a 13 base pair sequence in the promoter region.
  
  
  METHODS
  We screened germline DNA from 352 breast cancer patients, 390 ovarian cancer patients and 256 normal controls to determine if the presence of either of these two alleles was associated with an increased risk of breast or ovarian cancer.
  
  
  RESULTS
  The duplication allele had a frequency of 0.34 in the normal controls. There was a non-significant decrease in the frequency of the duplication allele in breast cancer patients. The frequency of the duplication allele was significantly decreased in ovarian cancer patients. However, when malignant and benign tumours were considered separately, the decrease was only significant in benign tumours.
  
  
  CONCLUSIONS
  The allele with the tandem duplication does not appear to modify breast cancer risk but may act as a low penetrance protective allele for ovarian cancer.
authors.affiliation: Department of Pathology, Peter MacCallum Cancer Centre, Locked Bag 1 A'Beckett St, Melbourne, Victoria 8006, Australia. ella.thompson@petermac.org
authors.forename: Ella
authors.initials: E
authors.lastname: Thompson
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Dragovic
authors.forename: Sally-Anne
authors.initials: SA
authors.lastname: Stephenson
authors.forename: Diana M
authors.initials: DM
authors.lastname: Eccles
authors.forename: Ian G
authors.initials: IG
authors.lastname: Campbell
authors.forename: Alexander
authors.initials: A
authors.lastname: Dobrovic
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D052217:Fanconi Anemia Complementation Group A Protein / Q000235:genetics*; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008957:Models, Genetic; D010051:Ovarian Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011401:Promoter Regions, Genetic; D012306:Risk
chemical_list: C498471:FANCA protein, human; D052217:Fanconi Anemia Complementation Group A Protein