title: Recurrent CYP2C19 deletion allele is associated with triple-negative breast cancer.
abstract: BACKGROUND
  Using a genome-wide approach, we have previously observed an increase in the frequency of rare copy number variants (CNVs) in familial and early-onset breast cancer cases when compared to controls. Moreover, the biological networks of the CNV disrupted genes differed between the two groups. Here, six of the previously observed CNVs were selected for further investigation. Four of these were singletons and disturbed the following genes: DCLRE1C, CASP3, DAB2IP and ITGA9, encoding proteins that are part of the TP53 and β-estradiol centered network. The two others were recurrent alleles and disrupted CDH19 and CYP2C19 genes. Of these, CDH19 encodes a cadherin functioning as a cell-cell adhesion receptor and CYP2C19 a CYP450 enzyme with a major function in estrogen catabolism.
  
  
  METHODS
  The exact breakpoints of the six previously observed CNV deletion alleles were defined by using qPCR, nested PCR and sequencing. The prevalence of these CNVs was investigated in 842 Northern Finnish breast cancer cases, unselected for family history of cancer and age at disease onset, as well as in 497 healthy female controls by using multiplex PCR. Also the association of the relatively common CDH19 and CYP2C19 deletion alleles with different clinical parameters was studied.
  
  
  RESULTS
  No significant differences in the carrier frequencies between cases and controls were found for any of the studied CNVs. However, the deletion in CYP2C19 showed a significant association with triple-negative breast cancer (p=0.021).
  
  
  CONCLUSIONS
  Our results indicate that inherited changes in CYP2C19 gene participating in estrogen catabolism have an influence on the molecular subtype of breast cancer.
authors.forename: Anna
authors.initials: A
authors.lastname: Tervasmäki
authors.affiliation: Department of Clinical Chemistry and Biocenter Oulu, Laboratory of Cancer Genetics and Tumor Biology, University of Oulu, P,O, Box 5000, Oulu FI-90014, Finland. robert.winqvist@oulu.fi.
authors.forename: Robert
authors.initials: R
authors.lastname: Winqvist
authors.forename: Arja
authors.initials: A
authors.lastname: Jukkola-Vuorinen
authors.forename: Katri
authors.initials: K
authors.lastname: Pylkäs
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics*; D056915:DNA Copy Number Variations; D005260:Female; D006801:Humans; D008875:Middle Aged; D064726:Triple Negative Breast Neoplasms / Q000201:enzymology* / Q000235:genetics*
chemical_list: D065731:Cytochrome P-450 CYP2C19