Forskning
Udskriv Udskriv
Switch language
Rigshospitalet - en del af Københavns Universitetshospital
Udgivet

Cytochrome P-450 2D6 (CYP2D6) Genotype and Breast Cancer Recurrence in Tamoxifen-Treated Patients: Evaluating the Importance of Loss of Heterozygosity

Publikation: Bidrag til tidsskriftReviewForskningpeer review

DOI

  1. Effect estimates in randomized trials and observational studies: comparing apples with apples

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Robust Tests for Additive Gene-Environment Interaction in Case-Control Studies Using Gene-Environment Independence

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Semen Quality as a Predictor of Subsequent Morbidity: A Danish Cohort Study of 4,712 Men With Long-Term Follow-up

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Age at Menarche and Risk of Multiple Sclerosis: A Prospective Cohort Study Based on the Danish National Birth Cohort

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Whole genome sequencing of breast cancer

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  2. Genome-wide association and transcriptome studies identify target genes and risk loci for breast cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Subtypes in BRCA-mutated breast cancer

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Thomas P Ahern
  • Daniel L Hertz
  • Per Damkier
  • Bent Ejlertsen
  • Stephen J Hamilton-Dutoit
  • James M Rae
  • Meredith M Regan
  • Alastair M Thompson
  • Timothy L Lash
  • Deirdre P Cronin-Fenton
Vis graf over relationer

Tamoxifen therapy for estrogen receptor-positive breast cancer reduces the risk of recurrence by approximately one-half. Cytochrome P-450 2D6, encoded by the polymorphic cytochrome P-450 2D6 gene (CYP2D6), oxidizes tamoxifen to its most active metabolites. Steady-state concentrations of endoxifen (4-hydroxy-N-desmethyltamoxifen), the most potent antiestrogenic metabolite, are reduced in women whose CYP2D6 genotypes confer poor enzyme function. Thirty-one studies of the association of CYP2D6 genotype with breast cancer survival have yielded heterogeneous results. Some influential studies genotyped DNA from tumor-infiltrated tissues, and their results may have been susceptible to germline genotype misclassification from loss of heterozygosity at the CYP2D6 locus. We systematically reviewed 6 studies of concordance between genotypes obtained from paired nonneoplastic and breast tumor-infiltrated tissues, all of which showed excellent CYP2D6 genotype agreement. We applied these concordance data to a quantitative bias analysis of the subset of the 31 studies that were based on genotypes from tumor-infiltrated tissue to examine whether genotyping errors substantially biased estimates of association. The bias analysis showed negligible bias by discordant genotypes. Summary estimates of association, with or without bias adjustment, indicated no clinically important association between CYP2D6 genotype and breast cancer survival in tamoxifen-treated women.

OriginalsprogEngelsk
TidsskriftAmerican Journal of Epidemiology
Vol/bind185
Udgave nummer2
Sider (fra-til)75-85
Antal sider11
ISSN0002-9262
DOI
StatusUdgivet - 15 jan. 2017

ID: 52152551