Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. Comprehensive Study of the Clinical Phenotype of Germline BAP1 Variant-Carrying Families Worldwide

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Evaluation of Polygenic Risk Scores for Breast and Ovarian Cancer Risk Prediction in BRCA1 and BRCA2 Mutation Carriers

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Height and Breast Cancer Risk: Evidence From Prospective Studies and Mendelian Randomization

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Immune Regulation by Self-Recognition: Novel Possibilities for Anticancer Immunotherapy

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Breast cancer survival in Nordic BRCA2 mutation carriers-unconventional association with oestrogen receptor status

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. MicroRNA Biomarkers in IBD-Differential Diagnosis and Prediction of Colitis-Associated Cancer

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  3. Polygenic risk scores and breast and epithelial ovarian cancer risks for carriers of BRCA1 and BRCA2 pathogenic variants

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  • Huong D Meeks
  • Honglin Song
  • Kyriaki Michailidou
  • Manjeet K Bolla
  • Joe Dennis
  • Qin Wang
  • Daniel Barrowdale
  • Debra Frost
  • Lesley McGuffog
  • Steve Ellis
  • Bingjian Feng
  • Saundra S Buys
  • John L Hopper
  • Melissa C Southey
  • Andrea Tesoriero
  • Paul A James
  • Fiona Bruinsma
  • Ian G Campbell
  • Annegien Broeks
  • Marjanka K Schmidt
  • Frans B L Hogervorst
  • Matthias W Beckman
  • Peter A Fasching
  • Olivia Fletcher
  • Nichola Johnson
  • Elinor J Sawyer
  • Elio Riboli
  • Susana Banerjee
  • Usha Menon
  • Ian Tomlinson
  • Barbara Burwinkel
  • Ute Hamann
  • Frederik Marme
  • Anja Rudolph
  • Ramunas Janavicius
  • Laima Tihomirova
  • Nadine Tung
  • Judy Garber
  • Daniel Cramer
  • Kathryn L Terry
  • Elizabeth M Poole
  • Shelley S Tworoger
  • Cecilia M Dorfling
  • Stig E Bojesen
  • Henrik Flyger
  • Anne-Marie Gerdes
  • Thomas V O Hansen
  • Susanne K Kjaer
  • Claus Hogdall
  • Estrid Hogdall
  • EMBRACE
Vis graf over relationer

BACKGROUND: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers.

METHODS: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided.

RESULTS: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-) (6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed.

CONCLUSIONS: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations.

OriginalsprogEngelsk
TidsskriftJournal of the National Cancer Institute
Vol/bind108
Udgave nummer2
Sider (fra-til)djv315
ISSN0027-8874
DOI
StatusUdgivet - feb. 2016

ID: 45842442