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Region Hovedstaden - en del af Københavns Universitetshospital
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Genetic predisposition to ductal carcinoma in situ of the breast

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

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  • Christos Petridis
  • Mark N Brook
  • Vandna Shah
  • Kelly Kohut
  • Patricia Gorman
  • Michele Caneppele
  • Dina Levi
  • Efterpi Papouli
  • Nick Orr
  • Angela Cox
  • Simon S Cross
  • Isabel Dos-Santos-Silva
  • Julian Peto
  • Anthony Swerdlow
  • Minouk J Schoemaker
  • Manjeet K Bolla
  • Qin Wang
  • Joe Dennis
  • Kyriaki Michailidou
  • Javier Benitez
  • Anna González-Neira
  • Daniel C Tessier
  • Daniel Vincent
  • Jingmei Li
  • Jonine Figueroa
  • Vessela Kristensen
  • Anne-Lise Borresen-Dale
  • Penny Soucy
  • Jacques Simard
  • Roger L Milne
  • Graham G Giles
  • Sara Margolin
  • Annika Lindblom
  • Thomas Brüning
  • Hiltrud Brauch
  • Melissa C Southey
  • John L Hopper
  • Thilo Dörk
  • Natalia V Bogdanova
  • Maria Kabisch
  • Ute Hamann
  • Rita K Schmutzler
  • Alfons Meindl
  • Hermann Brenner
  • Volker Arndt
  • Robert Winqvist
  • Katri Pylkäs
  • Peter A Fasching
  • Matthias W Beckmann
  • Jan Lubinski
  • Anna Jakubowska
  • Anna Marie Mulligan
  • Irene L Andrulis
  • Rob A E M Tollenaar
  • Peter Devilee
  • Loic Le Marchand
  • Christopher A Haiman
  • Arto Mannermaa
  • Veli-Matti Kosma
  • Paolo Radice
  • Paolo Peterlongo
  • Frederik Marme
  • Barbara Burwinkel
  • Carolien H M van Deurzen
  • Antoinette Hollestelle
  • Nicola Miller
  • Michael J Kerin
  • Diether Lambrechts
  • Giuseppe Floris
  • Jelle Wesseling
  • Henrik Flyger
  • Stig E Bojesen
  • Song Yao
  • Christine B Ambrosone
  • Georgia Chenevix-Trench
  • Thérèse Truong
  • Pascal Guénel
  • Anja Rudolph
  • Jenny Chang-Claude
  • Heli Nevanlinna
  • Carl Blomqvist
  • Kamila Czene
  • Judith S Brand
  • Janet E Olson
  • Fergus J Couch
  • Alison M Dunning
  • Per Hall
  • Douglas F Easton
  • Paul D P Pharoah
  • Sarah E Pinder
  • Marjanka K Schmidt
  • Ian Tomlinson
  • Rebecca Roylance
  • Montserrat García-Closas
  • Elinor J Sawyer
Vis graf over relationer

BACKGROUND: Ductal carcinoma in situ (DCIS) is a non-invasive form of breast cancer. It is often associated with invasive ductal carcinoma (IDC), and is considered to be a non-obligate precursor of IDC. It is not clear to what extent these two forms of cancer share low-risk susceptibility loci, or whether there are differences in the strength of association for shared loci.

METHODS: To identify genetic polymorphisms that predispose to DCIS, we pooled data from 38 studies comprising 5,067 cases of DCIS, 24,584 cases of IDC and 37,467 controls, all genotyped using the iCOGS chip.

RESULTS: Most (67 %) of the 76 known breast cancer predisposition loci showed an association with DCIS in the same direction as previously reported for invasive breast cancer. Case-only analysis showed no evidence for differences between associations for IDC and DCIS after considering multiple testing. Analysis by estrogen receptor (ER) status confirmed that loci associated with ER positive IDC were also associated with ER positive DCIS. Analysis of DCIS by grade suggested that two independent SNPs at 11q13.3 near CCND1 were specific to low/intermediate grade DCIS (rs75915166, rs554219). These associations with grade remained after adjusting for ER status and were also found in IDC. We found no novel DCIS-specific loci at a genome wide significance level of P < 5.0x10(-8).

CONCLUSION: In conclusion, this study provides the strongest evidence to date of a shared genetic susceptibility for IDC and DCIS. Studies with larger numbers of DCIS are needed to determine if IDC or DCIS specific loci exist.

OriginalsprogEngelsk
TidsskriftBreast Cancer Research
Vol/bind18
Udgave nummer1
Sider (fra-til)22
ISSN1465-542X
DOI
StatusUdgivet - 17 feb. 2016

ID: 49445302