title: Breast cancer risk and 6q22.33: combined results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2.
abstract: Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.
authors: Memorial Sloan-Kettering Cancer Center (MSKCC): Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, New York, New York, United States of America (TK, MG, KO); Department of Environmental Medicine, New York University Cancer Institute, New York University, New York, New York, United States of America (TK), American Cancer Society, Atlanta, Georgia, United States of America (MG).
authors: Tomas
authors: T
authors: Kirchhoff
authors: Mia M
authors: MM
authors: Gaudet
authors: Antonis C
authors: AC
authors: Antoniou
authors: Lesley
authors: L
authors: McGuffog
authors: Manjeet K
authors: MK
authors: Humphreys
authors: Alison M
authors: AM
authors: Dunning
authors: Stig E
authors: SE
authors: Bojesen
authors: Børge G
authors: BG
authors: Nordestgaard
authors: Henrik
authors: H
authors: Flyger
authors: Daehee
authors: D
authors: Kang
authors: Keun-Young
authors: KY
authors: Yoo
authors: Dong-Young
authors: DY
authors: Noh
authors: Sei-Hyun
authors: SH
authors: Ahn
authors: Thilo
authors: T
authors: Dork
authors: Peter
authors: P
authors: Schürmann
authors: Johann H
authors: JH
authors: Karstens
authors: Peter
authors: P
authors: Hillemanns
authors: Fergus J
authors: FJ
authors: Couch
authors: Janet
authors: J
authors: Olson
authors: Celine
authors: C
authors: Vachon
authors: Xianshu
authors: X
authors: Wang
authors: Angela
authors: A
authors: Cox
authors: Ian
authors: I
authors: Brock
authors: Graeme
authors: G
authors: Elliott
authors: Malcolm W R
authors: MW
authors: Reed
authors: Barbara
authors: B
authors: Burwinkel
authors: Alfons
authors: A
authors: Meindl
authors: Hiltrud
authors: H
authors: Brauch
authors: Ute
authors: U
authors: Hamann
authors: Yon-Dschun
authors: YD
authors: Ko
authors: Annegien
authors: A
authors: Broeks
authors: Marjanka K
authors: MK
authors: Schmidt
authors: Laura J
authors: LJ
authors: Van 't Veer
authors: Linde M
authors: LM
authors: Braaf
authors: Nichola
authors: N
authors: Johnson
authors: Olivia
authors: O
authors: Fletcher
authors: Lorna
authors: L
authors: Gibson
authors: Julian
authors: J
authors: Peto
authors: Clare
authors: C
authors: Turnbull
authors: Sheila
authors: S
authors: Seal
authors: Anthony
authors: A
authors: Renwick
authors: Nazneen
authors: N
authors: Rahman
authors: Pei-Ei
authors: PE
authors: Wu
authors: Jyh-Cherng
authors: JC
authors: Yu
authors: Chia-Ni
authors: CN
authors: Hsiung
authors: Chen-Yang
authors: CY
authors: Shen
authors: Melissa C
authors: MC
authors: Southey
authors: John L
authors: JL
authors: Hopper
authors: Fleur
authors: F
authors: Hammet
authors: Thijs
authors: T
authors: Van Dorpe
authors: Anne-Sophie
authors: AS
authors: Dieudonne
authors: Sigrid
authors: S
authors: Hatse
authors: Diether
authors: D
authors: Lambrechts
authors: Irene L
authors: IL
authors: Andrulis
authors: Natalia
authors: N
authors: Bogdanova
authors: Natalia
authors: N
authors: Antonenkova
authors: Juri I
authors: JI
authors: Rogov
authors: Daria
authors: D
authors: Prokofieva
authors: Marina
authors: M
authors: Bermisheva
authors: Elza
authors: E
authors: Khusnutdinova
authors: Christi J
authors: CJ
authors: van Asperen
authors: Robert A E M
authors: RA
authors: Tollenaar
authors: Maartje J
authors: MJ
authors: Hooning
authors: Peter
authors: P
authors: Devilee
authors: Sara
authors: S
authors: Margolin
authors: Annika
authors: A
authors: Lindblom
authors: Roger L
authors: RL
authors: Milne
authors: José Ignacio
authors: JI
authors: Arias
authors: M Pilar
authors: MP
authors: Zamora
authors: Javier
authors: J
authors: Benítez
authors: Gianluca
authors: G
authors: Severi
authors: Laura
authors: L
authors: Baglietto
authors: Graham G
authors: GG
authors: Giles
authors: Amanda B
authors: AB
authors: Spurdle
authors: Jonathan
authors: J
authors: Beesley
authors: Xiaoqing
authors: X
authors: Chen
authors: Helene
authors: H
authors: Holland
authors: Sue
authors: S
authors: Healey
authors: Shan
authors: S
authors: Wang-Gohrke
authors: Jenny
authors: J
authors: Chang-Claude
authors: Arto
authors: A
authors: Mannermaa
authors: Veli-Matti
authors: VM
authors: Kosma
authors: Jaana
authors: J
authors: Kauppinen
authors: Vesa
authors: V
authors: Kataja
authors: Bjarni A
authors: BA
authors: Agnarsson
authors: Maria A
authors: MA
authors: Caligo
authors: Andrew K
authors: AK
authors: Godwin
authors: Heli
authors: H
authors: Nevanlinna
authors: Tuomas
authors: T
authors: Heikkinen
authors: Zachary
authors: Z
authors: Fredericksen
authors: Noralane
authors: N
authors: Lindor
authors: Katherine L
authors: KL
authors: Nathanson
authors: Susan M
authors: SM
authors: Domchek
authors: Niklas
authors: N
authors: Loman
authors: Per
authors: P
authors: Karlsson
authors: Marie
authors: M
authors: Stenmark Askmalm
authors: Beatrice
authors: B
authors: Melin
authors: Anna
authors: A
authors: von Wachenfeldt
authors: Frans B L
authors: FB
authors: Hogervorst
authors: Martijn
authors: M
authors: Verheus
authors: Matti A
authors: MA
authors: Rookus
authors: Caroline
authors: C
authors: Seynaeve
authors: Rogier A
authors: RA
authors: Oldenburg
authors: Marjolijn J
authors: MJ
authors: Ligtenberg
authors: Margreet G E M
authors: MG
authors: Ausems
authors: Cora M
authors: CM
authors: Aalfs
authors: Hans J P
authors: HJ
authors: Gille
authors: Juul T
authors: JT
authors: Wijnen
authors: Encarna B
authors: EB
authors: Gómez García
authors: Susan
authors: S
authors: Peock
authors: Margaret
authors: M
authors: Cook
authors: Clare T
authors: CT
authors: Oliver
authors: Debra
authors: D
authors: Frost
authors: Craig
authors: C
authors: Luccarini
authors: Gabriella
authors: G
authors: Pichert
authors: Rosemarie
authors: R
authors: Davidson
authors: Carol
authors: C
authors: Chu
authors: Diana
authors: D
authors: Eccles
authors: Kai-Ren
authors: KR
authors: Ong
authors: Jackie
authors: J
authors: Cook
authors: Fiona
authors: F
authors: Douglas
authors: Shirley
authors: S
authors: Hodgson
authors: D Gareth
authors: DG
authors: Evans
authors: Rosalind
authors: R
authors: Eeles
authors: Bert
authors: B
authors: Gold
authors: Paul D P
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authors: Pharoah
authors: Kenneth
authors: K
authors: Offit
authors: Georgia
authors: G
authors: Chenevix-Trench
authors: Douglas F
authors: DF
authors: Easton
mesh_terms: D000483:Alleles; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics*; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D016001:Confidence Intervals; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D016016:Proportional Hazards Models; D011960:Receptors, Estrogen / Q000235:genetics; D012307:Risk Factors
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D011960:Receptors, Estrogen