Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium.
The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (alpha) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (alpha = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at alpha = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.
Thompson
Deborah
D
CRC Genetic Epidemiology Unit, Strangeways Research Laboratories, University of Cambridge, Cambridge CB1 4RN, United Kingdom.
Szabo
Csilla I
CI
Mangion
Jon
J
Oldenburg
Rogier A
RA
Odefrey
Fabrice
F
Seal
Sheila
S
Barfoot
Rita
R
Kroeze-Jansema
Karin
K
Teare
Dawn
D
Rahman
Nazneen
N
Renard
Hélène
H
Mann
Graham
G
Hopper
John L
JL
Buys
Saundra S
SS
Andrulis
Irene L
IL
Senie
Ruby
R
Daly
Mary B
MB
West
Dee
D
Ostrander
Elaine A
EA
Offit
Ken
K
Peretz
Tamar
T
Osorio
Ana
A
Benitez
J
J
Nathanson
Katherine L
KL
Sinilnikova
Olga M
OM
Olàh
Edith
E
Bignon
Yves-Jean
YJ
Ruiz
Pablo
P
Badzioch
Michael D
MD
Vasen
Hans F A
HF
Futreal
Andrew P
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Phelan
Catherine M
CM
Narod
Steven A
SA
Lynch
Henry T
HT
Ponder
Bruce A J
BA
Eeles
Ros A
RA
Meijers-Heijboer
Hanne
H
Stoppa-Lyonnet
Dominique
D
Couch
Fergus J
FJ
Eccles
Diana M
DM
Evans
D Gareth
DG
Chang-Claude
Jenny
J
Lenoir
Gilbert
G
Weber
Barbara L
BL
Devilee
Peter
P
Easton
Douglas F
DF
Goldgar
David E
DE
Stratton
Michael R
MR
D001315:Australia; D001943:Breast Neoplasms / Q000235:genetics*; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D005060:Europe; D005260:Female; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D006801:Humans; D008126:Lod Score; D009656:North America