Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer.
Familial clustering studies indicate that breast cancer risk has a substantial genetic component. To identify new breast cancer risk variants, we genotyped approximately 300,000 SNPs in 1,600 Icelandic individuals with breast cancer and 11,563 controls using the Illumina Hap300 platform. We then tested selected SNPs in five replication sample sets. Overall, we studied 4,554 affected individuals and 17,577 controls. Two SNPs consistently associated with breast cancer: approximately 25% of individuals of European descent are homozygous for allele A of rs13387042 on chromosome 2q35 and have an estimated 1.44-fold greater risk than noncarriers, and for allele T of rs3803662 on 16q12, about 7% are homozygous and have a 1.64-fold greater risk. Risk from both alleles was confined to estrogen receptor-positive tumors. At present, no genes have been identified in the linkage disequilibrium block containing rs13387042. rs3803662 is near the 5' end of TNRC9 , a high mobility group chromatin-associated protein whose expression is implicated in breast cancer metastasis to bone.
Stacey
Simon N
SN
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. simon.stacey@decode.is
Manolescu
Andrei
A
Sulem
Patrick
P
Rafnar
Thorunn
T
Gudmundsson
Julius
J
Gudjonsson
Sigurjon A
SA
Masson
Gisli
G
Jakobsdottir
Margret
M
Thorlacius
Steinunn
S
Helgason
Agnar
A
Aben
Katja K
KK
Strobbe
Luc J
LJ
Albers-Akkers
Marjo T
MT
Swinkels
Dorine W
DW
Henderson
Brian E
BE
Kolonel
Laurence N
LN
Le Marchand
Loic
L
Millastre
Esther
E
Andres
Raquel
R
Godino
Javier
J
Garcia-Prats
Maria Dolores
MD
Polo
Eduardo
E
Tres
Alejandro
A
Mouy
Magali
M
Saemundsdottir
Jona
J
Backman
Valgerdur M
VM
Gudmundsson
Larus
L
Kristjansson
Kristleifur
K
Bergthorsson
Jon T
JT
Kostic
Jelena
J
Frigge
Michael L
ML
Geller
Frank
F
Gudbjartsson
Daniel
D
Sigurdsson
Helgi
H
Jonsdottir
Thora
T
Hrafnkelsson
Jon
J
Johannsson
Jakob
J
Sveinsson
Thorarinn
T
Myrdal
Gardar
G
Grimsson
Hlynur Niels
HN
Jonsson
Thorvaldur
T
von Holst
Susanna
S
Werelius
Barbro
B
Margolin
Sara
S
Lindblom
Annika
A
Mayordomo
Jose I
JI
Haiman
Christopher A
CA
Kiemeney
Lambertus A
LA
Johannsson
Oskar Th
OT
Gulcher
Jeffrey R
JR
Thorsteinsdottir
Unnur
U
Kong
Augustine
A
Stefansson
Kari
K
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D011960:Receptors, Estrogen / Q000096:biosynthesis*
D011960:Receptors, Estrogen