AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a consortium of investigators of modifiers of BRCA1/2 study.
The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 31I allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.06]. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% CI, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
Couch
Fergus J
FJ
Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, 200 First Street Southwest, Rochester, MN 55905, USA. Couch.fergus@mayo.edu
Sinilnikova
Olga
O
Vierkant
Robert A
RA
Pankratz
V Shane
VS
Fredericksen
Zachary S
ZS
Stoppa-Lyonnet
Dominique
D
Coupier
Isabelle
I
Hughes
David
D
Hardouin
Agnès
A
Berthet
Pascaline
P
Peock
Susan
S
Cook
Margaret
M
Baynes
Caroline
C
Hodgson
Shirley
S
Morrison
Patrick J
PJ
Porteous
Mary E
ME
Jakubowska
Anna
A
Lubinski
Jan
J
Gronwald
Jacek
J
Spurdle
Amanda B
AB
Schmutzler
Rita
R
Versmold
Beatrix
B
Engel
Christoph
C
Meindl
Alfons
A
Sutter
Christian
C
Horst
Jurgen
J
Schaefer
Dieter
D
Offit
Kenneth
K
Kirchhoff
Tomas
T
Andrulis
Irene L
IL
Ilyushik
Eduard
E
Glendon
Gordon
G
Devilee
Peter
P
Vreeswijk
Maaike P G
MP
Vasen
Hans F A
HF
Borg
Ake
A
Backenhorn
Katja
K
Struewing
Jeffery P
JP
Greene
Mark H
MH
Neuhausen
Susan L
SL
Rebbeck
Timothy R
TR
Nathanson
Katherine
K
Domchek
Susan
S
Wagner
Theresa
T
Garber
Judy E
JE
Szabo
Csilla
C
Zikan
Michal
M
Foretova
Lenka
L
Olson
Janet E
JE
Sellers
Thomas A
TA
Lindor
Noralane
N
Nevanlinna
Heli
H
Tommiska
Johanna
J
Aittomaki
Kristiina
K
Hamann
Ute
U
Rashid
Muhammad U
MU
Torres
Diana
D
Simard
Jacques
J
Durocher
Francine
F
Guenard
Frederic
F
Lynch
Henry T
HT
Isaacs
Claudine
C
Weitzel
Jeffrey
J
Olopade
Olufunmilayo I
OI
Narod
Steven
S
Daly
Mary B
MB
Godwin
Andrew K
AK
Tomlinson
Gail
G
Easton
Douglas F
DF
Chenevix-Trench
Georgia
G
Antoniou
Antonis C
AC
D000328:Adult; D017668:Age of Onset; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D015996:Survival Rate
C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases