Multiple novel prostate cancer predisposition loci confirmed by an international study: the PRACTICAL Consortium.
A recent genome-wide association study found that genetic variants on chromosomes 3, 6, 7, 10, 11, 19 and X were associated with prostate cancer risk. We evaluated the most significant single-nucleotide polymorphisms (SNP) in these loci using a worldwide consortium of 13 groups (PRACTICAL). Blood DNA from 7,370 prostate cancer cases and 5,742 male controls was analyzed by genotyping assays. Odds ratios (OR) associated with each genotype were estimated using unconditional logistic regression. Six of the seven SNPs showed clear evidence of association with prostate cancer (P = 0.0007-P = 10(-17)). For each of these six SNPs, the estimated per-allele OR was similar to those previously reported and ranged from 1.12 to 1.29. One SNP on 3p12 (rs2660753) showed a weaker association than previously reported [per-allele OR, 1.08 (95% confidence interval, 1.00-1.16; P = 0.06) versus 1.18 (95% confidence interval, 1.06-1.31)]. The combined risks associated with each pair of SNPs were consistent with a multiplicative risk model. Under this model, and in combination with previously reported SNPs on 8q and 17q, these loci explain 16% of the familial risk of the disease, and men in the top 10% of the risk distribution have a 2.1-fold increased risk relative to general population rates. This study provides strong confirmation of these susceptibility loci in multiple populations and shows that they make an important contribution to prostate cancer risk prediction.
Kote-Jarai
Zsofia
Z
Section of Cancer Genetics Team, The Institute of Cancer Research, 15 Cotswold Road, Sutton, Surrey SM2 5NG, United Kingdom.
Easton
Douglas F
DF
Stanford
Janet L
JL
Ostrander
Elaine A
EA
Schleutker
Johanna
J
Ingles
Sue A
SA
Schaid
Daniel
D
Thibodeau
Stephen
S
Dörk
Thilo
T
Neal
David
D
Donovan
Jenny
J
Hamdy
Freddie
F
Cox
Angela
A
Maier
Christiane
C
Vogel
Walter
W
Guy
Michelle
M
Muir
Kenneth
K
Lophatananon
Artitaya
A
Kedda
Mary-Anne
MA
Spurdle
Amanda
A
Steginga
Suzanne
S
John
Esther M
EM
Giles
Graham
G
Hopper
John
J
Chappuis
Pierre O
PO
Hutter
Pierre
P
Foulkes
William D
WD
Hamel
Nancy
N
Salinas
Claudia A
CA
Koopmeiners
Joseph S
JS
Karyadi
Danielle M
DM
Johanneson
Bo
B
Wahlfors
Tiina
T
Tammela
Teuvo L
TL
Stern
Mariana C
MC
Corral
Roman
R
McDonnell
Shannon K
SK
Schürmann
Peter
P
Meyer
Andreas
A
Kuefer
Rainer
R
Leongamornlert
Daniel A
DA
Tymrakiewicz
Malgorzata
M
Liu
Jo-Fen
JF
O'Mara
Tracy
T
Gardiner
R A Frank
RA
Aitken
Joanne
J
Joshi
Amit D
AD
Severi
Gianluca
G
English
Dallas R
DR
Southey
Melissa
M
Edwards
Stephen M
SM
Al Olama
Ali Amin
AA
Eeles
Rosalind A
RA
D000483:Alleles; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012306:Risk