Genome-wide association study identifies a second prostate cancer susceptibility variant at 8q24.
Prostate cancer is the most prevalent noncutaneous cancer in males in developed regions, with African American men having among the highest worldwide incidence and mortality rates. Here we report a second genetic variant in the 8q24 region that, in conjunction with another variant we recently discovered, accounts for about 11%-13% of prostate cancer cases in individuals of European descent and 31% of cases in African Americans. We made the current discovery through a genome-wide association scan of 1,453 affected Icelandic individuals and 3,064 controls using the Illumina HumanHap300 BeadChip followed by four replication studies. A key step in the discovery was the construction of a 14-SNP haplotype that efficiently tags a relatively uncommon (2%-4%) susceptibility variant in individuals of European descent that happens to be very common (approximately 42%) in African Americans. The newly identified variant shows a stronger association with affected individuals who have an earlier age at diagnosis.
Gudmundsson
Julius
J
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
Sulem
Patrick
P
Manolescu
Andrei
A
Amundadottir
Laufey T
LT
Gudbjartsson
Daniel
D
Helgason
Agnar
A
Rafnar
Thorunn
T
Bergthorsson
Jon T
JT
Agnarsson
Bjarni A
BA
Baker
Adam
A
Sigurdsson
Asgeir
A
Benediktsdottir
Kristrun R
KR
Jakobsdottir
Margret
M
Xu
Jianfeng
J
Blondal
Thorarinn
T
Kostic
Jelena
J
Sun
Jielin
J
Ghosh
Shyamali
S
Stacey
Simon N
SN
Mouy
Magali
M
Saemundsdottir
Jona
J
Backman
Valgerdur M
VM
Kristjansson
Kristleifur
K
Tres
Alejandro
A
Partin
Alan W
AW
Albers-Akkers
Marjo T
MT
Godino-Ivan Marcos
Javier
J
Walsh
Patrick C
PC
Swinkels
Dorine W
DW
Navarrete
Sebastian
S
Isaacs
Sarah D
SD
Aben
Katja K
KK
Graif
Theresa
T
Cashy
John
J
Ruiz-Echarri
Manuel
M
Wiley
Kathleen E
KE
Suarez
Brian K
BK
Witjes
J Alfred
JA
Frigge
Mike
M
Ober
Carole
C
Jonsson
Eirikur
E
Einarsson
Gudmundur V
GV
Mayordomo
Jose I
JI
Kiemeney
Lambertus A
LA
Isaacs
William B
WB
Catalona
William J
WJ
Barkardottir
Rosa B
RB
Gulcher
Jeffrey R
JR
Thorsteinsdottir
Unnur
U
Kong
Augustine
A
Stefansson
Kari
K
D001741:Black or African American; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D005060:Europe; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation; D023281:Genomics / Q000379:methods; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics*; D014481:United States; D044465:White People