A common variant at 8q24.21 is associated with renal cell cancer.
Renal cell carcinoma (RCC) represents between 80 and 90% of kidney cancers. Previous genome-wide association studies of RCC have identified five variants conferring risk of the disease. Here we report the results from a discovery RCC genome-wide association study and replication analysis, including a total of 2,411 patients and 71,497 controls. One variant, rs35252396[CG] located at 8q24.21, is significantly associated with RCC after combining discovery and replication results (OR=1.27, P(combined)=5.4 × 10(-11)) and has an average risk allele frequency in controls of 46%. rs35252396[CG] does not have any strongly correlated variants in the genome and is located within a region predicted to have regulatory functions in several cell lines, including six originating from the kidney. This is the first RCC variant reported at 8q24.21 and it is largely independent (r(2)≤0.02) of the numerous previously reported cancer risk variants at this locus.
1] DeCODE genetics Inc./AMGEN, Sturlugata 8, IS-101 Reykjavik, Iceland [2].
Julius
J
Gudmundsson
Patrick
P
Sulem
Daniel F
DF
Gudbjartsson
Gisli
G
Masson
Vigdis
V
Petursdottir
Sverrir
S
Hardarson
Sigurjon A
SA
Gudjonsson
Hrefna
H
Johannsdottir
Hafdis Th
HT
Helgadottir
Simon N
SN
Stacey
Olafur Th
OT
Magnusson
Hannes
H
Helgason
Angeles
A
Panadero
Loes F
LF
van der Zanden
Katja K H
KK
Aben
Sita H
SH
Vermeulen
Egbert
E
Oosterwijk
Augustine
A
Kong
Jose I
JI
Mayordomo
Asgerdur
A
Sverrisdottir
Eirikur
E
Jonsson
Tomas
T
Gudbjartsson
Gudmundur V
GV
Einarsson
Lambertus A
LA
Kiemeney
Unnur
U
Thorsteinsdottir
Thorunn
T
Rafnar
Kari
K
Stefansson
D000368:Aged; D002292:Carcinoma, Renal Cell / Q000453:epidemiology / Q000235:genetics*; D019295:Computational Biology; D015972:Gene Expression Regulation, Neoplastic; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D007680:Kidney Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors