Systematic replication study of reported genetic associations in prostate cancer: Strong support for genetic variation in the androgen pathway.
BACKGROUND
Association studies have become a common and popular method to identify genetic variants predisposing to complex diseases. Despite considerable efforts and initial promising findings, the field of prostate cancer genetics is characterized by inconclusive reports and no prostate cancer gene has yet been established.


METHODS
We performed a literature review and identified 79 different polymorphisms reported to influence prostate cancer risk. Of these, 46 were selected and tested for association in a large Swedish population-based case-control prostate cancer population.


RESULTS
We observed significant (P < 0.05) confirmation for six polymorphisms located in five different genes. Three of them coded for key enzymes in the androgen biosynthesis and response pathway; the CAG repeat in the androgen receptor (AR) gene (P = 0.03), one SNP in the CYP17 gene (P = 0.04), two SNPs in the SRD5A2 gene (P = 0.02 and 0.02, respectively), a deletion of the GSTT1 gene (P = 0.006), and one SNP in the MSR1 gene, IVS5-59C > A, (P = 0.009).


CONCLUSIONS
Notwithstanding the difficulties to replicate findings in genetic association studies, our results strongly support the importance of androgen pathway genes in prostate cancer etiology.
Lindström
Sara
S
Department of Radiation Sciences, Oncology, University of Umeå, Umeå, Sweden.
Zheng
S Lilly
SL
Wiklund
Fredrik
F
Jonsson
Björn-Anders
BA
Adami
Hans-Olov
HO
Bälter
Katarina Augustsson
KA
Brookes
Anthony J
AJ
Sun
Jielin
J
Chang
Bao-Li
BL
Liu
Wennuan
W
Li
Ge
G
Isaacs
William B
WB
Adolfsson
Jan
J
Grönberg
Henrik
H
Xu
Jianfeng
J
D000368:Aged; D000728:Androgens / Q000096:biosynthesis*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid
D000728:Androgens