Replication and fine mapping for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in the Chinese population.
BACKGROUND
Prostate cancer represents the leading cause of male death across the world. A recent genome-wide association study (GWAS) identified five novel susceptibility loci for prostate cancer in the Japanese population. This study is to replicate and fine map the potential association of these five loci with prostate cancer in the Chinese Han population.


METHODS
In Phase I of the study, we tested the five single nucleotide polymorphisms (SNPs) which showed the strongest association evidence in the original GWAS in Japanese. The study sample consists of 1,169 Chinese Hans, comprising 483 patients and 686 healthy controls. Then in phase II, flanking SNPs of the successfully replicated SNPs in Phase I were genotyped and tested for association with prostate cancer to fine map those significant association signals.


RESULTS
We successfully replicated the association of rs13385191 (located in the C2orf43 gene, P = 8.60×10(-5)), rs12653946 (P = 1.33×10(-6)), rs1983891 (FOXP4, P = 6.22×10(-5)), and rs339331 (GPRC6A/RFX6, P = 1.42×10(-5)) with prostate cancer. The most significant odds ratio (OR) was recorded as 1.41 (95% confidence interval 1.18-1.68) for rs12653946. Rs9600079 did not show significant association (P = 8.07×10(-2)) with prostate cancer in this study. The Phase II study refined these association signals, and identified several SNPs showing more significant association with prostate cancer than the very SNPs tested in Phase I.


CONCLUSIONS
Our results provide further support for association of the C2orf43, FOXP4, GPRC6A and RFX6 genes with prostate cancer in Eastern Asian populations. This study also characterized the novel loci reported in the original GWAS with more details. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.
Department of Urology, the First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an Shaanxi, People's Republic of China. qingzhilong@yahoo.cn
Qing-Zhi
QZ
Long
Yue-Feng
YF
Du
Xiao-Ying
XY
Ding
Xiang
X
Li
Wen-Bin
WB
Song
Yong
Y
Yang
Peng
P
Zhang
Jian-Ping
JP
Zhou
Xiao-Gang
XG
Liu
D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D002874:Chromosome Mapping; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C576732:FOXP4 protein, human; D051858:Forkhead Transcription Factors; C488584:GPRC6A protein, human; C576733:LDAH protein, human; D009363:Neoplasm Proteins; D011506:Proteins; D043562:Receptors, G-Protein-Coupled; D000071701:Regulatory Factor X Transcription Factors; C547964:Rfx6 protein, human; D014157:Transcription Factors