title: Association of THADA, FOXP4, GPRC6A/RFX6 genes and 8q24 risk alleles with prostate cancer in Northern Chinese men.
abstract: OBJECTIVE
  Prostate cancer (PCa) is one of the most common malignancies in males, and multiple genetic studies have confirmed association with susceptibility to PCa. However, the risk conferred in men living in China is unkown. We selected 6 previously identified variants as candidates to define their association with PCa in Chinese men.
  
  
  METHODS
  We genotyped 6 single nucleotide polymorphisms (SNPs) (rs1465618, rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) using high resolution melting (HRM) analysis and assessed their association with PCa risk in a case-control study of 481 patients and 480 controls in a Chinese population. In addition, the individual and cumulative contribution for the risk of PCa and clinical covariates were analysed.
  
  
  RESULTS
  We found that 5 of the 6 genetic variants were associated with PCa risk. The T allele of rs339331 and the G allele of rs16901966 showed a significant association with PCa susceptibility: OR (95%CI)= 0.78 (0.64-0.94), p<0.009 and OR (95%CI)= 0.66 (0.54-0.81), p<0.0001, as well as A allele of rs1447295 (OR [95%CI]=1.46 (1.17-1.84), p<0.001) and T allele of rs10090154 (OR [95%CI]= 0.58 (0.46-0.74), p<0.0001). rs339331(T) was associated with a 0.71-fold and 1.42-fold increase of PCa risk by dominant model (p=0.007) and recessive model (p=0.007). rs16901966 (G) was associated with a 0.51-fold and 1.98-fold increase of PCa risk by dominant model (p=0.006) and recessive model (p=0.0058). rs10090154 (T) was associated with a 1.89-fold and 0.53-fold increase of PCa risk by dominant model (p=0.000006) and recessive model (p=0.000006). And, rs1983891(C) was associated with a 0.77-fold increase of PCa risk by recessive model (p=0.045). rs1447295 was associated with a 1.57-fold increase of PCa risk by dominant model (p=0.008). rs1465618 showed no significant association with PCa. The cumulative effects test of risk alleles (rs rs1983891, rs339331, rs16901966, rs1447295 and rs10090154) showed an increasing risk to PCa in a frequency-dependent manner (ptrend=0.001), and men with more than 3 risk alleles had the most significant susceptibility to PCa (OR=1.99, p=0.001), compared with those who had one risk allele (OR=1.17, p=0.486).
  
  
  CONCLUSIONS
  Our results provide further support for association of the THADA, FOXP4, GPRC6A/RFX6 and 8q24 genes with Pca in Asian populations. Further work is still required to determine the functional variations and finally clarify the underlying biological mechanisms.
authors.affiliation: School of Public Health, Ningxia Medical University, Yinchuan, China.
authors.forename: Xing-Hui
authors.initials: XH
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Kuo
authors.initials: K
authors.lastname: Yang
authors.forename: Jian-Jian
authors.initials: JJ
authors.lastname: Shi
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Huiping
authors.initials: H
authors.lastname: Yuan
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Zhu
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Zhang
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Wang
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002898:Chromosomes, Human, Pair 8; D004268:DNA-Binding Proteins / Q000235:genetics*; D051858:Forkhead Transcription Factors / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D000071701:Regulatory Factor X Transcription Factors; D012306:Risk; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D004268:DNA-Binding Proteins; C576732:FOXP4 protein, human; D051858:Forkhead Transcription Factors; C488584:GPRC6A protein, human; D009363:Neoplasm Proteins; D043562:Receptors, G-Protein-Coupled; D000071701:Regulatory Factor X Transcription Factors; C547964:Rfx6 protein, human; C477698:THADA protein, human; D014157:Transcription Factors