title: Pooled sample-based GWAS: a cost-effective alternative for identifying colorectal and prostate cancer risk variants in the Polish population.
abstract: BACKGROUND
  Prostate cancer (PCa) and colorectal cancer (CRC) are the most commonly diagnosed cancers and cancer-related causes of death in Poland. To date, numerous single nucleotide polymorphisms (SNPs) associated with susceptibility to both cancer types have been identified, but their effect on disease risk may differ among populations.
  
  
  METHODS
  To identify new SNPs associated with PCa and CRC in the Polish population, a genome-wide association study (GWAS) was performed using DNA sample pools on Affymetrix Genome-Wide Human SNP 6.0 arrays. A total of 135 PCa patients and 270 healthy men (PCa sub-study) and 525 patients with adenoma (AD), 630 patients with CRC and 690 controls (AD/CRC sub-study) were included in the analysis. Allele frequency distributions were compared with t-tests and χ(2)-tests. Only those significantly associated SNPs with a proxy SNP (p<0.001; distance of 100 kb; r(2)>0.7) were selected. GWAS marker selection was conducted using PLINK. The study was replicated using extended cohorts of patients and controls. The association with previously reported PCa and CRC susceptibility variants was also examined. Individual patients were genotyped using TaqMan SNP Genotyping Assays.
  
  
  RESULTS
  The GWAS selected six and 24 new candidate SNPs associated with PCa and CRC susceptibility, respectively. In the replication study, 17 of these associations were confirmed as significant in additive model of inheritance. Seven of them remained significant after correction for multiple hypothesis testing. Additionally, 17 previously reported risk variants have been identified, five of which remained significant after correction.
  
  
  CONCLUSIONS
  Pooled-DNA GWAS enabled the identification of new susceptibility loci for CRC in the Polish population. Previously reported CRC and PCa predisposition variants were also identified, validating the global nature of their associations. Further independent replication studies are required to confirm significance of the newly uncovered candidate susceptibility loci.
authors.affiliation: Department of Gastroenterology and Hepatology, Medical Center for Postgraduate Education, Warsaw, Poland.
authors.forename: Pawel
authors.initials: P
authors.lastname: Gaj
authors.forename: Natalia
authors.initials: N
authors.lastname: Maryan
authors.forename: Ewa E
authors.initials: EE
authors.lastname: Hennig
authors.forename: Joanna K
authors.initials: JK
authors.lastname: Ledwon
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Paziewska
authors.forename: Aneta
authors.initials: A
authors.lastname: Majewska
authors.forename: Jakub
authors.initials: J
authors.lastname: Karczmarski
authors.forename: Monika
authors.initials: M
authors.lastname: Nesteruk
authors.forename: Jan
authors.initials: J
authors.lastname: Wolski
authors.forename: Artur A
authors.initials: AA
authors.lastname: Antoniewicz
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Przytulski
authors.forename: Andrzej
authors.initials: A
authors.lastname: Rutkowski
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.forename: Georg
authors.initials: G
authors.lastname: Homuth
authors.forename: Teresa
authors.initials: T
authors.lastname: Starzyńska
authors.forename: Jaroslaw
authors.initials: J
authors.lastname: Regula
authors.forename: Jerzy
authors.initials: J
authors.lastname: Ostrowski
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000191:economics / Q000235:genetics*; D003362:Cost-Benefit Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000191:economics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000191:economics / Q000235:genetics*; D012307:Risk Factors; D044465:White People / Q000235:genetics