TY - JOUR
T1 - Pooled sample-based gwas
T2 - A cost-effective alternative for identifying colorectal and prostate cancer risk variants in the polish population
AU - Gaj, Pawel
AU - Maryan, Natalia
AU - Hennig, Ewa E.
AU - Ledwon, Joanna Karolina
AU - Paziewska, Agnieszka
AU - Majewska, Aneta
AU - Karczmarski, Jakub
AU - Nesteruk, Monika
AU - Wolski, Jan
AU - Antoniewicz, Artur A.
AU - Przytulski, Krzysztof
AU - Rutkowski, Andrzej
AU - Teumer, Alexander
AU - Homuth, Georg
AU - Starzyńska, Teresa
AU - Regula, Jaroslaw
AU - Ostrowski, Jerzy
PY - 2012/4/19
Y1 - 2012/4/19
N2 - 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. Conclusion: 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.
AB - 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. Conclusion: 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.
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U2 - 10.1371/journal.pone.0035307
DO - 10.1371/journal.pone.0035307
M3 - Article
C2 - 22532847
AN - SCOPUS:84859841512
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 4
M1 - e35307
ER -