Pooled Sample-Based GWAS: A Cost-Effective Alternative for Identifying Colorectal and Prostate Cancer Risk Variants in the Polish Population

被引：33

作者：

Gaj, Pawel ^{[1
]}

Maryan, Natalia ^{[1
]}

Hennig, Ewa E. ^{[1
,2
,3
]}

Ledwon, Joanna K. ^{[1
]}

Paziewska, Agnieszka ^{[1
]}

Majewska, Aneta ^{[1
]}

Karczmarski, Jakub ^{[2
,3
]}

Nesteruk, Monika ^{[1
]}

Wolski, Jan ^{[3
,4
]}

Antoniewicz, Artur A. ^{[5
]}

Przytulski, Krzysztof ^{[1
,2
,3
]}

Rutkowski, Andrzej ^{[3
,6
]}

Teumer, Alexander ^{[7
]}

Homuth, Georg ^{[7
]}

Starzynska, Teresa ^{[8
]}

Regula, Jaroslaw ^{[1
,2
,3
]}

Ostrowski, Jerzy ^{[1
,2
,3
]}

机构：

[1] Med Ctr Postgrad Educ, Dept Gastroenterol & Hepatol, Warsaw, Poland

[2] Maria Sklodowska Curie Mem Canc Ctr, Dept Oncol Genet, Warsaw, Poland

[3] Inst Oncol, Warsaw, Poland

[4] Maria Sklodowska Curie Mem Canc Ctr, Dept Urol, Warsaw, Poland

[5] Med Ctr Postgrad Educ, Dept Urol, Warsaw, Poland

[6] Maria Sklodowska Curie Mem Canc Ctr, Dept Colorectal Canc, Warsaw, Poland

[7] Ernst Moritz Arndt Univ Greifswald, Interfac Inst Genet & Funct Genom, Greifswald, Germany

[8] Pomeranian Med Univ, Dept Gastroenterol, Szczecin, Poland

来源：

PLOS ONE | 2012年 / 7卷 / 04期

关键词：

GENOME-WIDE ASSOCIATION; COMMON GENETIC-VARIANTS; SUSCEPTIBILITY LOCI; CHROMOSOME; 8Q24; MULTIPLE LOCI; HIDDEN HERITABILITY; EARLY-ONSET; IDENTIFICATION; SNPS; MEN;

D O I：

10.1371/journal.pone.0035307

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 chi(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.

引用

页数：12

共 90 条

[1]

Affymetrix Inc., 2005, AFF GENECHIP GEN AN

[2] Multiple loci on 8q24 associated with prostate cancer susceptibility [J].

Al Olama, Ali Amin ;

Kote-Jarai, Zsofia ;

Giles, Graham G. ;

Guy, Michelle ;

Morrison, Jonathan ;

Severi, Gianluca ;

Leongamornlert, Daniel A. ;

Tymrakiewicz, Malgorzata ;

Jhavar, Sameer ;

Saunders, Ed ;

Hopper, John L. ;

Southey, Melissa C. ;

Muir, Kenneth R. ;

English, Dallas R. ;

Dearnaley, David P. ;

Ardern-Jones, Audrey T. ;

Hall, Amanda L. ;

O'Brien, Lynne T. ;

Wilkinson, Rosemary A. ;

Sawyer, Emma ;

Lophatananon, Artitaya ;

Horwich, Alan ;

Huddart, Robert A. ;

Khoo, Vincent S. ;

Parker, Christopher C. ;

Woodhouse, Christopher J. ;

Thompson, Alan ;

Christmas, Tim ;

Ogden, Chris ;

Cooper, Colin ;

Donovan, Jenny L. ;

Hamdy, Freddie C. ;

Neal, David E. ;

Eeles, Rosalind A. ;

Easton, Douglas F. .

NATURE GENETICS, 2009, 41 (10) :1058-1060

[3]

Barratt BJ, 2002, ANN HUM GENET, V66, P393, DOI [10.1046/j.1469-1809.2002.00125.x, 10.1017/S0003480002001252]

[4] Evaluating coverage of genome-wide association studies [J].

Barrett, Jeffrey C. ;

Cardon, Lon R. .

NATURE GENETICS, 2006, 38 (06) :659-662

[5] Genomic and geographic distribution of private SNPs and pathways in human populations [J].

Baye, Tesfaye M. ;

Wilke, Russell A. ;

Olivier, Michael .

PERSONALIZED MEDICINE, 2009, 6 (06) :623-641

[6] Chromosome 8q24 markers: Risk of early-onset and familial prostate cancer [J].

Beebe-Dimmer, Jennifer L. ;

Levin, Albert M. ;

Ray, Anna M. ;

Zuhlke, Kimberly A. ;

Machiela, Mitchell J. ;

Halstead-Nussloch, Bronwen A. ;

Johnson, Gregory R. ;

Cooney, Kathleen A. ;

Douglas, Julie A. .

INTERNATIONAL JOURNAL OF CANCER, 2008, 122 (12) :2876-2879

[7] A genome-wide association study shows that common alleles of SMAD7 influence colorectal cancer risk [J].

Broderick, Peter ;

Carvajal-Carmona, Luis ;

Pittman, Alan M. ;

Webb, Emily ;

Howarth, Kimberley ;

Rowan, Andrew ;

Lubbe, Steven ;

Spain, Sarah ;

Sullivan, Kate ;

Fielding, Sarah ;

Jaeger, Emma ;

Vijayakrishnan, Jayaram ;

Kemp, Zoe ;

Gorman, Maggie ;

Chandler, Ian ;

Papaemmanuil, Elli ;

Penegar, Steven ;

Wood, Wendy ;

Sellick, Gabrielle ;

Qureshi, Mobshra ;

Teixeira, Ana ;

Domingo, Enric ;

Barclay, Ella ;

Martin, Lynn ;

Sieber, Oliver ;

Kerr, David ;

Gray, Richard ;

Peto, Julian ;

Cazier, Jean-Baptiste ;

Tomlinson, Ian ;

Houlston, Richard S. .

NATURE GENETICS, 2007, 39 (11) :1315-1317

[8] Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains [J].

Cal, S ;

Obaya, AJ ;

Llamazares, M ;

Garabaya, C ;

Quesada, V ;

López-Otín, C .

GENE, 2002, 283 (1-2) :49-62

[9] Validation of Genome-Wide Prostate Cancer Associations in Men of African Descent [J].

Chang, Bao-Li ;

Spangler, Elaine ;

Gallagher, Stephen ;

Haiman, Christopher A. ;

Henderson, Brian ;

Isaacs, William ;

Benford, Marnita L. ;

Kidd, LaCreis R. ;

Cooney, Kathleen ;

Strom, Sara ;

Ingles, Sue Ann ;

Stern, Mariana C. ;

Corral, Roman ;

Joshi, Amit D. ;

Xu, Jianfeng ;

Giri, Veda N. ;

Rybicki, Benjamin ;

Neslund-Dudas, Christine ;

Kibel, Adam S. ;

Thompson, Ian M. ;

Leach, Robin J. ;

Ostrander, Elaine A. ;

Stanford, Janet L. ;

Witte, John ;

Casey, Graham ;

Eeles, Rosalind ;

Hsing, Ann W. ;

Chanock, Stephen ;

Hu, Jennifer J. ;

John, Esther M. ;

Park, Jong ;

Stefflova, Klara ;

Zeigler-Johnson, Charnita ;

Rebbeck, Timothy R. .

CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2011, 20 (01) :23-32

[10] Identification of disease causing loci using an array-based genotyping approach on pooled DNA [J].

Craig, DW ;

Huentelman, MJ ;

Hu-Lince, D ;

Zismann, VL ;

Kruer, MC ;

Lee, AM ;

Puffenberger, EG ;

Pearson, JM ;

Stephan, DA .

BMC GENOMICS, 2005, 6 (1)

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