Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Filters applied. Clear all
Meta-Analysis
. 2014 Sep;46(9):994-1000.
doi: 10.1038/ng.3052. Epub 2014 Aug 3.

Genome-wide Association Study Identifies Multiple Susceptibility Loci for Pancreatic Cancer

Brian M Wolpin  1 Cosmeri Rizzato  2 Peter Kraft  3 Charles Kooperberg  4 Gloria M Petersen  5 Zhaoming Wang  6 Alan A Arslan  7 Laura Beane-Freeman  8 Paige M Bracci  9 Julie Buring  10 Federico Canzian  11 Eric J Duell  12 Steven Gallinger  13 Graham G Giles  14 Gary E Goodman  15 Phyllis J Goodman  16 Eric J Jacobs  17 Aruna Kamineni  18 Alison P Klein  19 Laurence N Kolonel  20 Matthew H Kulke  21 Donghui Li  22 Núria Malats  23 Sara H Olson  24 Harvey A Risch  25 Howard D Sesso  26 Kala Visvanathan  27 Emily White  28 Wei Zheng  29 Christian C Abnet  8 Demetrius Albanes  8 Gabriella Andreotti  8 Melissa A Austin  30 Richard Barfield  31 Daniela Basso  32 Sonja I Berndt  8 Marie-Christine Boutron-Ruault  33 Michelle Brotzman  34 Markus W Büchler  35 H Bas Bueno-de-Mesquita  36 Peter Bugert  37 Laurie Burdette  6 Daniele Campa  38 Neil E Caporaso  8 Gabriele Capurso  39 Charles Chung  6 Michelle Cotterchio  40 Eithne Costello  41 Joanne Elena  42 Niccola Funel  43 J Michael Gaziano  44 Nathalia A Giese  35 Edward L Giovannucci  45 Michael Goggins  46 Megan J Gorman  21 Myron Gross  47 Christopher A Haiman  48 Manal Hassan  22 Kathy J Helzlsouer  49 Brian E Henderson  50 Elizabeth A Holly  9 Nan Hu  8 David J Hunter  51 Federico Innocenti  52 Mazda Jenab  53 Rudolf Kaaks  38 Timothy J Key  54 Kay-Tee Khaw  55 Eric A Klein  56 Manolis Kogevinas  57 Vittorio Krogh  58 Juozas Kupcinskas  59 Robert C Kurtz  60 Andrea LaCroix  15 Maria T Landi  8 Stefano Landi  61 Loic Le Marchand  62 Andrea Mambrini  63 Satu Mannisto  64 Roger L Milne  65 Yusuke Nakamura  66 Ann L Oberg  67 Kouros Owzar  68 Alpa V Patel  17 Petra H M Peeters  69 Ulrike Peters  70 Raffaele Pezzilli  71 Ada Piepoli  72 Miquel Porta  73 Francisco X Real  74 Elio Riboli  75 Nathaniel Rothman  8 Aldo Scarpa  76 Xiao-Ou Shu  29 Debra T Silverman  8 Pavel Soucek  77 Malin Sund  78 Renata Talar-Wojnarowska  79 Philip R Taylor  8 George E Theodoropoulos  80 Mark Thornquist  15 Anne Tjønneland  81 Geoffrey S Tobias  8 Dimitrios Trichopoulos  82 Pavel Vodicka  83 Jean Wactawski-Wende  84 Nicolas Wentzensen  8 Chen Wu  85 Herbert Yu  62 Kai Yu  8 Anne Zeleniuch-Jacquotte  86 Robert Hoover  8 Patricia Hartge  87 Charles Fuchs  88 Stephen J Chanock  89 Rachael S Stolzenberg-Solomon  87 Laufey T Amundadottir  87
Affiliations
Free PMC article
Meta-Analysis

Genome-wide Association Study Identifies Multiple Susceptibility Loci for Pancreatic Cancer

Brian M Wolpin et al. Nat Genet. .
Free PMC article

Abstract

We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74-0.84, P = 3.0 × 10(-12)), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30-1.65, P = 1.1 × 10(-10)), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10-1.20, P = 2.4 × 10(-9)) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12-1.25, P = 1.2 × 10(-8)). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76-0.85, P = 9.8 × 10(-14)). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10(-7)) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

Figures

Figure 1
Figure 1. Association results, recombination hotspots and LD plots for new pancreatic cancer susceptibility regions (a–e) and one suggestive region (f)
Top, association results of GWAS data from the stage 1 (gray diamonds), stage 2 (purple diamonds), replication (blue diamonds) and the combined data from stages 1–3 (red diamonds) plotted against −log10 P values (left y axis). Overlaid are likelihood ratio statistics (right y axis) estimating putative recombination hotspots across the region on the basis of five unique sets of 100 randomly selected control samples. Bottom, LD heat map based on r2 values from the total control populations for all SNPs included in the GWAS. The data are based on a total number of 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Shown are results for 5p15.33 (a), 7q32.3 (b), 16q23.1 (c), 13q12.2 (d), 22q12.1 (e), and 8q24.1 (f).
Figure 1
Figure 1. Association results, recombination hotspots and LD plots for new pancreatic cancer susceptibility regions (a–e) and one suggestive region (f)
Top, association results of GWAS data from the stage 1 (gray diamonds), stage 2 (purple diamonds), replication (blue diamonds) and the combined data from stages 1–3 (red diamonds) plotted against −log10 P values (left y axis). Overlaid are likelihood ratio statistics (right y axis) estimating putative recombination hotspots across the region on the basis of five unique sets of 100 randomly selected control samples. Bottom, LD heat map based on r2 values from the total control populations for all SNPs included in the GWAS. The data are based on a total number of 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Shown are results for 5p15.33 (a), 7q32.3 (b), 16q23.1 (c), 13q12.2 (d), 22q12.1 (e), and 8q24.1 (f).
Figure 1
Figure 1. Association results, recombination hotspots and LD plots for new pancreatic cancer susceptibility regions (a–e) and one suggestive region (f)
Top, association results of GWAS data from the stage 1 (gray diamonds), stage 2 (purple diamonds), replication (blue diamonds) and the combined data from stages 1–3 (red diamonds) plotted against −log10 P values (left y axis). Overlaid are likelihood ratio statistics (right y axis) estimating putative recombination hotspots across the region on the basis of five unique sets of 100 randomly selected control samples. Bottom, LD heat map based on r2 values from the total control populations for all SNPs included in the GWAS. The data are based on a total number of 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Shown are results for 5p15.33 (a), 7q32.3 (b), 16q23.1 (c), 13q12.2 (d), 22q12.1 (e), and 8q24.1 (f).
Figure 1
Figure 1. Association results, recombination hotspots and LD plots for new pancreatic cancer susceptibility regions (a–e) and one suggestive region (f)
Top, association results of GWAS data from the stage 1 (gray diamonds), stage 2 (purple diamonds), replication (blue diamonds) and the combined data from stages 1–3 (red diamonds) plotted against −log10 P values (left y axis). Overlaid are likelihood ratio statistics (right y axis) estimating putative recombination hotspots across the region on the basis of five unique sets of 100 randomly selected control samples. Bottom, LD heat map based on r2 values from the total control populations for all SNPs included in the GWAS. The data are based on a total number of 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Shown are results for 5p15.33 (a), 7q32.3 (b), 16q23.1 (c), 13q12.2 (d), 22q12.1 (e), and 8q24.1 (f).
Figure 1
Figure 1. Association results, recombination hotspots and LD plots for new pancreatic cancer susceptibility regions (a–e) and one suggestive region (f)
Top, association results of GWAS data from the stage 1 (gray diamonds), stage 2 (purple diamonds), replication (blue diamonds) and the combined data from stages 1–3 (red diamonds) plotted against −log10 P values (left y axis). Overlaid are likelihood ratio statistics (right y axis) estimating putative recombination hotspots across the region on the basis of five unique sets of 100 randomly selected control samples. Bottom, LD heat map based on r2 values from the total control populations for all SNPs included in the GWAS. The data are based on a total number of 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Shown are results for 5p15.33 (a), 7q32.3 (b), 16q23.1 (c), 13q12.2 (d), 22q12.1 (e), and 8q24.1 (f).
Figure 1
Figure 1. Association results, recombination hotspots and LD plots for new pancreatic cancer susceptibility regions (a–e) and one suggestive region (f)
Top, association results of GWAS data from the stage 1 (gray diamonds), stage 2 (purple diamonds), replication (blue diamonds) and the combined data from stages 1–3 (red diamonds) plotted against −log10 P values (left y axis). Overlaid are likelihood ratio statistics (right y axis) estimating putative recombination hotspots across the region on the basis of five unique sets of 100 randomly selected control samples. Bottom, LD heat map based on r2 values from the total control populations for all SNPs included in the GWAS. The data are based on a total number of 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Shown are results for 5p15.33 (a), 7q32.3 (b), 16q23.1 (c), 13q12.2 (d), 22q12.1 (e), and 8q24.1 (f).

Similar articles

  • Common variation at 2p13.3, 3q29, 7p13 and 17q25.1 associated with susceptibility to pancreatic cancer.
    Childs EJ, Mocci E, Campa D, Bracci PM, Gallinger S, Goggins M, Li D, Neale RE, Olson SH, Scelo G, Amundadottir LT, Bamlet WR, Bijlsma MF, Blackford A, Borges M, Brennan P, Brenner H, Bueno-de-Mesquita HB, Canzian F, Capurso G, Cavestro GM, Chaffee KG, Chanock SJ, Cleary SP, Cotterchio M, Foretova L, Fuchs C, Funel N, Gazouli M, Hassan M, Herman JM, Holcatova I, Holly EA, Hoover RN, Hung RJ, Janout V, Key TJ, Kupcinskas J, Kurtz RC, Landi S, Lu L, Malecka-Panas E, Mambrini A, Mohelnikova-Duchonova B, Neoptolemos JP, Oberg AL, Orlow I, Pasquali C, Pezzilli R, Rizzato C, Saldia A, Scarpa A, Stolzenberg-Solomon RZ, Strobel O, Tavano F, Vashist YK, Vodicka P, Wolpin BM, Yu H, Petersen GM, Risch HA, Klein AP. Childs EJ, et al. Nat Genet. 2015 Aug;47(8):911-6. doi: 10.1038/ng.3341. Epub 2015 Jun 22. Nat Genet. 2015. PMID: 26098869 Free PMC article. Clinical Trial.
  • A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.
    Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, Jacobs KB, Arslan AA, Bueno-de-Mesquita HB, Gallinger S, Gross M, Helzlsouer K, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Li D, Mandelson MT, Olson SH, Risch HA, Zheng W, Albanes D, Bamlet WR, Berg CD, Boutron-Ruault MC, Buring JE, Bracci PM, Canzian F, Clipp S, Cotterchio M, de Andrade M, Duell EJ, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hassan M, Howard B, Hunter DJ, Hutchinson A, Jenab M, Kaaks R, Kooperberg C, Krogh V, Kurtz RC, Lynch SM, McWilliams RR, Mendelsohn JB, Michaud DS, Parikh H, Patel AV, Peeters PH, Rajkovic A, Riboli E, Rodriguez L, Seminara D, Shu XO, Thomas G, Tjønneland A, Tobias GS, Trichopoulos D, Van Den Eeden SK, Virtamo J, Wactawski-Wende J, Wang Z, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Fraumeni JF Jr, Hoover RN, Hartge P, Chanock SJ. Petersen GM, et al. Nat Genet. 2010 Mar;42(3):224-8. doi: 10.1038/ng.522. Epub 2010 Jan 24. Nat Genet. 2010. PMID: 20101243 Free PMC article.
  • Three new pancreatic cancer susceptibility signals identified on chromosomes 1q32.1, 5p15.33 and 8q24.21.
    Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, Figlioli G, Mocci E, Collins I, Chung CC, Hautman C, Arslan AA, Beane-Freeman L, Bracci PM, Buring J, Duell EJ, Gallinger S, Giles GG, Goodman GE, Goodman PJ, Kamineni A, Kolonel LN, Kulke MH, Malats N, Olson SH, Sesso HD, Visvanathan K, White E, Zheng W, Abnet CC, Albanes D, Andreotti G, Brais L, Bueno-de-Mesquita HB, Basso D, Berndt SI, Boutron-Ruault MC, Bijlsma MF, Brenner H, Burdette L, Campa D, Caporaso NE, Capurso G, Cavestro GM, Cotterchio M, Costello E, Elena J, Boggi U, Gaziano JM, Gazouli M, Giovannucci EL, Goggins M, Gross M, Haiman CA, Hassan M, Helzlsouer KJ, Hu N, Hunter DJ, Iskierka-Jazdzewska E, Jenab M, Kaaks R, Key TJ, Khaw KT, Klein EA, Kogevinas M, Krogh V, Kupcinskas J, Kurtz RC, Landi MT, Landi S, Le Marchand L, Mambrini A, Mannisto S, Milne RL, Neale RE, Oberg AL, Panico S, Patel AV, Peeters PH, Peters U, Pezzilli R, Porta M, Purdue M, Quiros JR, Riboli E, Rothman N, Scarpa A, Scelo G, Shu XO, Silverman DT, Soucek P, Strobel O, Sund M, Małecka-Panas E, Taylor PR, Tavano F, Travis RC, Thornquist M, Tjønneland A, Tobias GS, Trichopoulos D, Vashist Y, Vodicka P, Wactawski-Wende J, Wentzensen N, Yu H, Yu K, Zeleniuch-Jacquotte A, Kooperberg C, Risch HA, Jacobs EJ, Li D, Fuchs C, Hoover R, Hartge P, Chanock SJ, Petersen GM, Stolzenberg-Solomon RS, Wolpin BM, Kraft P, Klein AP, Canzian F, Amundadottir LT. Zhang M, et al. Oncotarget. 2016 Oct 11;7(41):66328-66343. doi: 10.18632/oncotarget.11041. Oncotarget. 2016. PMID: 27579533 Free PMC article.
  • A genome-wide association study identifies two new lung cancer susceptibility loci at 13q12.12 and 22q12.2 in Han Chinese.
    Hu Z, Wu C, Shi Y, Guo H, Zhao X, Yin Z, Yang L, Dai J, Hu L, Tan W, Li Z, Deng Q, Wang J, Wu W, Jin G, Jiang Y, Yu D, Zhou G, Chen H, Guan P, Chen Y, Shu Y, Xu L, Liu X, Liu L, Xu P, Han B, Bai C, Zhao Y, Zhang H, Yan Y, Ma H, Chen J, Chu M, Lu F, Zhang Z, Chen F, Wang X, Jin L, Lu J, Zhou B, Lu D, Wu T, Lin D, Shen H. Hu Z, et al. Nat Genet. 2011 Jul 3;43(8):792-6. doi: 10.1038/ng.875. Nat Genet. 2011. PMID: 21725308
  • Identification of Genetic Susceptibility Loci for Colorectal Tumors in a Genome-Wide Meta-analysis.
    Peters U, Jiao S, Schumacher FR, Hutter CM, Aragaki AK, Baron JA, Berndt SI, Bézieau S, Brenner H, Butterbach K, Caan BJ, Campbell PT, Carlson CS, Casey G, Chan AT, Chang-Claude J, Chanock SJ, Chen LS, Coetzee GA, Coetzee SG, Conti DV, Curtis KR, Duggan D, Edwards T, Fuchs CS, Gallinger S, Giovannucci EL, Gogarten SM, Gruber SB, Haile RW, Harrison TA, Hayes RB, Henderson BE, Hoffmeister M, Hopper JL, Hudson TJ, Hunter DJ, Jackson RD, Jee SH, Jenkins MA, Jia WH, Kolonel LN, Kooperberg C, Küry S, Lacroix AZ, Laurie CC, Laurie CA, Le Marchand L, Lemire M, Levine D, Lindor NM, Liu Y, Ma J, Makar KW, Matsuo K, Newcomb PA, Potter JD, Prentice RL, Qu C, Rohan T, Rosse SA, Schoen RE, Seminara D, Shrubsole M, Shu XO, Slattery ML, Taverna D, Thibodeau SN, Ulrich CM, White E, Xiang Y, Zanke BW, Zeng YX, Zhang B, Zheng W, Hsu L; Colon Cancer Family Registry and the Genetics and Epidemiology of Colorectal Cancer Consortium. Peters U, et al. Gastroenterology. 2013 Apr;144(4):799-807.e24. doi: 10.1053/j.gastro.2012.12.020. Epub 2012 Dec 22. Gastroenterology. 2013. PMID: 23266556 Free PMC article. Review.
See all similar articles

Cited by 96 articles

See all "Cited by" articles

References

    1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. - PubMed
    1. Ferlay J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur J Cancer. 2013;49:1374–1403. - PubMed
    1. Hidalgo M. Pancreatic cancer. N Engl J Med. 2010;362:1605–1617. - PubMed
    1. Klein AP. Genetic susceptibility to pancreatic cancer. Mol Carcinog. 2012;51:14–24. - PMC - PubMed
    1. Amundadottir L, et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet. 2009;41:986–990. - PMC - PubMed

Publication types

Grant support

Feedback