A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

Gloria M. Petersen; Laufey Amundadottir; Charles S. Fuchs; Peter Kraft; Rachael Z. Stolzenberg-Solomon; Kevin B. Jacobs; Alan A. Arslan; H. Bas Bueno-De-Mesquita; Steven Gallinger; Myron Gross; Kathy Helzlsouer; Elizabeth A. Holly; Eric J. Jacobs; Alison P. Klein; Andrea Lacroix; Donghui Li; Margaret T. Mandelson; Sara H. Olson; Harvey A. Risch; Wei Zheng; Demetrius Albanes; William R. Bamlet; Christine D. Berg; Marie Christine Boutron-Ruault; Julie E. Buring; Paige M. Bracci; Federico Canzian; Sandra Clipp; Michelle Cotterchio; Mariza De Andrade; Eric J. Duell; J. Michael Gaziano; Edward L. Giovannucci; Michael Goggins; Göran Hallmans; Susan E. Hankinson; Manal Hassan; Barbara Howard; David J. Hunter; Amy Hutchinson; Mazda Jenab; Rudolf Kaaks; Charles Kooperberg; Vittorio Krogh; Robert C. Kurtz; Shannon M. Lynch; Robert R. McWilliams; Julie B. Mendelsohn; Dominique S. Michaud; Hemang Parikh; Alpa V. Patel; Petra H.M. Peeters; Aleksandar Rajkovic; Elio Riboli; Laudina Rodriguez; Daniela Seminara; Xiao Ou Shu; Gilles Thomas; Anne Tjønneland; Geoffrey S. Tobias; Dimitrios Trichopoulos; Stephen K. Van Den Eeden; Jarmo Virtamo; Jean Wactawski-Wende; Zhaoming Wang; Brian M. Wolpin; Herbert Yu; Kai Yu; Anne Zeleniuch-Jacquotte; Joseph F. Fraumeni; Robert N. Hoover; Patricia Hartge; Stephen J. Chanock

doi:10.1038/ng.522

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

Gloria M. Petersen, Laufey Amundadottir, Charles S. Fuchs, Peter Kraft, Rachael Z. Stolzenberg-Solomon, Kevin B. Jacobs, Alan A. Arslan, H. Bas Bueno-De-Mesquita, Steven Gallinger, Myron Gross, Kathy Helzlsouer, Elizabeth A. Holly, Eric J. Jacobs, Alison P. Klein, Andrea Lacroix, Donghui Li, Margaret T. Mandelson, Sara H. Olson, Harvey A. Risch, Wei ZhengDemetrius Albanes, William R. Bamlet, Christine D. Berg, Marie Christine Boutron-Ruault, Julie E. Buring, Paige M. Bracci, Federico Canzian, Sandra Clipp, Michelle Cotterchio, Mariza De Andrade, Eric J. Duell, J. Michael Gaziano, Edward L. Giovannucci, Michael Goggins, Göran Hallmans, Susan E. Hankinson, Manal Hassan, Barbara Howard, David J. Hunter, Amy Hutchinson, Mazda Jenab, Rudolf Kaaks, Charles Kooperberg, Vittorio Krogh, Robert C. Kurtz, Shannon M. Lynch, Robert R. McWilliams, Julie B. Mendelsohn, Dominique S. Michaud, Hemang Parikh, Alpa V. Patel, Petra H.M. Peeters, Aleksandar Rajkovic, Elio Riboli, Laudina Rodriguez, Daniela Seminara, Xiao Ou Shu, Gilles Thomas, Anne Tjønneland, Geoffrey S. Tobias, Dimitrios Trichopoulos, Stephen K. Van Den Eeden, Jarmo Virtamo, Jean Wactawski-Wende, Zhaoming Wang, Brian M. Wolpin, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Joseph F. Fraumeni, Robert N. Hoover, Patricia Hartge, Stephen J. Chanock

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Abstract

We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10 11, per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 × 10 8, per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10 10, per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 × 10 7, per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

Original language	English
Pages (from-to)	224-228
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	3
DOIs	https://doi.org/10.1038/ng.522
State	Published - Mar 2010
Externally published	Yes

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10.1038/ng.522

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Petersen, G. M., Amundadottir, L., Fuchs, C. S., Kraft, P., Stolzenberg-Solomon, R. Z., Jacobs, K. B., Arslan, A. A., Bueno-De-Mesquita, H. B., Gallinger, S., Gross, M., Helzlsouer, K., Holly, E. A., Jacobs, E. J., Klein, A. P., Lacroix, A., Li, D., Mandelson, M. T., Olson, S. H., Risch, H. A., ... Chanock, S. J. (2010). A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nature Genetics, 42(3), 224-228. https://doi.org/10.1038/ng.522

@article{879ef139b9504eed884fdbe67d23d996,

title = "A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33",

abstract = "We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10 11, per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 × 10 8, per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10 10, per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 × 10 7, per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.",

author = "Petersen, {Gloria M.} and Laufey Amundadottir and Fuchs, {Charles S.} and Peter Kraft and Stolzenberg-Solomon, {Rachael Z.} and Jacobs, {Kevin B.} and Arslan, {Alan A.} and Bueno-De-Mesquita, {H. Bas} and Steven Gallinger and Myron Gross and Kathy Helzlsouer and Holly, {Elizabeth A.} and Jacobs, {Eric J.} and Klein, {Alison P.} and Andrea Lacroix and Donghui Li and Mandelson, {Margaret T.} and Olson, {Sara H.} and Risch, {Harvey A.} and Wei Zheng and Demetrius Albanes and Bamlet, {William R.} and Berg, {Christine D.} and Boutron-Ruault, {Marie Christine} and Buring, {Julie E.} and Bracci, {Paige M.} and Federico Canzian and Sandra Clipp and Michelle Cotterchio and {De Andrade}, Mariza and Duell, {Eric J.} and Gaziano, {J. Michael} and Giovannucci, {Edward L.} and Michael Goggins and G{\"o}ran Hallmans and Hankinson, {Susan E.} and Manal Hassan and Barbara Howard and Hunter, {David J.} and Amy Hutchinson and Mazda Jenab and Rudolf Kaaks and Charles Kooperberg and Vittorio Krogh and Kurtz, {Robert C.} and Lynch, {Shannon M.} and McWilliams, {Robert R.} and Mendelsohn, {Julie B.} and Michaud, {Dominique S.} and Hemang Parikh and Patel, {Alpa V.} and Peeters, {Petra H.M.} and Aleksandar Rajkovic and Elio Riboli and Laudina Rodriguez and Daniela Seminara and Shu, {Xiao Ou} and Gilles Thomas and Anne Tj{\o}nneland and Tobias, {Geoffrey S.} and Dimitrios Trichopoulos and {Van Den Eeden}, {Stephen K.} and Jarmo Virtamo and Jean Wactawski-Wende and Zhaoming Wang and Wolpin, {Brian M.} and Herbert Yu and Kai Yu and Anne Zeleniuch-Jacquotte and Fraumeni, {Joseph F.} and Hoover, {Robert N.} and Patricia Hartge and Chanock, {Stephen J.}",

year = "2010",

month = mar,

doi = "10.1038/ng.522",

language = "English",

volume = "42",

pages = "224--228",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "3",

}

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, PHM, 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, Hoover, RN, Hartge, P & Chanock, SJ 2010, 'A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33', Nature Genetics, vol. 42, no. 3, pp. 224-228. https://doi.org/10.1038/ng.522

TY - JOUR

T1 - A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

AU - Petersen, Gloria M.

AU - Amundadottir, Laufey

AU - Fuchs, Charles S.

AU - Kraft, Peter

AU - Stolzenberg-Solomon, Rachael Z.

AU - Jacobs, Kevin B.

AU - Arslan, Alan A.

AU - Bueno-De-Mesquita, H. Bas

AU - Gallinger, Steven

AU - Gross, Myron

AU - Helzlsouer, Kathy

AU - Holly, Elizabeth A.

AU - Jacobs, Eric J.

AU - Klein, Alison P.

AU - Lacroix, Andrea

AU - Li, Donghui

AU - Mandelson, Margaret T.

AU - Olson, Sara H.

AU - Risch, Harvey A.

AU - Zheng, Wei

AU - Albanes, Demetrius

AU - Bamlet, William R.

AU - Berg, Christine D.

AU - Boutron-Ruault, Marie Christine

AU - Buring, Julie E.

AU - Bracci, Paige M.

AU - Canzian, Federico

AU - Clipp, Sandra

AU - Cotterchio, Michelle

AU - De Andrade, Mariza

AU - Duell, Eric J.

AU - Gaziano, J. Michael

AU - Giovannucci, Edward L.

AU - Goggins, Michael

AU - Hallmans, Göran

AU - Hankinson, Susan E.

AU - Hassan, Manal

AU - Howard, Barbara

AU - Hunter, David J.

AU - Hutchinson, Amy

AU - Jenab, Mazda

AU - Kaaks, Rudolf

AU - Kooperberg, Charles

AU - Krogh, Vittorio

AU - Kurtz, Robert C.

AU - Lynch, Shannon M.

AU - McWilliams, Robert R.

AU - Mendelsohn, Julie B.

AU - Michaud, Dominique S.

AU - Parikh, Hemang

AU - Patel, Alpa V.

AU - Peeters, Petra H.M.

AU - Rajkovic, Aleksandar

AU - Riboli, Elio

AU - Rodriguez, Laudina

AU - Seminara, Daniela

AU - Shu, Xiao Ou

AU - Thomas, Gilles

AU - Tjønneland, Anne

AU - Tobias, Geoffrey S.

AU - Trichopoulos, Dimitrios

AU - Van Den Eeden, Stephen K.

AU - Virtamo, Jarmo

AU - Wactawski-Wende, Jean

AU - Wang, Zhaoming

AU - Wolpin, Brian M.

AU - Yu, Herbert

AU - Yu, Kai

AU - Zeleniuch-Jacquotte, Anne

AU - Fraumeni, Joseph F.

AU - Hoover, Robert N.

AU - Hartge, Patricia

AU - Chanock, Stephen J.

PY - 2010/3

Y1 - 2010/3

N2 - We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10 11, per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 × 10 8, per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10 10, per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 × 10 7, per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

AB - We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10 11, per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 × 10 8, per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10 10, per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 × 10 7, per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

UR - http://www.scopus.com/inward/record.url?scp=77649188501&partnerID=8YFLogxK

U2 - 10.1038/ng.522

DO - 10.1038/ng.522

M3 - Article

C2 - 20101243

AN - SCOPUS:77649188501

SN - 1061-4036

VL - 42

SP - 224

EP - 228

JO - Nature Genetics

JF - Nature Genetics

IS - 3

ER -

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33

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