The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma

Summer S. Han; Meredith Yeager; Lee E. Moore; Ming Hui Wei; Ruth Pfeiffer; Ousmane Toure; Mark P. Purdue; Mattias Johansson; Ghislaine Scelo; Charles C. Chung; Valerie Gaborieau; David Zaridze; Kendra Schwartz; Neonilia Szeszenia-Dabrowska; Faith Davis; Vladimir Bencko; Joanne S. Colt; Vladimir Janout; Vsevolod Matveev; Lenka Foretova; Dana Mates; M. Navratilova; Paolo Boffetta; Christine D. Berg; Robert L. Grubb; Victoria L. Stevens; Michael J. Thun; W. Ryan Diver; Susan M. Gapstur; Demetrius Albanes; Stephanie J. Weinstein; Jarmo Virtamo; Laurie Burdett; Antonin Brisuda; James D. McKay; Joseph F. Fraumeni; Nilanjan Chatterjee; Philip S. Rosenberg; Nathaniel Rothman; Paul Brennan; Wong Ho Chow; Margaret A. Tucker; Stephen J. Chanock; Jorge R. Toro

doi:10.1093/hmg/ddr551

The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma

Summer S. Han, Meredith Yeager, Lee E. Moore, Ming Hui Wei, Ruth Pfeiffer, Ousmane Toure, Mark P. Purdue, Mattias Johansson, Ghislaine Scelo, Charles C. Chung, Valerie Gaborieau, David Zaridze, Kendra Schwartz, Neonilia Szeszenia-Dabrowska, Faith Davis, Vladimir Bencko, Joanne S. Colt, Vladimir Janout, Vsevolod Matveev, Lenka ForetovaDana Mates, M. Navratilova, Paolo Boffetta, Christine D. Berg, Robert L. Grubb, Victoria L. Stevens, Michael J. Thun, W. Ryan Diver, Susan M. Gapstur, Demetrius Albanes, Stephanie J. Weinstein, Jarmo Virtamo, Laurie Burdett, Antonin Brisuda, James D. McKay, Joseph F. Fraumeni, Nilanjan Chatterjee, Philip S. Rosenberg, Nathaniel Rothman, Paul Brennan, Wong Ho Chow, Margaret A. Tucker, Stephen J. Chanock, Jorge R. Toro

Research output: Contribution to journal › Article › peer-review

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Abstract

In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P=5 5.75× 3 10 ^-8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10 ^-14) and rs12617313 (P = 7.48 × 10 ^-12), both highly correlated withrs9679290 (r ² > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r ² < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10 ^-9, per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. Published by Oxford University Press 2011.

Original language	English (US)
Article number	ddr551
Pages (from-to)	1190-1200
Number of pages	11
Journal	Human molecular genetics
Volume	21
Issue number	5
DOIs	https://doi.org/10.1093/hmg/ddr551
State	Published - Mar 2012
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Han, S. S., Yeager, M., Moore, L. E., Wei, M. H., Pfeiffer, R., Toure, O., Purdue, M. P., Johansson, M., Scelo, G., Chung, C. C., Gaborieau, V., Zaridze, D., Schwartz, K., Szeszenia-Dabrowska, N., Davis, F., Bencko, V., Colt, J. S., Janout, V., Matveev, V., ... Toro, J. R. (2012). The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma. Human molecular genetics, 21(5), 1190-1200. Article ddr551. https://doi.org/10.1093/hmg/ddr551

Han, SS, Yeager, M, Moore, LE, Wei, MH, Pfeiffer, R, Toure, O, Purdue, MP, Johansson, M, Scelo, G, Chung, CC, Gaborieau, V, Zaridze, D, Schwartz, K, Szeszenia-Dabrowska, N, Davis, F, Bencko, V, Colt, JS, Janout, V, Matveev, V, Foretova, L, Mates, D, Navratilova, M, Boffetta, P, Berg, CD, Grubb, RL, Stevens, VL, Thun, MJ, Diver, WR, Gapstur, SM, Albanes, D, Weinstein, SJ, Virtamo, J, Burdett, L, Brisuda, A, McKay, JD, Fraumeni, JF, Chatterjee, N, Rosenberg, PS, Rothman, N, Brennan, P, Chow, WH, Tucker, MA, Chanock, SJ & Toro, JR 2012, 'The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma', Human molecular genetics, vol. 21, no. 5, ddr551, pp. 1190-1200. https://doi.org/10.1093/hmg/ddr551

@article{be97d1e7cc7245d98e0f25e9b9ac7d4a,

title = "The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma",

abstract = "In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P=5 5.75× 3 10 -8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10 -14) and rs12617313 (P = 7.48 × 10 -12), both highly correlated withrs9679290 (r 2 > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r 2 < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10 -9, per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. Published by Oxford University Press 2011.",

author = "Han, {Summer S.} and Meredith Yeager and Moore, {Lee E.} and Wei, {Ming Hui} and Ruth Pfeiffer and Ousmane Toure and Purdue, {Mark P.} and Mattias Johansson and Ghislaine Scelo and Chung, {Charles C.} and Valerie Gaborieau and David Zaridze and Kendra Schwartz and Neonilia Szeszenia-Dabrowska and Faith Davis and Vladimir Bencko and Colt, {Joanne S.} and Vladimir Janout and Vsevolod Matveev and Lenka Foretova and Dana Mates and M. Navratilova and Paolo Boffetta and Berg, {Christine D.} and Grubb, {Robert L.} and Stevens, {Victoria L.} and Thun, {Michael J.} and Diver, {W. Ryan} and Gapstur, {Susan M.} and Demetrius Albanes and Weinstein, {Stephanie J.} and Jarmo Virtamo and Laurie Burdett and Antonin Brisuda and McKay, {James D.} and Fraumeni, {Joseph F.} and Nilanjan Chatterjee and Rosenberg, {Philip S.} and Nathaniel Rothman and Paul Brennan and Chow, {Wong Ho} and Tucker, {Margaret A.} and Chanock, {Stephen J.} and Toro, {Jorge R.}",

note = "Funding Information: This research was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA, and by European Commission INCOCOPERNICUS grant IC15-CT96-0313.",

year = "2012",

month = mar,

doi = "10.1093/hmg/ddr551",

language = "English (US)",

volume = "21",

pages = "1190--1200",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "5",

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T1 - The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma

AU - Han, Summer S.

AU - Yeager, Meredith

AU - Moore, Lee E.

AU - Wei, Ming Hui

AU - Pfeiffer, Ruth

AU - Toure, Ousmane

AU - Purdue, Mark P.

AU - Johansson, Mattias

AU - Scelo, Ghislaine

AU - Chung, Charles C.

AU - Gaborieau, Valerie

AU - Zaridze, David

AU - Schwartz, Kendra

AU - Szeszenia-Dabrowska, Neonilia

AU - Davis, Faith

AU - Bencko, Vladimir

AU - Colt, Joanne S.

AU - Janout, Vladimir

AU - Matveev, Vsevolod

AU - Foretova, Lenka

AU - Mates, Dana

AU - Navratilova, M.

AU - Boffetta, Paolo

AU - Berg, Christine D.

AU - Grubb, Robert L.

AU - Stevens, Victoria L.

AU - Thun, Michael J.

AU - Diver, W. Ryan

AU - Gapstur, Susan M.

AU - Albanes, Demetrius

AU - Weinstein, Stephanie J.

AU - Virtamo, Jarmo

AU - Burdett, Laurie

AU - Brisuda, Antonin

AU - McKay, James D.

AU - Fraumeni, Joseph F.

AU - Chatterjee, Nilanjan

AU - Rosenberg, Philip S.

AU - Rothman, Nathaniel

AU - Brennan, Paul

AU - Chow, Wong Ho

AU - Tucker, Margaret A.

AU - Chanock, Stephen J.

AU - Toro, Jorge R.

N1 - Funding Information: This research was supported in part by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, USA, and by European Commission INCOCOPERNICUS grant IC15-CT96-0313.

PY - 2012/3

Y1 - 2012/3

N2 - In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P=5 5.75× 3 10 -8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10 -14) and rs12617313 (P = 7.48 × 10 -12), both highly correlated withrs9679290 (r 2 > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r 2 < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10 -9, per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. Published by Oxford University Press 2011.

AB - In follow-up of a recent genome-wide association study (GWAS) that identified a locus in chromosome 2p21 associated with risk for renal cell carcinoma (RCC), we conducted a fine mapping analysis of a 120 kb region that includes EPAS1. We genotyped 59 tagged common single-nucleotide polymorphisms (SNPs) in 2278 RCC and 3719 controls of European background and observed a novel signal for rs9679290 [P=5 5.75× 3 10 -8, per-allele odds ratio (OR) = 1.27, 95% confidence interval (CI): 1.17-1.39]. Imputation of common SNPs surrounding rs9679290 using HapMap 3 and 1000 Genomes data yielded two additional signals, rs4953346 (P = 4.09 × 10 -14) and rs12617313 (P = 7.48 × 10 -12), both highly correlated withrs9679290 (r 2 > 0.95), but interestingly not correlated with the two SNPs reported in the GWAS: rs11894252 and rs7579899 (r 2 < 0.1 with rs9679290). Genotype analysis of rs12617313 confirmed an association with RCC risk (P = 1.72 × 10 -9, per-allele OR = 1.28, 95% CI: 1.18-1.39) In conclusion, we report that chromosome 2p21 harbors a complex genetic architecture for common RCC risk variants. Published by Oxford University Press 2011.

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The chromosome 2p21 region harbors a complex genetic architecture for association with risk for renal cell carcinoma

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