A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

Xifeng Wu; Ghislaine Scelo; Mark P. Purdue; Nathaniel Rothman; Mattias Johansson; Yuanqing Ye; Zhaoming Wang; Diana Zelenika; Lee E. Moore; Christopher G. Wood; Egor Prokhortchouk; Valerie Gaborieau; Kevin B. Jacobs; Wong Ho Chow; Jorge R. Toro; David Zaridze; Jie Lin; Jan Lubinski; Joanna Trubicka; Neonilia Szeszenia-dabrowska; Jolanta Lissowska; Peter Rudnai; Eleonora Fabianova; Dana Mates; Viorel Jinga; Vladimir Bencko; Alena Slamova; Ivana Holcatova; Marie Navratilova; Vladimir Janout; Paolo Boffetta; Joanne S. Colt; Faith G. Davis; Kendra L. Schwartz; Rosamonde E. Banks; Peter J. Selby; Patricia Harnden; Christine D. Berg; Ann W. Hsing; III L. Grubb Robert L.; Heiner Boeing; Paolo Vineis; Françoise Clavel-chapelon; Domenico Palli; Rosario Tumino; Vittorio Krogh; Salvatore Panico; Eric J. Duell; José Ramón Quirós; Maria José Sanchez; Carmen Navarro; Eva Ardanaz; Miren Dorronsoro; Kay Tee Khaw; Naomi E. Allen; H. Bas Bueno-de-mesquita; Petra H.M. Peeters; Dimitrios Trichopoulos; Jakob Linseisen; Börje Ljungberg; Kim Overvad; Anne Tjonneland; Isabelle Romieu; Elio Riboli; Victoria L. Stevens; Michael J. Thun; W. Ryan Diver; Susan M. Gapstur; Paul D. Pharoah; Douglas F. Easton; Demetrius Albanes; Jarmo Virtamo; Lars Vatten; Kristian Hveem; Tony Fletcher; Kvetoslava Koppova; Olivier Cussenot; Geraldine Cancel-tassin; Simone Benhamou; Michelle A. Hildebrandt; Xia Pu; Mario Foglio; Doris Lechner; Amy Hutchinson; Meredith Yeager; Joseph F. Fraumeni; Mark Lathrop; Konstantin G. Skryabin; James D. McKay; Jian Gu; Paul Brennan; Stephen J. Chanock

doi:10.1093/hmg/ddr479

A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

Xifeng Wu, Ghislaine Scelo, Mark P. Purdue, Nathaniel Rothman, Mattias Johansson, Yuanqing Ye, Zhaoming Wang, Diana Zelenika, Lee E. Moore, Christopher G. Wood, Egor Prokhortchouk, Valerie Gaborieau, Kevin B. Jacobs, Wong Ho Chow, Jorge R. Toro, David Zaridze, Jie Lin, Jan Lubinski, Joanna Trubicka, Neonilia Szeszenia-dabrowskaJolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Viorel Jinga, Vladimir Bencko, Alena Slamova, Ivana Holcatova, Marie Navratilova, Vladimir Janout, Paolo Boffetta, Joanne S. Colt, Faith G. Davis, Kendra L. Schwartz, Rosamonde E. Banks, Peter J. Selby, Patricia Harnden, Christine D. Berg, Ann W. Hsing, III L. Grubb Robert L., Heiner Boeing, Paolo Vineis, Françoise Clavel-chapelon, Domenico Palli, Rosario Tumino, Vittorio Krogh, Salvatore Panico, Eric J. Duell, José Ramón Quirós, Maria José Sanchez, Carmen Navarro, Eva Ardanaz, Miren Dorronsoro, Kay Tee Khaw, Naomi E. Allen, H. Bas Bueno-de-mesquita, Petra H.M. Peeters, Dimitrios Trichopoulos, Jakob Linseisen, Börje Ljungberg, Kim Overvad, Anne Tjonneland, Isabelle Romieu, Elio Riboli, Victoria L. Stevens, Michael J. Thun, W. Ryan Diver, Susan M. Gapstur, Paul D. Pharoah, Douglas F. Easton, Demetrius Albanes, Jarmo Virtamo, Lars Vatten, Kristian Hveem, Tony Fletcher, Kvetoslava Koppova, Olivier Cussenot, Geraldine Cancel-tassin, Simone Benhamou, Michelle A. Hildebrandt, Xia Pu, Mario Foglio, Doris Lechner, Amy Hutchinson, Meredith Yeager, Joseph F. Fraumeni, Mark Lathrop, Konstantin G. Skryabin, James D. McKay, Jian Gu, Paul Brennan, Stephen J. Chanock

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

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Abstract

Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r² = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10^-10 and P = 6.07 × 10^-9, respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.

Original language	English (US)
Pages (from-to)	456-462
Number of pages	7
Journal	Human molecular genetics
Volume	21
Issue number	2
DOIs	https://doi.org/10.1093/hmg/ddr479
State	Published - Jan 2012
Externally published	Yes

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Wu, X., Scelo, G., Purdue, M. P., Rothman, N., Johansson, M., Ye, Y., Wang, Z., Zelenika, D., Moore, L. E., Wood, C. G., Prokhortchouk, E., Gaborieau, V., Jacobs, K. B., Chow, W. H., Toro, J. R., Zaridze, D., Lin, J., Lubinski, J., Trubicka, J., ... Chanock, S. J. (2012). A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23. Human molecular genetics, 21(2), 456-462. https://doi.org/10.1093/hmg/ddr479

Wu, X, Scelo, G, Purdue, MP, Rothman, N, Johansson, M, Ye, Y, Wang, Z, Zelenika, D, Moore, LE, Wood, CG, Prokhortchouk, E, Gaborieau, V, Jacobs, KB, Chow, WH, Toro, JR, Zaridze, D, Lin, J, Lubinski, J, Trubicka, J, Szeszenia-dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Mates, D, Jinga, V, Bencko, V, Slamova, A, Holcatova, I, Navratilova, M, Janout, V, Boffetta, P, Colt, JS, Davis, FG, Schwartz, KL, Banks, RE, Selby, PJ, Harnden, P, Berg, CD, Hsing, AW, Grubb Robert L., IIIL, Boeing, H, Vineis, P, Clavel-chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, S, Duell, EJ, Quirós, JR, Sanchez, MJ, Navarro, C, Ardanaz, E, Dorronsoro, M, Khaw, KT, Allen, NE, Bueno-de-mesquita, HB, Peeters, PHM, Trichopoulos, D, Linseisen, J, Ljungberg, B, Overvad, K, Tjonneland, A, Romieu, I, Riboli, E, Stevens, VL, Thun, MJ, Diver, WR, Gapstur, SM, Pharoah, PD, Easton, DF, Albanes, D, Virtamo, J, Vatten, L, Hveem, K, Fletcher, T, Koppova, K, Cussenot, O, Cancel-tassin, G, Benhamou, S, Hildebrandt, MA, Pu, X, Foglio, M, Lechner, D, Hutchinson, A, Yeager, M, Fraumeni, JF, Lathrop, M, Skryabin, KG, McKay, JD, Gu, J, Brennan, P & Chanock, SJ 2012, 'A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23', Human molecular genetics, vol. 21, no. 2, pp. 456-462. https://doi.org/10.1093/hmg/ddr479

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title = "A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23",

abstract = "Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r2 = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10-10 and P = 6.07 × 10-9, respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.",

author = "Xifeng Wu and Ghislaine Scelo and Purdue, {Mark P.} and Nathaniel Rothman and Mattias Johansson and Yuanqing Ye and Zhaoming Wang and Diana Zelenika and Moore, {Lee E.} and Wood, {Christopher G.} and Egor Prokhortchouk and Valerie Gaborieau and Jacobs, {Kevin B.} and Chow, {Wong Ho} and Toro, {Jorge R.} and David Zaridze and Jie Lin and Jan Lubinski and Joanna Trubicka and Neonilia Szeszenia-dabrowska and Jolanta Lissowska and Peter Rudnai and Eleonora Fabianova and Dana Mates and Viorel Jinga and Vladimir Bencko and Alena Slamova and Ivana Holcatova and Marie Navratilova and Vladimir Janout and Paolo Boffetta and Colt, {Joanne S.} and Davis, {Faith G.} and Schwartz, {Kendra L.} and Banks, {Rosamonde E.} and Selby, {Peter J.} and Patricia Harnden and Berg, {Christine D.} and Hsing, {Ann W.} and {Grubb Robert L.}, {III L.} and Heiner Boeing and Paolo Vineis and Fran{\c c}oise Clavel-chapelon and Domenico Palli and Rosario Tumino and Vittorio Krogh and Salvatore Panico and Duell, {Eric J.} and Quir{\'o}s, {Jos{\'e} Ram{\'o}n} and Sanchez, {Maria Jos{\'e}} and Carmen Navarro and Eva Ardanaz and Miren Dorronsoro and Khaw, {Kay Tee} and Allen, {Naomi E.} and Bueno-de-mesquita, {H. Bas} and Peeters, {Petra H.M.} and Dimitrios Trichopoulos and Jakob Linseisen and B{\"o}rje Ljungberg and Kim Overvad and Anne Tjonneland and Isabelle Romieu and Elio Riboli and Stevens, {Victoria L.} and Thun, {Michael J.} and Diver, {W. Ryan} and Gapstur, {Susan M.} and Pharoah, {Paul D.} and Easton, {Douglas F.} and Demetrius Albanes and Jarmo Virtamo and Lars Vatten and Kristian Hveem and Tony Fletcher and Kvetoslava Koppova and Olivier Cussenot and Geraldine Cancel-tassin and Simone Benhamou and Hildebrandt, {Michelle A.} and Xia Pu and Mario Foglio and Doris Lechner and Amy Hutchinson and Meredith Yeager and Fraumeni, {Joseph F.} and Mark Lathrop and Skryabin, {Konstantin G.} and McKay, {James D.} and Jian Gu and Paul Brennan and Chanock, {Stephen J.}",

note = "Funding Information: The study was partially supported by the US National Institutes of Health (NIH) grant R01CA 98897 (X.W.), MD Anderson Research Trust (X.W.), French Institut National du Cancer (INCa) for those studies coordinated by IARC/ CNG and the intramural research program of the National Cancer Institute (NCI), NIH for those studies coordinated by the NCI.",

year = "2012",

month = jan,

doi = "10.1093/hmg/ddr479",

language = "English (US)",

volume = "21",

pages = "456--462",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "2",

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TY - JOUR

T1 - A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

AU - Wu, Xifeng

AU - Scelo, Ghislaine

AU - Purdue, Mark P.

AU - Rothman, Nathaniel

AU - Johansson, Mattias

AU - Ye, Yuanqing

AU - Wang, Zhaoming

AU - Zelenika, Diana

AU - Moore, Lee E.

AU - Wood, Christopher G.

AU - Prokhortchouk, Egor

AU - Gaborieau, Valerie

AU - Jacobs, Kevin B.

AU - Chow, Wong Ho

AU - Toro, Jorge R.

AU - Zaridze, David

AU - Lin, Jie

AU - Lubinski, Jan

AU - Trubicka, Joanna

AU - Szeszenia-dabrowska, Neonilia

AU - Lissowska, Jolanta

AU - Rudnai, Peter

AU - Fabianova, Eleonora

AU - Mates, Dana

AU - Jinga, Viorel

AU - Bencko, Vladimir

AU - Slamova, Alena

AU - Holcatova, Ivana

AU - Navratilova, Marie

AU - Janout, Vladimir

AU - Boffetta, Paolo

AU - Colt, Joanne S.

AU - Davis, Faith G.

AU - Schwartz, Kendra L.

AU - Banks, Rosamonde E.

AU - Selby, Peter J.

AU - Harnden, Patricia

AU - Berg, Christine D.

AU - Hsing, Ann W.

AU - Grubb Robert L., III L.

AU - Boeing, Heiner

AU - Vineis, Paolo

AU - Clavel-chapelon, Françoise

AU - Palli, Domenico

AU - Tumino, Rosario

AU - Krogh, Vittorio

AU - Panico, Salvatore

AU - Duell, Eric J.

AU - Quirós, José Ramón

AU - Sanchez, Maria José

AU - Navarro, Carmen

AU - Ardanaz, Eva

AU - Dorronsoro, Miren

AU - Khaw, Kay Tee

AU - Allen, Naomi E.

AU - Bueno-de-mesquita, H. Bas

AU - Peeters, Petra H.M.

AU - Trichopoulos, Dimitrios

AU - Linseisen, Jakob

AU - Ljungberg, Börje

AU - Overvad, Kim

AU - Tjonneland, Anne

AU - Romieu, Isabelle

AU - Riboli, Elio

AU - Stevens, Victoria L.

AU - Thun, Michael J.

AU - Diver, W. Ryan

AU - Gapstur, Susan M.

AU - Pharoah, Paul D.

AU - Easton, Douglas F.

AU - Albanes, Demetrius

AU - Virtamo, Jarmo

AU - Vatten, Lars

AU - Hveem, Kristian

AU - Fletcher, Tony

AU - Koppova, Kvetoslava

AU - Cussenot, Olivier

AU - Cancel-tassin, Geraldine

AU - Benhamou, Simone

AU - Hildebrandt, Michelle A.

AU - Pu, Xia

AU - Foglio, Mario

AU - Lechner, Doris

AU - Hutchinson, Amy

AU - Yeager, Meredith

AU - Fraumeni, Joseph F.

AU - Lathrop, Mark

AU - Skryabin, Konstantin G.

AU - McKay, James D.

AU - Gu, Jian

AU - Brennan, Paul

AU - Chanock, Stephen J.

N1 - Funding Information: The study was partially supported by the US National Institutes of Health (NIH) grant R01CA 98897 (X.W.), MD Anderson Research Trust (X.W.), French Institut National du Cancer (INCa) for those studies coordinated by IARC/ CNG and the intramural research program of the National Cancer Institute (NCI), NIH for those studies coordinated by the NCI.

PY - 2012/1

Y1 - 2012/1

N2 - Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r2 = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10-10 and P = 6.07 × 10-9, respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.

AB - Renal cell carcinoma (RCC) is the most lethal urologic cancer. Only two common susceptibility loci for RCC have been confirmed to date. To identify additional RCC common susceptibility loci, we conducted an independent genome-wide association study (GWAS). We analyzed 533 191 single nucleotide polymorphisms (SNPs) for association with RCC in 894 cases and 1516 controls of European descent recruited from MD Anderson Cancer Center in the primary scan, and validated the top 500 SNPs in silico in 3772 cases and 8505 controls of European descent involved in the only published GWAS of RCC. We identified two common variants in linkage disequilibrium, rs718314 and rs1049380 (r2 = 0.64, D ' = 0.84), in the inositol 1,4,5-triphosphate receptor, type 2 (ITPR2) gene on 12p11.23 as novel susceptibility loci for RCC (P = 8.89 × 10-10 and P = 6.07 × 10-9, respectively, in meta-analysis) with an allelic odds ratio of 1.19 [95% confidence interval (CI): 1.13-1.26] for rs718314 and 1.18 (95% CI: 1.12-1.25) for rs1049380. It has been recently identified that rs718314 in ITPR2 is associated with waist-hip ratio (WHR) phenotype. To our knowledge, this is the first genetic locus associated with both cancer risk and WHR.

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DO - 10.1093/hmg/ddr479

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EP - 462

JO - Human molecular genetics

JF - Human molecular genetics

IS - 2

ER -

A genome-wide association study identifies a novel susceptibility locus for renal cell carcinoma on 12p11.23

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