Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma

Mitchell J. Machiela; Jonathan N. Hofmann; Robert Carreras-Torres; Kevin M. Brown; Mattias Johansson; Zhaoming Wang; Matthieu Foll; Peng Li; Nathaniel Rothman; Sharon A. Savage; Valerie Gaborieau; James D. McKay; Yuanqing Ye; Marc Henrion; Fiona Bruinsma; Susan Jordan; Gianluca Severi; Kristian Hveem; Lars J. Vatten; Tony Fletcher; Kvetoslava Koppova; Susanna C. Larsson; Alicja Wolk; Rosamonde E. Banks; Peter J. Selby; Douglas F. Easton; Paul Pharoah; Gabriella Andreotti; Laura E.Beane Freeman; Stella Koutros; Demetrius Albanes; Satu Mannisto; Stephanie Weinstein; Peter E. Clark; Todd E. Edwards; Loren Lipworth; Susan M. Gapstur; Victoria L. Stevens; Hallie Carol; Matthew L. Freedman; Mark M. Pomerantz; Eunyoung Cho; Peter Kraft; Mark A. Preston; Kathryn M. Wilson; J. Michael Gaziano; Howard S. Sesso; Amanda Black; Neal D. Freedman; Wen Yi Huang; John G. Anema; Richard J. Kahnoski; Brian R. Lane; Sabrina L. Noyes; David Petillo; Leandro M. Colli; Joshua N. Sampson; Celine Besse; Helene Blanche; Anne Boland; Laurie Burdette; Egor Prokhortchouk; Konstantin G. Skryabin; Meredith Yeager; Mirjana Mijuskovic; Miodrag Ognjanovic; Lenka Foretova; Ivana Holcatova; Vladimir Janout; Dana Mates; Anush Mukeriya; Stefan Rascu; David Zaridze; Vladimir Bencko; Cezary Cybulski; Eleonora Fabianova; Viorel Jinga; Jolanta Lissowska; Jan Lubinski; Marie Navratilova; Peter Rudnai; Neonila Szeszenia-Dabrowska; Simone Benhamou; Geraldine Cancel-Tassin; Olivier Cussenot; H. Bas Bueno-de-Mesquita; Federico Canzian; Eric J. Duell; Börje Ljungberg; Raviprakash T. Sitaram; Ulrike Peters; Emily White; Garnet L. Anderson; Lisa Johnson; Juhua Luo; Julie Buring; I. Min Lee; Wong Ho Chow; Lee E. Moore; Christopher Wood; Timothy Eisen; James Larkin; Toni K. Choueiri; G. Mark Lathrop; Bin Tean Teh; Jean Francois Deleuze; Xifeng Wu; Richard S. Houlston; Paul Brennan; Stephen J. Chanock; Ghislaine Scelo; Mark P. Purdue

doi:10.1016/j.eururo.2017.07.015

Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma

Mitchell J. Machiela, Jonathan N. Hofmann, Robert Carreras-Torres, Kevin M. Brown, Mattias Johansson, Zhaoming Wang, Matthieu Foll, Peng Li, Nathaniel Rothman, Sharon A. Savage, Valerie Gaborieau, James D. McKay, Yuanqing Ye, Marc Henrion, Fiona Bruinsma, Susan Jordan, Gianluca Severi, Kristian Hveem, Lars J. Vatten, Tony FletcherKvetoslava Koppova, Susanna C. Larsson, Alicja Wolk, Rosamonde E. Banks, Peter J. Selby, Douglas F. Easton, Paul Pharoah, Gabriella Andreotti, Laura E.Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Mannisto, Stephanie Weinstein, Peter E. Clark, Todd E. Edwards, Loren Lipworth, Susan M. Gapstur, Victoria L. Stevens, Hallie Carol, Matthew L. Freedman, Mark M. Pomerantz, Eunyoung Cho, Peter Kraft, Mark A. Preston, Kathryn M. Wilson, J. Michael Gaziano, Howard S. Sesso, Amanda Black, Neal D. Freedman, Wen Yi Huang, John G. Anema, Richard J. Kahnoski, Brian R. Lane, Sabrina L. Noyes, David Petillo, Leandro M. Colli, Joshua N. Sampson, Celine Besse, Helene Blanche, Anne Boland, Laurie Burdette, Egor Prokhortchouk, Konstantin G. Skryabin, Meredith Yeager, Mirjana Mijuskovic, Miodrag Ognjanovic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Neonila Szeszenia-Dabrowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, H. Bas Bueno-de-Mesquita, Federico Canzian, Eric J. Duell, Börje Ljungberg, Raviprakash T. Sitaram, Ulrike Peters, Emily White, Garnet L. Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I. Min Lee, Wong Ho Chow, Lee E. Moore, Christopher Wood, Timothy Eisen, James Larkin, Toni K. Choueiri, G. Mark Lathrop, Bin Tean Teh, Jean Francois Deleuze, Xifeng Wu, Richard S. Houlston, Paul Brennan, Stephen J. Chanock, Ghislaine Scelo, Mark P. Purdue

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Abstract

Background Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. Objective We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. Design, setting, and participants Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. Outcome measurements and statistical analysis Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. Results and limitations Longer genetically inferred telomere length was associated with an increased risk of RCC (OR = 2.07 per predicted kilobase increase, 95% confidence interval [CI]: = 1.70–2.53, p < 0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R² > 0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR = 1.73, 95% CI = 1.36–2.21, p < 0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N = 5573, OR = 1.93, 95% CI = 1.50–2.49, p < 0.0001), papillary (N = 573, OR = 1.96, 95% CI = 1.01–3.81, p = 0.046), and chromophobe RCC (N = 203, OR = 2.37, 95% CI = 0.78–7.17, p = 0.13). Conclusions Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. Patient summary Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma. This large Mendelian randomization study utilizes a risk score of telomere length associated genetic variants to demonstrate a strong association between longer predicted leukocyte telomere length and increased risk of developing common subtypes of renal cell carcinoma.

Original language	English (US)
Pages (from-to)	747-754
Number of pages	8
Journal	European urology
Volume	72
Issue number	5
DOIs	https://doi.org/10.1016/j.eururo.2017.07.015
State	Published - Nov 2017

Keywords

Genetic variants
Mendelian randomization
Renal cell carcinoma
Risk
Telomere length

ASJC Scopus subject areas

Urology

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10.1016/j.eururo.2017.07.015

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Machiela, M. J., Hofmann, J. N., Carreras-Torres, R., Brown, K. M., Johansson, M., Wang, Z., Foll, M., Li, P., Rothman, N., Savage, S. A., Gaborieau, V., McKay, J. D., Ye, Y., Henrion, M., Bruinsma, F., Jordan, S., Severi, G., Hveem, K., Vatten, L. J., ... Purdue, M. P. (2017). Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma. European urology, 72(5), 747-754. https://doi.org/10.1016/j.eururo.2017.07.015

Machiela, MJ, Hofmann, JN, Carreras-Torres, R, Brown, KM, Johansson, M, Wang, Z, Foll, M, Li, P, Rothman, N, Savage, SA, Gaborieau, V, McKay, JD, Ye, Y, Henrion, M, Bruinsma, F, Jordan, S, Severi, G, Hveem, K, Vatten, LJ, Fletcher, T, Koppova, K, Larsson, SC, Wolk, A, Banks, RE, Selby, PJ, Easton, DF, Pharoah, P, Andreotti, G, Freeman, LEB, Koutros, S, Albanes, D, Mannisto, S, Weinstein, S, Clark, PE, Edwards, TE, Lipworth, L, Gapstur, SM, Stevens, VL, Carol, H, Freedman, ML, Pomerantz, MM, Cho, E, Kraft, P, Preston, MA, Wilson, KM, Gaziano, JM, Sesso, HS, Black, A, Freedman, ND, Huang, WY, Anema, JG, Kahnoski, RJ, Lane, BR, Noyes, SL, Petillo, D, Colli, LM, Sampson, JN, Besse, C, Blanche, H, Boland, A, Burdette, L, Prokhortchouk, E, Skryabin, KG, Yeager, M, Mijuskovic, M, Ognjanovic, M, Foretova, L, Holcatova, I, Janout, V, Mates, D, Mukeriya, A, Rascu, S, Zaridze, D, Bencko, V, Cybulski, C, Fabianova, E, Jinga, V, Lissowska, J, Lubinski, J, Navratilova, M, Rudnai, P, Szeszenia-Dabrowska, N, Benhamou, S, Cancel-Tassin, G, Cussenot, O, Bueno-de-Mesquita, HB, Canzian, F, Duell, EJ, Ljungberg, B, Sitaram, RT, Peters, U, White, E, Anderson, GL, Johnson, L, Luo, J, Buring, J, Lee, IM, Chow, WH, Moore, LE, Wood, C, Eisen, T, Larkin, J, Choueiri, TK, Lathrop, GM, Teh, BT, Deleuze, JF, Wu, X, Houlston, RS, Brennan, P, Chanock, SJ, Scelo, G & Purdue, MP 2017, 'Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma', European urology, vol. 72, no. 5, pp. 747-754. https://doi.org/10.1016/j.eururo.2017.07.015

@article{1eaf47d799494929afa73bb686bdf8c6,

title = "Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma",

abstract = "Background Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. Objective We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. Design, setting, and participants Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. Outcome measurements and statistical analysis Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. Results and limitations Longer genetically inferred telomere length was associated with an increased risk of RCC (OR = 2.07 per predicted kilobase increase, 95% confidence interval [CI]: = 1.70–2.53, p < 0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2 > 0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR = 1.73, 95% CI = 1.36–2.21, p < 0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N = 5573, OR = 1.93, 95% CI = 1.50–2.49, p < 0.0001), papillary (N = 573, OR = 1.96, 95% CI = 1.01–3.81, p = 0.046), and chromophobe RCC (N = 203, OR = 2.37, 95% CI = 0.78–7.17, p = 0.13). Conclusions Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. Patient summary Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma. This large Mendelian randomization study utilizes a risk score of telomere length associated genetic variants to demonstrate a strong association between longer predicted leukocyte telomere length and increased risk of developing common subtypes of renal cell carcinoma.",

keywords = "Genetic variants, Mendelian randomization, Renal cell carcinoma, Risk, Telomere length",

author = "Machiela, {Mitchell J.} and Hofmann, {Jonathan N.} and Robert Carreras-Torres and Brown, {Kevin M.} and Mattias Johansson and Zhaoming Wang and Matthieu Foll and Peng Li and Nathaniel Rothman and Savage, {Sharon A.} and Valerie Gaborieau and McKay, {James D.} and Yuanqing Ye and Marc Henrion and Fiona Bruinsma and Susan Jordan and Gianluca Severi and Kristian Hveem and Vatten, {Lars J.} and Tony Fletcher and Kvetoslava Koppova and Larsson, {Susanna C.} and Alicja Wolk and Banks, {Rosamonde E.} and Selby, {Peter J.} and Easton, {Douglas F.} and Paul Pharoah and Gabriella Andreotti and Freeman, {Laura E.Beane} and Stella Koutros and Demetrius Albanes and Satu Mannisto and Stephanie Weinstein and Clark, {Peter E.} and Edwards, {Todd E.} and Loren Lipworth and Gapstur, {Susan M.} and Stevens, {Victoria L.} and Hallie Carol and Freedman, {Matthew L.} and Pomerantz, {Mark M.} and Eunyoung Cho and Peter Kraft and Preston, {Mark A.} and Wilson, {Kathryn M.} and Gaziano, {J. Michael} and Sesso, {Howard S.} and Amanda Black and Freedman, {Neal D.} and Huang, {Wen Yi} and Anema, {John G.} and Kahnoski, {Richard J.} and Lane, {Brian R.} and Noyes, {Sabrina L.} and David Petillo and Colli, {Leandro M.} and Sampson, {Joshua N.} and Celine Besse and Helene Blanche and Anne Boland and Laurie Burdette and Egor Prokhortchouk and Skryabin, {Konstantin G.} and Meredith Yeager and Mirjana Mijuskovic and Miodrag Ognjanovic and Lenka Foretova and Ivana Holcatova and Vladimir Janout and Dana Mates and Anush Mukeriya and Stefan Rascu and David Zaridze and Vladimir Bencko and Cezary Cybulski and Eleonora Fabianova and Viorel Jinga and Jolanta Lissowska and Jan Lubinski and Marie Navratilova and Peter Rudnai and Neonila Szeszenia-Dabrowska and Simone Benhamou and Geraldine Cancel-Tassin and Olivier Cussenot and Bueno-de-Mesquita, {H. Bas} and Federico Canzian and Duell, {Eric J.} and B{\"o}rje Ljungberg and Sitaram, {Raviprakash T.} and Ulrike Peters and Emily White and Anderson, {Garnet L.} and Lisa Johnson and Juhua Luo and Julie Buring and Lee, {I. Min} and Chow, {Wong Ho} and Moore, {Lee E.} and Christopher Wood and Timothy Eisen and James Larkin and Choueiri, {Toni K.} and Lathrop, {G. Mark} and Teh, {Bin Tean} and Deleuze, {Jean Francois} and Xifeng Wu and Houlston, {Richard S.} and Paul Brennan and Chanock, {Stephen J.} and Ghislaine Scelo and Purdue, {Mark P.}",

note = "Publisher Copyright: {\textcopyright} 2017",

year = "2017",

month = nov,

doi = "10.1016/j.eururo.2017.07.015",

language = "English (US)",

volume = "72",

pages = "747--754",

journal = "European urology",

issn = "0302-2838",

publisher = "Elsevier",

number = "5",

}

TY - JOUR

T1 - Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma

AU - Machiela, Mitchell J.

AU - Hofmann, Jonathan N.

AU - Carreras-Torres, Robert

AU - Brown, Kevin M.

AU - Johansson, Mattias

AU - Wang, Zhaoming

AU - Foll, Matthieu

AU - Li, Peng

AU - Rothman, Nathaniel

AU - Savage, Sharon A.

AU - Gaborieau, Valerie

AU - McKay, James D.

AU - Ye, Yuanqing

AU - Henrion, Marc

AU - Bruinsma, Fiona

AU - Jordan, Susan

AU - Severi, Gianluca

AU - Hveem, Kristian

AU - Vatten, Lars J.

AU - Fletcher, Tony

AU - Koppova, Kvetoslava

AU - Larsson, Susanna C.

AU - Wolk, Alicja

AU - Banks, Rosamonde E.

AU - Selby, Peter J.

AU - Easton, Douglas F.

AU - Pharoah, Paul

AU - Andreotti, Gabriella

AU - Freeman, Laura E.Beane

AU - Koutros, Stella

AU - Albanes, Demetrius

AU - Mannisto, Satu

AU - Weinstein, Stephanie

AU - Clark, Peter E.

AU - Edwards, Todd E.

AU - Lipworth, Loren

AU - Gapstur, Susan M.

AU - Stevens, Victoria L.

AU - Carol, Hallie

AU - Freedman, Matthew L.

AU - Pomerantz, Mark M.

AU - Cho, Eunyoung

AU - Kraft, Peter

AU - Preston, Mark A.

AU - Wilson, Kathryn M.

AU - Gaziano, J. Michael

AU - Sesso, Howard S.

AU - Black, Amanda

AU - Freedman, Neal D.

AU - Huang, Wen Yi

AU - Anema, John G.

AU - Kahnoski, Richard J.

AU - Lane, Brian R.

AU - Noyes, Sabrina L.

AU - Petillo, David

AU - Colli, Leandro M.

AU - Sampson, Joshua N.

AU - Besse, Celine

AU - Blanche, Helene

AU - Boland, Anne

AU - Burdette, Laurie

AU - Prokhortchouk, Egor

AU - Skryabin, Konstantin G.

AU - Yeager, Meredith

AU - Mijuskovic, Mirjana

AU - Ognjanovic, Miodrag

AU - Foretova, Lenka

AU - Holcatova, Ivana

AU - Janout, Vladimir

AU - Mates, Dana

AU - Mukeriya, Anush

AU - Rascu, Stefan

AU - Zaridze, David

AU - Bencko, Vladimir

AU - Cybulski, Cezary

AU - Fabianova, Eleonora

AU - Jinga, Viorel

AU - Lissowska, Jolanta

AU - Lubinski, Jan

AU - Navratilova, Marie

AU - Rudnai, Peter

AU - Szeszenia-Dabrowska, Neonila

AU - Benhamou, Simone

AU - Cancel-Tassin, Geraldine

AU - Cussenot, Olivier

AU - Bueno-de-Mesquita, H. Bas

AU - Canzian, Federico

AU - Duell, Eric J.

AU - Ljungberg, Börje

AU - Sitaram, Raviprakash T.

AU - Peters, Ulrike

AU - White, Emily

AU - Anderson, Garnet L.

AU - Johnson, Lisa

AU - Luo, Juhua

AU - Buring, Julie

AU - Lee, I. Min

AU - Chow, Wong Ho

AU - Moore, Lee E.

AU - Wood, Christopher

AU - Eisen, Timothy

AU - Larkin, James

AU - Choueiri, Toni K.

AU - Lathrop, G. Mark

AU - Teh, Bin Tean

AU - Deleuze, Jean Francois

AU - Wu, Xifeng

AU - Houlston, Richard S.

AU - Brennan, Paul

AU - Chanock, Stephen J.

AU - Scelo, Ghislaine

AU - Purdue, Mark P.

PY - 2017/11

Y1 - 2017/11

N2 - Background Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. Objective We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. Design, setting, and participants Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. Outcome measurements and statistical analysis Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. Results and limitations Longer genetically inferred telomere length was associated with an increased risk of RCC (OR = 2.07 per predicted kilobase increase, 95% confidence interval [CI]: = 1.70–2.53, p < 0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2 > 0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR = 1.73, 95% CI = 1.36–2.21, p < 0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N = 5573, OR = 1.93, 95% CI = 1.50–2.49, p < 0.0001), papillary (N = 573, OR = 1.96, 95% CI = 1.01–3.81, p = 0.046), and chromophobe RCC (N = 203, OR = 2.37, 95% CI = 0.78–7.17, p = 0.13). Conclusions Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. Patient summary Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma. This large Mendelian randomization study utilizes a risk score of telomere length associated genetic variants to demonstrate a strong association between longer predicted leukocyte telomere length and increased risk of developing common subtypes of renal cell carcinoma.

AB - Background Relative telomere length in peripheral blood leukocytes has been evaluated as a potential biomarker for renal cell carcinoma (RCC) risk in several studies, with conflicting findings. Objective We performed an analysis of genetic variants associated with leukocyte telomere length to assess the relationship between telomere length and RCC risk using Mendelian randomization, an approach unaffected by biases from temporal variability and reverse causation that might have affected earlier investigations. Design, setting, and participants Genotypes from nine telomere length-associated variants for 10 784 cases and 20 406 cancer-free controls from six genome-wide association studies (GWAS) of RCC were aggregated into a weighted genetic risk score (GRS) predictive of leukocyte telomere length. Outcome measurements and statistical analysis Odds ratios (ORs) relating the GRS and RCC risk were computed in individual GWAS datasets and combined by meta-analysis. Results and limitations Longer genetically inferred telomere length was associated with an increased risk of RCC (OR = 2.07 per predicted kilobase increase, 95% confidence interval [CI]: = 1.70–2.53, p < 0.0001). As a sensitivity analysis, we excluded two telomere length variants in linkage disequilibrium (R2 > 0.5) with GWAS-identified RCC risk variants (rs10936599 and rs9420907) from the telomere length GRS; despite this exclusion, a statistically significant association between the GRS and RCC risk persisted (OR = 1.73, 95% CI = 1.36–2.21, p < 0.0001). Exploratory analyses for individual histologic subtypes suggested comparable associations with the telomere length GRS for clear cell (N = 5573, OR = 1.93, 95% CI = 1.50–2.49, p < 0.0001), papillary (N = 573, OR = 1.96, 95% CI = 1.01–3.81, p = 0.046), and chromophobe RCC (N = 203, OR = 2.37, 95% CI = 0.78–7.17, p = 0.13). Conclusions Our investigation adds to the growing body of evidence indicating some aspect of longer telomere length is important for RCC risk. Patient summary Telomeres are segments of DNA at chromosome ends that maintain chromosomal stability. Our study investigated the relationship between genetic variants associated with telomere length and renal cell carcinoma risk. We found evidence suggesting individuals with inherited predisposition to longer telomere length are at increased risk of developing renal cell carcinoma. This large Mendelian randomization study utilizes a risk score of telomere length associated genetic variants to demonstrate a strong association between longer predicted leukocyte telomere length and increased risk of developing common subtypes of renal cell carcinoma.

KW - Genetic variants

KW - Mendelian randomization

KW - Renal cell carcinoma

KW - Risk

KW - Telomere length

UR - http://www.scopus.com/inward/record.url?scp=85026873779&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85026873779&partnerID=8YFLogxK

U2 - 10.1016/j.eururo.2017.07.015

DO - 10.1016/j.eururo.2017.07.015

M3 - Article

C2 - 28797570

AN - SCOPUS:85026873779

SN - 0302-2838

VL - 72

SP - 747

EP - 754

JO - European urology

JF - European urology

IS - 5

ER -

Genetic Variants Related to Longer Telomere Length are Associated with Increased Risk of Renal Cell Carcinoma

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