Elevated platelet count appears to be causally associated with increased risk of lung cancer: A mendelian randomization analysis

Ying Zhu; Yongyue Wei; Ruyang Zhang; Xuesi Dong; Sipeng Shen; Yang Zhao; Jianling Bai; Demetrius Albanes; Neil E. Caporaso; Maria Teresa Landi; Bin Zhu; Stephen J. Chanock; Fangyi Gu; Stephen Lam; Ming Sound Tsao; Frances A. Shepherd; Adonina Tardon; Ana Fernandez-Somoano; Guillermo Fernandez-Tardon; Chu Chen; Matthew J. Barnett; Jennifer Doherty; Stig E. Bojesen; Mattias Johansson; Paul Brennan; James D. McKay; Robert Carreras-Torres; Thomas Muley; Angela Risch; Heunz Erich Wichmann; Heike Bickeboeller; Albert Rosenberger; Gad Rennert; Walid Saliba; Susanne M. Arnold; John K. Field; Michael P.A. Davies; Michael W. Marcus; Xifeng Wu; Yuanqing Ye; Loic Le Marchand; Lynne R. Wilkens; Olle Melander; Jonas Manjer; Hans Brunnstrom; Rayjean J. Hung; Geoffrey Liu; Yonathan Brhane; Linda Kachuri; Angeline S. Andrew; Eric J. Duell; Lambertus A. Kiemeney; Erik H.F.M. Van der Heijden; Aage Haugen; Shanbeh Zienolddiny; Vidar Skaug; Kjell Grankvist; Mikael Johansson; Penella J. Woll; Angela Cox; Fiona Taylor; Dawn M. Teare; Philip Lazarus; Matthew B. Schabath; Melinda C. Aldrich; Richard S. Houlston; John McLaughlin; Victoria L. Stevens; Hongbing Shen; Zhibin Hu; Juncheng Dai; Christopher I. Amos; Younghun Han; Dakai Zhu; Gary E. Goodman; Feng Chen; David C. Christiani

doi:10.1158/1055-9965.epi-18-0356

Elevated platelet count appears to be causally associated with increased risk of lung cancer: A mendelian randomization analysis

Ying Zhu, Yongyue Wei, Ruyang Zhang, Xuesi Dong, Sipeng Shen, Yang Zhao, Jianling Bai, Demetrius Albanes, Neil E. Caporaso, Maria Teresa Landi, Bin Zhu, Stephen J. Chanock, Fangyi Gu, Stephen Lam, Ming Sound Tsao, Frances A. Shepherd, Adonina Tardon, Ana Fernandez-Somoano, Guillermo Fernandez-Tardon, Chu ChenMatthew J. Barnett, Jennifer Doherty, Stig E. Bojesen, Mattias Johansson, Paul Brennan, James D. McKay, Robert Carreras-Torres, Thomas Muley, Angela Risch, Heunz Erich Wichmann, Heike Bickeboeller, Albert Rosenberger, Gad Rennert, Walid Saliba, Susanne M. Arnold, John K. Field, Michael P.A. Davies, Michael W. Marcus, Xifeng Wu, Yuanqing Ye, Loic Le Marchand, Lynne R. Wilkens, Olle Melander, Jonas Manjer, Hans Brunnstrom, Rayjean J. Hung, Geoffrey Liu, Yonathan Brhane, Linda Kachuri, Angeline S. Andrew, Eric J. Duell, Lambertus A. Kiemeney, Erik H.F.M. Van der Heijden, Aage Haugen, Shanbeh Zienolddiny, Vidar Skaug, Kjell Grankvist, Mikael Johansson, Penella J. Woll, Angela Cox, Fiona Taylor, Dawn M. Teare, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Richard S. Houlston, John McLaughlin, Victoria L. Stevens, Hongbing Shen, Zhibin Hu, Juncheng Dai, Christopher I. Amos, Younghun Han, Dakai Zhu, Gary E. Goodman, Feng Chen^*, David C. Christiani

^*Corresponding author af dette arbejde

Institut for Klinisk Medicin

11 Citationer (Scopus)

Abstract

Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non–small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15–2.27; P ¼ 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27–7.06; P ¼ 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

Originalsprog	Engelsk
Tidsskrift	Cancer Epidemiology Biomarkers and Prevention
Vol/bind	28
Udgave nummer	5
Sider (fra-til)	935-942
Antal sider	8
ISSN	1055-9965
DOI	https://doi.org/10.1158/1055-9965.epi-18-0356
Status	Udgivet - 2019

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10.1158/1055-9965.epi-18-0356

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Zhu, Y., Wei, Y., Zhang, R., Dong, X., Shen, S., Zhao, Y., Bai, J., Albanes, D., Caporaso, N. E., Landi, M. T., Zhu, B., Chanock, S. J., Gu, F., Lam, S., Tsao, M. S., Shepherd, F. A., Tardon, A., Fernandez-Somoano, A., Fernandez-Tardon, G., ... Christiani, D. C. (2019). Elevated platelet count appears to be causally associated with increased risk of lung cancer: A mendelian randomization analysis. Cancer Epidemiology Biomarkers and Prevention, 28(5), 935-942. https://doi.org/10.1158/1055-9965.epi-18-0356

Zhu, Y, Wei, Y, Zhang, R, Dong, X, Shen, S, Zhao, Y, Bai, J, Albanes, D, Caporaso, NE, Landi, MT, Zhu, B, Chanock, SJ, Gu, F, Lam, S, Tsao, MS, Shepherd, FA, Tardon, A, Fernandez-Somoano, A, Fernandez-Tardon, G, Chen, C, Barnett, MJ, Doherty, J, Bojesen, SE, Johansson, M, Brennan, P, McKay, JD, Carreras-Torres, R, Muley, T, Risch, A, Wichmann, HE, Bickeboeller, H, Rosenberger, A, Rennert, G, Saliba, W, Arnold, SM, Field, JK, Davies, MPA, Marcus, MW, Wu, X, Ye, Y, Le Marchand, L, Wilkens, LR, Melander, O, Manjer, J, Brunnstrom, H, Hung, RJ, Liu, G, Brhane, Y, Kachuri, L, Andrew, AS, Duell, EJ, Kiemeney, LA, Van der Heijden, EHFM, Haugen, A, Zienolddiny, S, Skaug, V, Grankvist, K, Johansson, M, Woll, PJ, Cox, A, Taylor, F, Teare, DM, Lazarus, P, Schabath, MB, Aldrich, MC, Houlston, RS, McLaughlin, J, Stevens, VL, Shen, H, Hu, Z, Dai, J, Amos, CI, Han, Y, Zhu, D, Goodman, GE, Chen, F & Christiani, DC 2019, 'Elevated platelet count appears to be causally associated with increased risk of lung cancer: A mendelian randomization analysis', Cancer Epidemiology Biomarkers and Prevention, bind 28, nr. 5, s. 935-942. https://doi.org/10.1158/1055-9965.epi-18-0356

@article{9d6b4e35f3f344c7806f0c7838186101,

title = "Elevated platelet count appears to be causally associated with increased risk of lung cancer: A mendelian randomization analysis",

abstract = "Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non–small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15–2.27; P ¼ 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27–7.06; P ¼ 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.",

author = "Ying Zhu and Yongyue Wei and Ruyang Zhang and Xuesi Dong and Sipeng Shen and Yang Zhao and Jianling Bai and Demetrius Albanes and Caporaso, {Neil E.} and Landi, {Maria Teresa} and Bin Zhu and Chanock, {Stephen J.} and Fangyi Gu and Stephen Lam and Tsao, {Ming Sound} and Shepherd, {Frances A.} and Adonina Tardon and Ana Fernandez-Somoano and Guillermo Fernandez-Tardon and Chu Chen and Barnett, {Matthew J.} and Jennifer Doherty and Bojesen, {Stig E.} and Mattias Johansson and Paul Brennan and McKay, {James D.} and Robert Carreras-Torres and Thomas Muley and Angela Risch and Wichmann, {Heunz Erich} and Heike Bickeboeller and Albert Rosenberger and Gad Rennert and Walid Saliba and Arnold, {Susanne M.} and Field, {John K.} and Davies, {Michael P.A.} and Marcus, {Michael W.} and Xifeng Wu and Yuanqing Ye and {Le Marchand}, Loic and Wilkens, {Lynne R.} and Olle Melander and Jonas Manjer and Hans Brunnstrom and Hung, {Rayjean J.} and Geoffrey Liu and Yonathan Brhane and Linda Kachuri and Andrew, {Angeline S.} and Duell, {Eric J.} and Kiemeney, {Lambertus A.} and {Van der Heijden}, {Erik H.F.M.} and Aage Haugen and Shanbeh Zienolddiny and Vidar Skaug and Kjell Grankvist and Mikael Johansson and Woll, {Penella J.} and Angela Cox and Fiona Taylor and Teare, {Dawn M.} and Philip Lazarus and Schabath, {Matthew B.} and Aldrich, {Melinda C.} and Houlston, {Richard S.} and John McLaughlin and Stevens, {Victoria L.} and Hongbing Shen and Zhibin Hu and Juncheng Dai and Amos, {Christopher I.} and Younghun Han and Dakai Zhu and Goodman, {Gary E.} and Feng Chen and Christiani, {David C.}",

year = "2019",

doi = "10.1158/1055-9965.epi-18-0356",

language = "English",

volume = "28",

pages = "935--942",

journal = "Cancer Epidemiology, Biomarkers & Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research (A A C R)",

number = "5",

}

TY - JOUR

T1 - Elevated platelet count appears to be causally associated with increased risk of lung cancer

T2 - A mendelian randomization analysis

AU - Zhu, Ying

AU - Wei, Yongyue

AU - Zhang, Ruyang

AU - Dong, Xuesi

AU - Shen, Sipeng

AU - Zhao, Yang

AU - Bai, Jianling

AU - Albanes, Demetrius

AU - Caporaso, Neil E.

AU - Landi, Maria Teresa

AU - Zhu, Bin

AU - Chanock, Stephen J.

AU - Gu, Fangyi

AU - Lam, Stephen

AU - Tsao, Ming Sound

AU - Shepherd, Frances A.

AU - Tardon, Adonina

AU - Fernandez-Somoano, Ana

AU - Fernandez-Tardon, Guillermo

AU - Chen, Chu

AU - Barnett, Matthew J.

AU - Doherty, Jennifer

AU - Bojesen, Stig E.

AU - Johansson, Mattias

AU - Brennan, Paul

AU - McKay, James D.

AU - Carreras-Torres, Robert

AU - Muley, Thomas

AU - Risch, Angela

AU - Wichmann, Heunz Erich

AU - Bickeboeller, Heike

AU - Rosenberger, Albert

AU - Rennert, Gad

AU - Saliba, Walid

AU - Arnold, Susanne M.

AU - Field, John K.

AU - Davies, Michael P.A.

AU - Marcus, Michael W.

AU - Wu, Xifeng

AU - Ye, Yuanqing

AU - Le Marchand, Loic

AU - Wilkens, Lynne R.

AU - Melander, Olle

AU - Manjer, Jonas

AU - Brunnstrom, Hans

AU - Hung, Rayjean J.

AU - Liu, Geoffrey

AU - Brhane, Yonathan

AU - Kachuri, Linda

AU - Andrew, Angeline S.

AU - Duell, Eric J.

AU - Kiemeney, Lambertus A.

AU - Van der Heijden, Erik H.F.M.

AU - Haugen, Aage

AU - Zienolddiny, Shanbeh

AU - Skaug, Vidar

AU - Grankvist, Kjell

AU - Johansson, Mikael

AU - Woll, Penella J.

AU - Cox, Angela

AU - Taylor, Fiona

AU - Teare, Dawn M.

AU - Lazarus, Philip

AU - Schabath, Matthew B.

AU - Aldrich, Melinda C.

AU - Houlston, Richard S.

AU - McLaughlin, John

AU - Stevens, Victoria L.

AU - Shen, Hongbing

AU - Hu, Zhibin

AU - Dai, Juncheng

AU - Amos, Christopher I.

AU - Han, Younghun

AU - Zhu, Dakai

AU - Goodman, Gary E.

AU - Chen, Feng

AU - Christiani, David C.

PY - 2019

Y1 - 2019

N2 - Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non–small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15–2.27; P ¼ 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27–7.06; P ¼ 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

AB - Background: Platelets are a critical element in coagulation and inflammation, and activated platelets are linked to cancer risk through diverse mechanisms. However, a causal relationship between platelets and risk of lung cancer remains unclear. Methods: We performed single and combined multiple instrumental variable Mendelian randomization analysis by an inverse-weighted method, in addition to a series of sensitivity analyses. Summary data for associations between SNPs and platelet count are from a recent publication that included 48,666 Caucasian Europeans, and the International Lung Cancer Consortium and Transdisciplinary Research in Cancer of the Lung data consisting of 29,266 cases and 56,450 controls to analyze associations between candidate SNPs and lung cancer risk. Results: Multiple instrumental variable analysis incorporating six SNPs showed a 62% increased risk of overall non–small cell lung cancer [NSCLC; OR, 1.62; 95% confidence interval (CI), 1.15–2.27; P ¼ 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27–7.06; P ¼ 0.01). Results showed only a trending association with NSCLC histologic subtypes, which may be due to insufficient sample size and/or weak effect size. A series of sensitivity analysis retained these findings. Conclusions: Our findings suggest a causal relationship between elevated platelet count and increased risk of lung cancer and provide evidence of possible antiplatelet interventions for lung cancer prevention. Impact: These findings provide a better understanding of lung cancer etiology and potential evidence for antiplatelet interventions for lung cancer prevention.

U2 - 10.1158/1055-9965.epi-18-0356

DO - 10.1158/1055-9965.epi-18-0356

M3 - Journal article

C2 - 30700444

AN - SCOPUS:85065599711

SN - 1055-9965

VL - 28

SP - 935

EP - 942

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

IS - 5

ER -

Elevated platelet count appears to be causally associated with increased risk of lung cancer: A mendelian randomization analysis

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