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

VL - 28

SP - 935

EP - 942

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 5

ER -