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Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis

, ; Zhu, Ying; Melander, Olle LU ; Manjer, Jonas LU ; Brunnström, Hans LU and Christiani, David C. (2019) In Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 28(5). p.935-942
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... (More)
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 = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 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. ©2019 American Association for Cancer Research. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
volume
28
issue
5
pages
8 pages
publisher
American Association for Cancer Research
external identifiers
  • scopus:85065599711
ISSN
1538-7755
DOI
10.1158/1055-9965.EPI-18-0356
language
English
LU publication?
yes
id
d77d5117-30e6-4646-a65f-3a1d75c721fa
date added to LUP
2019-05-23 13:10:17
date last changed
2019-05-28 02:21:20
@article{d77d5117-30e6-4646-a65f-3a1d75c721fa,
  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 = 0.005] and a 200% increased risk for small-cell lung cancer (OR, 3.00; 95% CI, 1.27-7.06; P = 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. ©2019 American Association for Cancer Research.},
  author       = {,  and Zhu, Ying and Melander, Olle and Manjer, Jonas and Brunnström, Hans and Christiani, David C.},
  issn         = {1538-7755},
  language     = {eng},
  number       = {5},
  pages        = {935--942},
  publisher    = {American Association for Cancer Research},
  series       = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},
  title        = {Elevated Platelet Count Appears to Be Causally Associated with Increased Risk of Lung Cancer: A Mendelian Randomization Analysis},
  url          = {http://dx.doi.org/10.1158/1055-9965.EPI-18-0356},
  volume       = {28},
  year         = {2019},
}