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Cancer Innovation 2022, 1(4): 316-327 https://doi.org/10.1002/cai2.36
Original Article | Open Access | Issue | Published: 07 December 2022

Causal relationship between 14 site‐specific cancers and venous thromboembolism

Show Author's Information Xiong Chen1,2,  Xiaosi Hong3,  Shulu Luo4,  Jiahao Cai5,  Guiwu Huang6,  Runnan Shen7,  Lin Lv7,  Gaochen Bai1,2,  Wen Fu1,2,  Li Yan3,  Guochang Liu1,2( ),  Kai Huang8( ),  Qinchang Chen9( )
Department of Paediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Department of Paediatric Surgery, Guangzhou Institute of Paediatrics, Guangzhou Medical University, Guangzhou, China
Department of Endocrinology, Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University, Guangzhou, China
Department of Prosthodontics, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‐sen University, Guangzhou, China
Department of Pediatric Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Department of Orthopedics, The First Affiliated Hospital of Sun Yat‐Sen University, Guangzhou, China
Medical School, Sun Yat‐sen University, Guangzhou, China
Department of Cardiovascular Surgery, Sun Yat‐sen Memorial Hospital, Guangzhou, China
Department of Pediatric Cardiology, Guangdong Provincial Key Laboratory of Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, China
Keywords:
cancer, venous thromboembolism, Mendelian randomization, causal effect
Cite this article:
Chen X, Hong X, Luo S, et al. Causal relationship between 14 site‐specific cancers and venous thromboembolism. Cancer Innovation, 2022, 1(4): 316-327. https://doi.org/10.1002/cai2.36
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Abstract Full text About this article
Background

It has been observed that cancer and venous thromboembolism (VTE) are associated, but anticancer therapy may violate the causality. Therefore, this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization (MR).

Methods

Three MR methods were used to estimate causal effects: Inverse variance weighted (IVW), MR‐Egger and weighted median. Sensitivity analyses included Cochran's Q‐test, MR‐Egger intercept test and MR‐PRESSO. Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients.

Results

The primary IVW approach showed that non‐Hodgkin's lymphoma (NHL) might increase the risk of VTE (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.00–1.44, p = 0.045), while melanoma possibly reduced the risk of VTE (OR: 0.89, 95% CI: 0.82–0.97, p = 0.006), although there was no significance after adjustment for multiple testing. No association was observed between VTE risk and other site‐specific cancers. Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients.

Conclusions

Our findings suggested that genetically predicted NHL was associated with higher VTE risk, whereas melanoma had lower VTE risk compared with other site‐specific cancers. Moreover, this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.


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Abstract
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About this article

Causal relationship between 14 site‐specific cancers and venous thromboembolism

Show Author's information Xiong Chen1,2, Xiaosi Hong3, Shulu Luo4, Jiahao Cai5, Guiwu Huang6, Runnan Shen7, Lin Lv7, Gaochen Bai1,2, Wen Fu1,2, Li Yan3, Guochang Liu1,2( ), Kai Huang8( ), Qinchang Chen9( )
Department of Paediatric Urology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Department of Paediatric Surgery, Guangzhou Institute of Paediatrics, Guangzhou Medical University, Guangzhou, China
Department of Endocrinology, Sun Yat‐sen Memorial Hospital, Sun Yat‐sen University, Guangzhou, China
Department of Prosthodontics, Hospital of Stomatology, Guanghua School of Stomatology, Guangdong Provincial Key Laboratory of Stomatology, Sun Yat‐sen University, Guangzhou, China
Department of Pediatric Neurology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China
Department of Orthopedics, The First Affiliated Hospital of Sun Yat‐Sen University, Guangzhou, China
Medical School, Sun Yat‐sen University, Guangzhou, China
Department of Cardiovascular Surgery, Sun Yat‐sen Memorial Hospital, Guangzhou, China
Department of Pediatric Cardiology, Guangdong Provincial Key Laboratory of Structural Heart Disease, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangdong Cardiovascular Institute, Guangzhou, China

Abstract

Background

It has been observed that cancer and venous thromboembolism (VTE) are associated, but anticancer therapy may violate the causality. Therefore, this study aimed to elucidate the causal relationship of various cancers to VTE using Mendelian randomization (MR).

Methods

Three MR methods were used to estimate causal effects: Inverse variance weighted (IVW), MR‐Egger and weighted median. Sensitivity analyses included Cochran's Q‐test, MR‐Egger intercept test and MR‐PRESSO. Gene ontology enrichment analysis was performed to elucidate the underlying mechanisms of VTE development in cancer patients.

Results

The primary IVW approach showed that non‐Hodgkin's lymphoma (NHL) might increase the risk of VTE (odds ratio [OR]: 1.20, 95% confidence interval [95% CI]: 1.00–1.44, p = 0.045), while melanoma possibly reduced the risk of VTE (OR: 0.89, 95% CI: 0.82–0.97, p = 0.006), although there was no significance after adjustment for multiple testing. No association was observed between VTE risk and other site‐specific cancers. Gene ontology enrichment analysis revealed that vitamin D played an important role in the development of VTE in cancer patients.

Conclusions

Our findings suggested that genetically predicted NHL was associated with higher VTE risk, whereas melanoma had lower VTE risk compared with other site‐specific cancers. Moreover, this study suggested that anticancer therapy and increased extensive examination might play a more important role in VTE development than the nature of cancer.

Keywords: cancer, venous thromboembolism, Mendelian randomization, causal effect

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Publication history
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Publication history

Received: 13 October 2022
Accepted: 30 October 2022
Published: 07 December 2022
Issue date: December 2022

Copyright

© 2022 The Authors.

Acknowledgements

We thank the participants of UK Biobank, FinnGen and GERA consortium.

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This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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