Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations
Abstract Background The associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian randomization investigation of the associations of RA with site-specific cancers in European and East Asian pop...
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BMC
2022-12-01
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Series: | Arthritis Research & Therapy |
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Online Access: | https://doi.org/10.1186/s13075-022-02970-z |
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author | Shuai Yuan Jie Chen Xixian Ruan Mathew Vithayathil Siddhartha Kar Xue Li Amy M. Mason Stephen Burgess Susanna C. Larsson |
author_facet | Shuai Yuan Jie Chen Xixian Ruan Mathew Vithayathil Siddhartha Kar Xue Li Amy M. Mason Stephen Burgess Susanna C. Larsson |
author_sort | Shuai Yuan |
collection | DOAJ |
description | Abstract Background The associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian randomization investigation of the associations of RA with site-specific cancers in European and East Asian populations. Methods Independent genetic variants strongly associated with RA in European and East Asian populations were selected as instrumental variables from genome-wide association studies of 58,284 European individuals (14,361 cases and 43,923 controls) and 22,515 East Asian individuals (4873 cases and 17,642 controls), respectively. The associations of genetic variants with overall and 22 site-specific cancers were extracted from the UK Biobank study (n = 367,561), the FinnGen study (n = 260,405), Biobank Japan (n = 212,453), and international consortia. The associations for one outcome from different data sources were combined by meta-analysis. Results In the European population, the combined odds ratios per 1-unit increase in log odds of genetic liability to RA were 1.06 (95% confidence interval [CI] 1.03–1.10) for head and neck cancer, 1.06 (95% CI 1.02–1.10) for cervical cancer, 0.92 (95% CI 0.87–0.96) for testicular cancer, and 0.94 (95% CI 0.90–0.98) for multiple myeloma. In the East Asian population, the corresponding odds ratios were 1.17 (95% CI 1.06–1.29) for pancreatic cancer, 0.91 (95% CI 0.88–0.94) for breast cancer, and 0.90 (95% CI 0.84–0.96) for ovarian cancer. There were suggestive associations for breast and ovarian cancer and overall cancer in the European population. No other associations were observed. Conclusion This study suggests that RA may play a role in the development of several site-specific cancers. |
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language | English |
last_indexed | 2024-04-13T04:31:04Z |
publishDate | 2022-12-01 |
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series | Arthritis Research & Therapy |
spelling | doaj.art-267e177637e049949877180d09047e492022-12-22T03:02:18ZengBMCArthritis Research & Therapy1478-63622022-12-012411910.1186/s13075-022-02970-zRheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populationsShuai Yuan0Jie Chen1Xixian Ruan2Mathew Vithayathil3Siddhartha Kar4Xue Li5Amy M. Mason6Stephen Burgess7Susanna C. Larsson8Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska InstitutetCentre for Global Health, Zhejiang University School of MedicineDepartment of Gastroenterology, The Third Xiangya Hospital, Central South UniversityMRC Cancer Unit, University of CambridgeMRC Integrative Epidemiology Unit, Bristol Medical School, University of BristolDepartment of Big Data in Health Science School of Public Health, Center of Clinical Big Data and Analytics of The Second Affiliated Hospital, Zhejiang University School of MedicineBritish Heart Foundation Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of CambridgeMRC Biostatistics Unit, University of CambridgeUnit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska InstitutetAbstract Background The associations of rheumatoid arthritis (RA) with risk of site-specific cancers beyond lymphohematopoietic cancer have been scarcely explored. We conducted a Mendelian randomization investigation of the associations of RA with site-specific cancers in European and East Asian populations. Methods Independent genetic variants strongly associated with RA in European and East Asian populations were selected as instrumental variables from genome-wide association studies of 58,284 European individuals (14,361 cases and 43,923 controls) and 22,515 East Asian individuals (4873 cases and 17,642 controls), respectively. The associations of genetic variants with overall and 22 site-specific cancers were extracted from the UK Biobank study (n = 367,561), the FinnGen study (n = 260,405), Biobank Japan (n = 212,453), and international consortia. The associations for one outcome from different data sources were combined by meta-analysis. Results In the European population, the combined odds ratios per 1-unit increase in log odds of genetic liability to RA were 1.06 (95% confidence interval [CI] 1.03–1.10) for head and neck cancer, 1.06 (95% CI 1.02–1.10) for cervical cancer, 0.92 (95% CI 0.87–0.96) for testicular cancer, and 0.94 (95% CI 0.90–0.98) for multiple myeloma. In the East Asian population, the corresponding odds ratios were 1.17 (95% CI 1.06–1.29) for pancreatic cancer, 0.91 (95% CI 0.88–0.94) for breast cancer, and 0.90 (95% CI 0.84–0.96) for ovarian cancer. There were suggestive associations for breast and ovarian cancer and overall cancer in the European population. No other associations were observed. Conclusion This study suggests that RA may play a role in the development of several site-specific cancers.https://doi.org/10.1186/s13075-022-02970-zEast AsianEuropeanMendelian randomizationRheumatoid arthritis |
spellingShingle | Shuai Yuan Jie Chen Xixian Ruan Mathew Vithayathil Siddhartha Kar Xue Li Amy M. Mason Stephen Burgess Susanna C. Larsson Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations Arthritis Research & Therapy East Asian European Mendelian randomization Rheumatoid arthritis |
title | Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations |
title_full | Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations |
title_fullStr | Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations |
title_full_unstemmed | Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations |
title_short | Rheumatoid arthritis and risk of site-specific cancers: Mendelian randomization study in European and East Asian populations |
title_sort | rheumatoid arthritis and risk of site specific cancers mendelian randomization study in european and east asian populations |
topic | East Asian European Mendelian randomization Rheumatoid arthritis |
url | https://doi.org/10.1186/s13075-022-02970-z |
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