Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study
Linshuoshuo Lv,1,* Xiaohui Sun,1,* Bin Liu,1 Jie Song,1 David JH Wu,2 Yun Gao,3 Aole Li,3 Xiaoqin Hu,4 Yingying Mao,1 Ding Ye1 1Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2University of Minne...
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| Format: | Article |
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Dove Medical Press
2022-06-01
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| Series: | Clinical Epidemiology |
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| Online Access: | https://www.dovepress.com/genetically-predicted-serum-albumin-and-risk-of-colorectal-cancer-a-bi-peer-reviewed-fulltext-article-CLEP |
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| author | Lv L Sun X Liu B Song J Wu DJH Gao Y Li A Hu X Mao Y Ye D |
| author_facet | Lv L Sun X Liu B Song J Wu DJH Gao Y Li A Hu X Mao Y Ye D |
| author_sort | Lv L |
| collection | DOAJ |
| description | Linshuoshuo Lv,1,* Xiaohui Sun,1,* Bin Liu,1 Jie Song,1 David JH Wu,2 Yun Gao,3 Aole Li,3 Xiaoqin Hu,4 Yingying Mao,1 Ding Ye1 1Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2University of Minnesota Medical School, Minneapolis, MN, 55455, USA; 3Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ding Ye; Yingying Mao, Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Zhejiang, Hangzhou, 310053, People’s Republic of China, Tel +86-571-8663-3305, Email yeding@zcmu.edu.cn; myy@zcmu.edu.cnPurpose: Colorectal cancer (CRC) is the third–most frequently diagnosed cancer globally. Studies have linked low serum albumin with increased risk of CRC, but the causal nature of the association remains unclear. In the present study, we explored the potential causal relationship using bidirectional Mendelian randomization (MR).Methods: Instrumental variants for albumin were obtained from a genome-wide association study (GWAS) on 102,223 Eastern Asian participants to investigate the effect of albumin on CRC. Summary statistics of CRC were obtained from a GWAS on 7,062 CRC cases and 195,745 controls of Eastern Asian ancestry. Bidirectional MR analysis was performed using inverse variance weighting (IVW) for primary analysis, supplemented with a maximum likelihood–based method, MR-PRESSO test, leave-one-out analysis, and MR-Egger regression. Stratification analyses were further performed.Results: We found that genetically predicted serum albumin per unit was associated with a lower risk of CRC (OR 0.75, 95% CI 0.59– 0.95 with IVW). No evidence of pleiotropy was observed. Sex-stratified MR analysis showed that serum albumin was inversely associated with risk of CRC in men (OR 0.71, 95% CI 0.53– 0.96), but not in women (OR 0.81, 95% CI 0.55– 1.19) using IVW. Reverse MR analysis suggested a genetic predisposition toward CRC was not associated with serum albumin.Conclusion: Our study revealed a suggestive sex disparity in the effect of albumin, which deserves further exploration of the potential biological mechanism.Keywords: albumin, colorectal cancer, Mendelian randomization, single-nucleotide polymorphism, genome-wide association study, instrumental variables |
| first_indexed | 2024-04-12T13:27:38Z |
| format | Article |
| id | doaj.art-c44bb6e03f75435eaeaf346d15a49b5e |
| institution | Directory Open Access Journal |
| issn | 1179-1349 |
| language | English |
| last_indexed | 2024-04-12T13:27:38Z |
| publishDate | 2022-06-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Clinical Epidemiology |
| spelling | doaj.art-c44bb6e03f75435eaeaf346d15a49b5e2022-12-22T03:31:16ZengDove Medical PressClinical Epidemiology1179-13492022-06-01Volume 1477177876098Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization StudyLv LSun XLiu BSong JWu DJHGao YLi AHu XMao YYe DLinshuoshuo Lv,1,* Xiaohui Sun,1,* Bin Liu,1 Jie Song,1 David JH Wu,2 Yun Gao,3 Aole Li,3 Xiaoqin Hu,4 Yingying Mao,1 Ding Ye1 1Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2University of Minnesota Medical School, Minneapolis, MN, 55455, USA; 3Fourth School of Clinical Medicine, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Ding Ye; Yingying Mao, Department of Epidemiology, School of Public Health, Zhejiang Chinese Medical University, 548 Binwen Road, Zhejiang, Hangzhou, 310053, People’s Republic of China, Tel +86-571-8663-3305, Email yeding@zcmu.edu.cn; myy@zcmu.edu.cnPurpose: Colorectal cancer (CRC) is the third–most frequently diagnosed cancer globally. Studies have linked low serum albumin with increased risk of CRC, but the causal nature of the association remains unclear. In the present study, we explored the potential causal relationship using bidirectional Mendelian randomization (MR).Methods: Instrumental variants for albumin were obtained from a genome-wide association study (GWAS) on 102,223 Eastern Asian participants to investigate the effect of albumin on CRC. Summary statistics of CRC were obtained from a GWAS on 7,062 CRC cases and 195,745 controls of Eastern Asian ancestry. Bidirectional MR analysis was performed using inverse variance weighting (IVW) for primary analysis, supplemented with a maximum likelihood–based method, MR-PRESSO test, leave-one-out analysis, and MR-Egger regression. Stratification analyses were further performed.Results: We found that genetically predicted serum albumin per unit was associated with a lower risk of CRC (OR 0.75, 95% CI 0.59– 0.95 with IVW). No evidence of pleiotropy was observed. Sex-stratified MR analysis showed that serum albumin was inversely associated with risk of CRC in men (OR 0.71, 95% CI 0.53– 0.96), but not in women (OR 0.81, 95% CI 0.55– 1.19) using IVW. Reverse MR analysis suggested a genetic predisposition toward CRC was not associated with serum albumin.Conclusion: Our study revealed a suggestive sex disparity in the effect of albumin, which deserves further exploration of the potential biological mechanism.Keywords: albumin, colorectal cancer, Mendelian randomization, single-nucleotide polymorphism, genome-wide association study, instrumental variableshttps://www.dovepress.com/genetically-predicted-serum-albumin-and-risk-of-colorectal-cancer-a-bi-peer-reviewed-fulltext-article-CLEPalbumincolorectal cancermendelian randomizationsingle-nucleotide polymorphismgenome-wide association studyinstrumental variables. |
| spellingShingle | Lv L Sun X Liu B Song J Wu DJH Gao Y Li A Hu X Mao Y Ye D Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study Clinical Epidemiology albumin colorectal cancer mendelian randomization single-nucleotide polymorphism genome-wide association study instrumental variables. |
| title | Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study |
| title_full | Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study |
| title_fullStr | Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study |
| title_full_unstemmed | Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study |
| title_short | Genetically Predicted Serum Albumin and Risk of Colorectal Cancer: A Bidirectional Mendelian Randomization Study |
| title_sort | genetically predicted serum albumin and risk of colorectal cancer a bidirectional mendelian randomization study |
| topic | albumin colorectal cancer mendelian randomization single-nucleotide polymorphism genome-wide association study instrumental variables. |
| url | https://www.dovepress.com/genetically-predicted-serum-albumin-and-risk-of-colorectal-cancer-a-bi-peer-reviewed-fulltext-article-CLEP |
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