A Mendelian randomization study of type 2 diabetes and cancer risk in East Asians
Abstract Our research aims to explore genetic correlation between T2D predisposition and risks of several cancers, which have been predominantly focused on populations of European ancestry. In an East Asian population, we leverage two-sample Mendelian Randomization to investigate the complex associa...
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BMC
2025-08-01
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| Series: | Cancer Cell International |
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| Online Access: | https://doi.org/10.1186/s12935-025-03929-1 |
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| author | Ling Li Fangxuan Li Zhanyu Pan |
| author_facet | Ling Li Fangxuan Li Zhanyu Pan |
| author_sort | Ling Li |
| collection | DOAJ |
| description | Abstract Our research aims to explore genetic correlation between T2D predisposition and risks of several cancers, which have been predominantly focused on populations of European ancestry. In an East Asian population, we leverage two-sample Mendelian Randomization to investigate the complex association between Type 2 Diabetes (T2D) and cancer susceptibility. This investigation utilizes genetic data summarized from three reputable sources: the Japanese ENcyclopedia of GEnetic associations by Riken (JENGER), the Asian Genetic Epidemiology Network (AGEN), and the Meta Analyses of Glucose and Insulin-related traits (MAGIC). We explored the associations between exposure datasets, which included T2D, glycated hemoglobin (HbA1c) and fasting glucose (FG) levels, and the risk of several prevalent cancers for the outcome datasets. By analyzing 174 SNPs associated with T2D, 15 SNPs related to FG, and 74 SNPs linked to HbA1c, we discovered a significant inverse relationship between T2D and the majority of cancers, including gastric (OR = 0.875, 95%CI: 0.825–0.928), breast (OR = 0.907, 95%CI: 0.850–0.967), esophageal (OR = 0.761, 95%CI:0.681–0.851), colorectal (OR = 0.877, 95%CI:0.834–0.923), hematological malignancy (OR = 0.837, 95%CI:0.752–0.933), lung (OR = 0.916, 95%CI:0.858–0.977), hepatocellular (OR = 0.865, 95%CI:0.787–0.951), prostate (OR = 0.862, 95%CI:0.812–0.914), and endometrial cancer (OR = 0.841). The power of gastric cancer, breast cancer, esophageal cancer, colorectal cancer and prostate cancer reached the desired 80%. Conversely, we did not observe a reverse correlation between T2D and specific cancers in the East Asian population. There is limited evidence that genetically predicted FG and HbA1c levels are associated with specific cancer. Moreover, conducting multivariable MR analysis did not alter the correlation between T2D and specific tumors. These findings explain the causal associations of genetic liability to T2D with various types of cancers in East Asian ancestry, and this association is not affected by glycemic biomarkers. |
| format | Article |
| id | doaj-art-1748822ff3584b6b93b1cb8f6f240a30 |
| institution | Kabale University |
| issn | 1475-2867 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj-art-1748822ff3584b6b93b1cb8f6f240a302025-08-20T03:46:20ZengBMCCancer Cell International1475-28672025-08-012511910.1186/s12935-025-03929-1A Mendelian randomization study of type 2 diabetes and cancer risk in East AsiansLing Li0Fangxuan Li1Zhanyu Pan2Department of Integrated Traditional and Western Medicine, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for CancerDepartment of Cancer Prevention, Tianjin Medical University Cancer Institute and HospitalDepartment of Integrated Traditional and Western Medicine, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Tianjin’s Clinical Research Center for CancerAbstract Our research aims to explore genetic correlation between T2D predisposition and risks of several cancers, which have been predominantly focused on populations of European ancestry. In an East Asian population, we leverage two-sample Mendelian Randomization to investigate the complex association between Type 2 Diabetes (T2D) and cancer susceptibility. This investigation utilizes genetic data summarized from three reputable sources: the Japanese ENcyclopedia of GEnetic associations by Riken (JENGER), the Asian Genetic Epidemiology Network (AGEN), and the Meta Analyses of Glucose and Insulin-related traits (MAGIC). We explored the associations between exposure datasets, which included T2D, glycated hemoglobin (HbA1c) and fasting glucose (FG) levels, and the risk of several prevalent cancers for the outcome datasets. By analyzing 174 SNPs associated with T2D, 15 SNPs related to FG, and 74 SNPs linked to HbA1c, we discovered a significant inverse relationship between T2D and the majority of cancers, including gastric (OR = 0.875, 95%CI: 0.825–0.928), breast (OR = 0.907, 95%CI: 0.850–0.967), esophageal (OR = 0.761, 95%CI:0.681–0.851), colorectal (OR = 0.877, 95%CI:0.834–0.923), hematological malignancy (OR = 0.837, 95%CI:0.752–0.933), lung (OR = 0.916, 95%CI:0.858–0.977), hepatocellular (OR = 0.865, 95%CI:0.787–0.951), prostate (OR = 0.862, 95%CI:0.812–0.914), and endometrial cancer (OR = 0.841). The power of gastric cancer, breast cancer, esophageal cancer, colorectal cancer and prostate cancer reached the desired 80%. Conversely, we did not observe a reverse correlation between T2D and specific cancers in the East Asian population. There is limited evidence that genetically predicted FG and HbA1c levels are associated with specific cancer. Moreover, conducting multivariable MR analysis did not alter the correlation between T2D and specific tumors. These findings explain the causal associations of genetic liability to T2D with various types of cancers in East Asian ancestry, and this association is not affected by glycemic biomarkers. https://doi.org/10.1186/s12935-025-03929-1Type 2 diabetesCancerMendelian randomization |
| spellingShingle | Ling Li Fangxuan Li Zhanyu Pan A Mendelian randomization study of type 2 diabetes and cancer risk in East Asians Cancer Cell International Type 2 diabetes Cancer Mendelian randomization |
| title | A Mendelian randomization study of type 2 diabetes and cancer risk in East Asians |
| title_full | A Mendelian randomization study of type 2 diabetes and cancer risk in East Asians |
| title_fullStr | A Mendelian randomization study of type 2 diabetes and cancer risk in East Asians |
| title_full_unstemmed | A Mendelian randomization study of type 2 diabetes and cancer risk in East Asians |
| title_short | A Mendelian randomization study of type 2 diabetes and cancer risk in East Asians |
| title_sort | mendelian randomization study of type 2 diabetes and cancer risk in east asians |
| topic | Type 2 diabetes Cancer Mendelian randomization |
| url | https://doi.org/10.1186/s12935-025-03929-1 |
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