Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study

IntroductionObservational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establis...

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Main Authors: Yingtong Wu, Yinggang Che, Yong Zhang, Yanlu Xiong, Chen Shu, Jun Jiang, Gaozhi Li, Lin Guo, Tianyun Qiao, Shuwen Li, Ou Li, Ning Chang, Xinxin Zhang, Minzhe Zhang, Dan Qiu, Hangtian Xi, Jinggeng Li, Xiangxiang Chen, Mingxiang Ye, Jian Zhang
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Language:English
Published: Frontiers Media S.A. 2024-06-01
Series:Frontiers in Genetics
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Online Access:https://www.frontiersin.org/articles/10.3389/fgene.2024.1293668/full
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author Yingtong Wu
Yingtong Wu
Yinggang Che
Yong Zhang
Yanlu Xiong
Chen Shu
Jun Jiang
Gaozhi Li
Lin Guo
Tianyun Qiao
Shuwen Li
Ou Li
Ning Chang
Xinxin Zhang
Minzhe Zhang
Dan Qiu
Hangtian Xi
Jinggeng Li
Xiangxiang Chen
Mingxiang Ye
Jian Zhang
author_facet Yingtong Wu
Yingtong Wu
Yinggang Che
Yong Zhang
Yanlu Xiong
Chen Shu
Jun Jiang
Gaozhi Li
Lin Guo
Tianyun Qiao
Shuwen Li
Ou Li
Ning Chang
Xinxin Zhang
Minzhe Zhang
Dan Qiu
Hangtian Xi
Jinggeng Li
Xiangxiang Chen
Mingxiang Ye
Jian Zhang
author_sort Yingtong Wu
collection DOAJ
description IntroductionObservational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation.MethodsFor Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments.ResultsOur results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34–4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32–3.43]), benign neoplasm of the larynx (2.01 [1.36–2.96]), melanoma (1.74 [1.17–2.59]), follicular lymphoma (1.50 [1.06–2.11]), autoimmune thyroiditis (2.47 [1.49–4.08]), and autoimmune hyperthyroidism (1.93 [1.17–3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland.ConclusionCasting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.
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spelling doaj-art-1bfadc0ab16a43f897c8c4bcd9d50f7a2025-08-20T03:39:40ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-06-011510.3389/fgene.2024.12936681293668Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization studyYingtong Wu0Yingtong Wu1Yinggang Che2Yong Zhang3Yanlu Xiong4Chen Shu5Jun Jiang6Gaozhi Li7Lin Guo8Tianyun Qiao9Shuwen Li10Ou Li11Ning Chang12Xinxin Zhang13Minzhe Zhang14Dan Qiu15Hangtian Xi16Jinggeng Li17Xiangxiang Chen18Mingxiang Ye19Jian Zhang20Department of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaFirst Sanatorium, Air Force Healthcare Center for Special Services, Hangzhou, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, Air-Force Medical University, Xi’an, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, Air-Force Medical University, Xi’an, ChinaDepartment of Health Service, Air-Force Medical University, Xi’an, China94498th Unit of the People’s Liberation Army of China, Nanyang, ChinaDepartment of Obstetrics and Gynecology, Tangdu Hospital, Air-Force Medical University, Xi’an, ChinaDepartment of Thoracic Surgery, Tangdu Hospital, Air-Force Medical University, Xi’an, ChinaFirst Sanatorium, Air Force Healthcare Center for Special Services, Hangzhou, ChinaFirst Sanatorium, Air Force Healthcare Center for Special Services, Hangzhou, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaCollege of Pulmonary and Critical Care Medicine, the 8th Medical Centre of Chinese PLA General Hospital, Beijing, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaDepartment of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, ChinaDepartment of Pulmonary Medicine, Xi'an People's Hospital, Xi’an, ChinaIntroductionObservational investigations have examined the impact of glucosamine use on the risk of cancer and non-neoplastic diseases. However, the findings from these studies face limitations arising from confounding variables, reverse causation, and conflicting reports. Consequently, the establishment of a causal relationship between habitual glucosamine consumption and the risk of cancer and non-neoplastic diseases necessitates further investigation.MethodsFor Mendelian randomization (MR) investigation, we opted to employ single-nucleotide polymorphisms (SNPs) as instruments that exhibit robust associations with habitual glucosamine consumption. We obtained the corresponding effect estimates of these SNPs on the risk of cancer and non-neoplastic diseases by extracting summary data for genetic instruments linked to 49 varied cancer types amounting to 378,284 cases and 533,969 controls, as well as 20 non-neoplastic diseases encompassing 292,270 cases and 842,829 controls. Apart from the primary analysis utilizing inverse-variance weighted MR, we conducted two supplementary approaches to account for potential pleiotropy (MR-Egger and weighted median) and assessed their respective MR estimates. Furthermore, the results of the leave-one-out analysis revealed that there were no outlying instruments.ResultsOur results suggest divergence from accepted biological understanding, suggesting that genetically predicted glucosamine utilization may be linked to an increased vulnerability to specific illnesses, as evidenced by increased odds ratios and confidence intervals (95% CI) for diseases, such as malignant neoplasm of the eye and adnexa (2.47 [1.34–4.55]), benign neoplasm of the liver/bile ducts (2.12 [1.32–3.43]), benign neoplasm of the larynx (2.01 [1.36–2.96]), melanoma (1.74 [1.17–2.59]), follicular lymphoma (1.50 [1.06–2.11]), autoimmune thyroiditis (2.47 [1.49–4.08]), and autoimmune hyperthyroidism (1.93 [1.17–3.18]). In contrast to prior observational research, our genetic investigations demonstrate a positive correlation between habitual glucosamine consumption and an elevated risk of sigmoid colon cancer, lung adenocarcinoma, and benign neoplasm of the thyroid gland.ConclusionCasting doubt on the purported purely beneficial association between glucosamine ingestion and prevention of neoplastic and non-neoplastic diseases, habitual glucosamine ingestion exhibits dichotomous effects on disease outcomes. Endorsing the habitual consumption of glucosamine as a preventative measure against neoplastic and non-neoplastic diseases cannot be supported.https://www.frontiersin.org/articles/10.3389/fgene.2024.1293668/fullglucosaminecancer riskMendelian randomizationsingle-nucleotide polymorphismscausality
spellingShingle Yingtong Wu
Yingtong Wu
Yinggang Che
Yong Zhang
Yanlu Xiong
Chen Shu
Jun Jiang
Gaozhi Li
Lin Guo
Tianyun Qiao
Shuwen Li
Ou Li
Ning Chang
Xinxin Zhang
Minzhe Zhang
Dan Qiu
Hangtian Xi
Jinggeng Li
Xiangxiang Chen
Mingxiang Ye
Jian Zhang
Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study
Frontiers in Genetics
glucosamine
cancer risk
Mendelian randomization
single-nucleotide polymorphisms
causality
title Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study
title_full Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study
title_fullStr Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study
title_full_unstemmed Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study
title_short Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study
title_sort association between genetically proxied glucosamine and risk of cancer and non neoplastic disease a mendelian randomization study
topic glucosamine
cancer risk
Mendelian randomization
single-nucleotide polymorphisms
causality
url https://www.frontiersin.org/articles/10.3389/fgene.2024.1293668/full
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