Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jun 27:15:1293668.
doi: 10.3389/fgene.2024.1293668. eCollection 2024.

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

Yingtong Wu #  1   2 , Yinggang Che #  1 , Yong Zhang  1 , Yanlu Xiong  3 , Chen Shu  3 , Jun Jiang  4 , Gaozhi Li  5 , Lin Guo  6 , Tianyun Qiao  3 , Shuwen Li  2 , Ou Li  2 , Ning Chang  1 , Xinxin Zhang  7 , Minzhe Zhang  1 , Dan Qiu  1 , Hangtian Xi  1 , Jinggeng Li  1 , Xiangxiang Chen  1 , Mingxiang Ye  8 , Jian Zhang  1
Affiliations

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

Yingtong Wu et al. Front Genet. .

Erratum in

Abstract

Introduction: Observational 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.

Methods: For 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.

Results: Our 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.

Conclusion: Casting 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.

Keywords: Mendelian randomization; cancer risk; causality; glucosamine; single-nucleotide polymorphisms.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Conceptual framework of the Mendelian randomization study. The overarching objective of this study is to utilize genetic variants as instrumental variables (IVs) to estimate the unbiased causal relationship between regular glucosamine use and cancer and non-neoplastic disease risk. Toward this end, the association of IVs with both regular glucosamine use and cancer/non-neoplastic disease risk is leveraged to estimate the corresponding association between regular glucosamine use and these outcomes.
FIGURE 2
FIGURE 2
The association between genetically regular glucosamine use and risk of site-specific cancers. SNP, single-nucleotide polymorphism; OR, odds ratio; CI, confidence interval; NA, not applicable; ER, estrogen receptor; ILCCO, International Lung Cancer Consortium; BCAC, Breast Cancer Association Consortium; OCAC, Ovarian Cancer Association Consortium. (A) p-value for the association between genetically regular glucosamine use and cancer risk was estimated using random-effects inverse-variance weighting. (B) p-value for assessing heterogeneity among single-nucleotide polymorphisms within the instrumental variable.
FIGURE 3
FIGURE 3
The association between genetically regular glucosamine use and risk of non-neoplastic diseases. SNP, single-nucleotide polymorphism; OR, odds ratio; CI, confidence interval; NA, not applicable; IMSGC, International Multiple Sclerosis Genetics Consortium; PGC, Psychiatric Genomics Consortium; IPDGC, International Parkinson’s Disease Genomics Consortium. (A) p-value for the association between genetically regular glucosamine use and cancer risk was estimated using random-effects inverse-variance weighting. (B) p-value for assessing heterogeneity among single-nucleotide polymorphisms within the instrumental variable.
FIGURE 4
FIGURE 4
Comparison of Mendelian randomization investigation and prospective observational studies of the association between habitual glucosamine consumption and the risk of disease.
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines (2000). Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum. 43 (9), 1905–1915. 10.1002/1529-0131(200009)43:9<1905::AID-ANR1>3.0.CO;2-P - DOI - PubMed
    1. Arden N. K., Perry T. A., Bannuru R. R., Bruyere O., Cooper C., Haugen I. K., et al. (2021). Non-surgical management of knee osteoarthritis: comparison of ESCEO and OARSI 2019 guidelines. Nat. Rev. Rheumatol. 17 (1), 59–66. 10.1038/s41584-020-00523-9 - DOI - PubMed
    1. Azuma K., Osaki T., Kurozumi S., Kiyose M., Tsuka T., Murahata Y., et al. (2015). Anti-inflammatory effects of orally administered glucosamine oligomer in an experimental model of inflammatory bowel disease. Carbohydr. Polym. 115, 448–456. 10.1016/j.carbpol.2014.09.012 - DOI - PubMed
    1. Bhimani J., O’Connell K., Kuk D., Du M., Navarro S. L., Kantor E. D. (2023). Glucosamine and chondroitin use and mortality among adults in the United States from 1999 to 2014. J. Integr. Complement. Med. 29, 492–500. 10.1089/jicm.2022.0783 - DOI - PMC - PubMed
    1. Bosmann H. B. (1971). Inhibition of protein, glycoprotein, ribonucleic acid and deoxyribonucleic acid synthesis by D-glucosamine and other sugars in mouse leukemic cells L5178Y and selective inhibition in SV-3T3 compared with 3T3 cells. Biochim. Biophys. Acta 240 (1), 74–93. 10.1016/0005-2787(71)90515-6 - DOI - PubMed

LinkOut - more resources