Table5_Association between genetically proxied glucosamine and risk of cancer and non-neoplastic disease: A Mendelian randomization study.XLSX

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.

引言：既往观察性研究已探讨氨基葡萄糖（glucosamine）摄入对癌症及非肿瘤性疾病发病风险的影响，但此类研究结果存在局限，包括混杂变量、反向因果关联以及研究结论不一致等问题。因此，明确习惯性氨基葡萄糖摄入与癌症及非肿瘤性疾病发病风险之间的因果关系，仍需进一步探究。
方法：本研究采用孟德尔随机化（Mendelian randomization, MR）设计，选用与习惯性氨基葡萄糖摄入存在强关联的单核苷酸多态性（single-nucleotide polymorphisms, SNPs）作为工具变量。通过提取涵盖49种不同癌症类型的遗传工具变量汇总数据（共378284例病例、533969例对照），以及20种非肿瘤性疾病的相关汇总数据（共292270例病例、842829例对照），我们获取了这些工具变量对癌症及非肿瘤性疾病发病风险的效应估计值。本研究以逆方差加权孟德尔随机化（inverse-variance weighted MR, IVW-MR）作为主要分析方法，同时采用MR-Egger法和加权中位数法两种补充分析策略以校正潜在的多效性偏倚，并分别评估其效应估计结果。此外，留一法分析结果显示，未存在异常工具变量。
结果：本研究结果与公认的生物学认知不符，提示遗传学预测的氨基葡萄糖摄入或与特定疾病的发病风险升高存在关联，具体表现为以下疾病的比值比（odds ratio, OR）及95%置信区间（confidence interval, CI）升高：眼及附属器恶性肿瘤（2.47 [1.34~4.55]）、肝/胆管良性肿瘤（2.12 [1.32~3.43]）、喉部良性肿瘤（2.01 [1.36~2.96]）、黑色素瘤（1.74 [1.17~2.59]）、滤泡性淋巴瘤（1.50 [1.06~2.11]）、自身免疫性甲状腺炎（2.47 [1.49~4.08]）以及自身免疫性甲状腺功能亢进症（1.93 [1.17~3.18]）。与既往观察性研究不同，本遗传学分析显示，习惯性氨基葡萄糖摄入与乙状结肠癌、肺腺癌及甲状腺良性肿瘤的发病风险升高呈正相关。
结论：本研究对“氨基葡萄糖摄入可预防肿瘤性及非肿瘤性疾病”这一公认的纯获益关联提出质疑，结果显示习惯性氨基葡萄糖摄入对疾病转归存在双向效应。因此，不支持将习惯性氨基葡萄糖摄入作为肿瘤性及非肿瘤性疾病的预防措施。