研究动态
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遗传代理葡萄糖胺与癌症和非肿瘤疾病风险之间的关联:孟德尔随机研究。

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

发表日期:2024
作者: 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
来源: Frontiers in Genetics

摘要:

观察性调查研究了葡萄糖胺的使用对癌症和非肿瘤疾病风险的影响。然而,这些研究的结果面临着由于混杂变量、反向因果关系和相互矛盾的报告而产生的局限性。因此,建立习惯性葡萄糖胺消耗与癌症和非肿瘤疾病风险之间的因果关系需要进一步研究。对于孟德尔随机化(MR)研究,我们选择采用单核苷酸多态性(SNP)作为表现出稳健的工具与习惯性葡萄糖胺消耗有关。我们通过提取与 49 种不同癌症类型(总计 378,284 例病例和 533,969 例对照)以及 20 种非肿瘤性疾病(涵盖 292,270 例)相关的遗传仪器的汇总数据,获得了这些 SNP 对癌症和非肿瘤疾病风险的相应影响估计。病例和 842,829 例对照。除了利用逆方差加权 MR 进行初步分析外,我们还进行了两种补充方法来解释潜在的多效性(MR-Egger 和加权中位数),并评估了它们各自的 MR 估计值。此外,留一法分析的结果显示,不存在任何异常仪器。我们的结果表明与公认的生物学理解存在差异,这表明基因预测的葡萄糖胺利用可能与对特定疾病的脆弱性增加有关,这一点可以通过增加疾病的比值比和置信区间 (95% CI),例如眼睛和附件恶性肿瘤 (2.47 [1.34-4.55])、肝脏/胆管良性肿瘤 (2.12 [1.32-3.43])、良性肿瘤喉部肿瘤 (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]) 和自身免疫性甲状腺功能亢进症 (1.93 [1.93] 1.17-3.18])。与之前的观察性研究相反,我们的基因研究表明,习惯性葡萄糖胺消耗与乙状结肠癌、肺腺癌和甲状腺良性肿瘤风险升高之间存在正相关关系。人们对所谓的葡萄糖胺摄入与甲状腺良性肿瘤之间的纯粹有益关联表示怀疑。预防肿瘤和非肿瘤疾病,习惯性葡萄糖胺摄入对疾病结果表现出双重影响。不能支持将习惯性消费氨基葡萄糖作为预防肿瘤和非肿瘤疾病的措施。版权所有 © 2024 Wu, Che, Zhuang, Xiong, Shu, Jiang, Li,Guo, Qiao, Li, Li, Chang, Zhu,张、邱、习、李、陈、叶、张。
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.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.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.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.Copyright © 2024 Wu, Che, Zhang, Xiong, Shu, Jiang, Li, Guo, Qiao, Li, Li, Chang, Zhang, Zhang, Qiu, Xi, Li, Chen, Ye and Zhang.