■胃癌(GC)是全球癌症死亡的第三大原因,甲状腺功能减退已被确定为潜在的影响因素。尽管已知甲状腺功能减退症和各种癌症之间的关联,甲状腺功能减退症和GC之间的因果关系和这种关系的潜在介质仍不清楚.本研究旨在使用孟德尔随机化(MR)阐明这些关系。
■利用来自FinnGen和MRC综合流行病学单位开放全基因组关联研究(GWAS)数据库的遗传变异信息,我们进行了单变量和多变量MR分析,以探讨甲状腺功能减退症与GC风险之间的因果关系.分析针对BMI等混杂因素进行了调整,吸烟状况,和酒精的摄入,并包括介体MR分析以检查高胆固醇的作用。
■我们发现甲状腺功能减退与GC风险之间存在显著的负相关(OR=0.93,95%CI=0.89-0.98,P=0.003),没有反向因果关系或多效性的证据。对幽门螺杆菌感染的调整削弱了这种联系。调解员分析强调了高胆固醇水平,慢性乙型肝炎感染,糖尿病/内分泌疾病状态是甲状腺功能减退对GC风险的保护作用的重要媒介。
■我们的研究结果表明,甲状腺功能减退可能会对GC产生保护作用,部分是由高胆固醇和其他因素介导的。这些结果强调了甲状腺功能和代谢健康在GC风险中的重要性,为预防策略提供新的见解,并强调需要进一步研究这些复杂的关联。
UNASSIGNED: Gastric cancer (GC) is the third leading cause of cancer death worldwide, and hypothyroidism has been identified as a potential influencing factor. Despite known associations between hypothyroidism and various cancers, the causal link between hypothyroidism and GC and potential mediators of this relationship remains unclear. This study aimed to clarify these relationships using Mendelian randomization (MR).
UNASSIGNED: Utilizing genetic variant information from the FinnGen and MRC Integrative Epidemiology Unit open genome-wide association studies (GWAS) databases, we conducted univariable and multivariable MR analyses to explore the causal relationship between hypothyroidism and GC risk. The analysis was adjusted for confounders such as BMI, smoking status, and alcohol intake, and included mediator MR analysis to examine the role of high cholesterol.
UNASSIGNED: We identified a significant inverse association between hypothyroidism and GC risk (OR = 0.93, 95% CI= 0.89-0.98, P = 0.003), with no evidence of reverse causation or pleiotropy. Adjustments for Helicobacter pylori infection weakened this association. Mediator analysis highlighted high cholesterol levels, chronic hepatitis B infection, and diabetes/endocrine disease status as significant mediators of the protective effect of hypothyroidism on GC risk.
UNASSIGNED: Our findings suggest that hypothyroidism may confer a protective effect against GC, mediated in part by high cholesterol and other factors. These results underscore the importance of thyroid function and metabolic health in GC risk, offering new insights for preventive strategies and highlighting the need for further research into these complex associations.