Division of Liver Surgery, Department of General Surgery, West China Hospital, Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, China.
Division of Vascular Surgery, Department of General Surgery, West China Hospital of Sichuan University, No. 37 GuoXue Alley, Chengdu, 610041, China.
BMC Cancer. 2024 Sep 27;24(1):1192. doi: 10.1186/s12885-024-12906-2.
The association between gallstones/cholecystectomy and cancer remains inconclusive in the current literature. This study aimed to explore the causal connections between gallstones/cholecystectomy and cancer risk by utilizing a bidirectional two-sample multivariable Mendelian randomization approach with Genome-Wide Association Studies data.
Utilizing Genome-Wide Association Studies data from the UK Biobank and FinnGen, this research employed multivariable Mendelian randomization analyses to explore the impact of gallstones and cholecystectomy on the risk of 33 distinct cancer types. Instrumental variables for gallstones and cholecystectomy were carefully selected to ensure robust analyses, and sensitivity and heterogeneity tests were conducted to verify the findings' validity.
Multivariable Mendelian randomization analysis, incorporating data from more than 450,000 individuals for gallstones and cholecystectomy, revealed nuanced associations with cancer risk. Cholecystectomy was associated with a significantly increased risk of nonmelanoma skin cancer (OR = 1.59, 95% CI: 1.21 to 2.10, P = 0.001), while gallstones were linked to a decreased risk of the same cancer type (OR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002). Interestingly, the analysis also suggested that cholecystectomy may lower the risk of small intestine tumors (OR = 0.18, 95% CI: 0.043 to 0.71, P = 0.015), with gallstones showing an inverse relationship, indicating an increased risk (OR = 6.41, 95% CI: 1.48 to 27.80, P = 0.013).
The multivariable Mendelian randomization analysis highlights the differential impact of gallstones and cholecystectomy on cancer risk, specifically for nonmelanoma skin cancer and small intestine tumors. These results underscore the importance of nuanced clinical management strategies and further research to understand the underlying mechanisms and potential clinical implications of gallstone disease and cholecystectomy on cancer risk.
目前的文献中，胆结石/胆囊切除术与癌症之间的关联仍不确定。本研究旨在利用基于全基因组关联研究数据的双向两样本多变量孟德尔随机化方法，探索胆结石/胆囊切除术与癌症风险之间的因果关系。
利用英国生物库和芬兰基因研究的全基因组关联研究数据，本研究采用多变量孟德尔随机化分析，探讨了胆结石和胆囊切除术对 33 种不同癌症类型风险的影响。仔细选择了胆结石和胆囊切除术的工具变量，以确保分析的稳健性，并进行了敏感性和异质性检验，以验证研究结果的有效性。
多变量孟德尔随机化分析纳入了超过 45 万名个体的胆结石和胆囊切除术数据，揭示了与癌症风险的细微关联。胆囊切除术与非黑色素瘤皮肤癌的风险显著增加相关（OR=1.59，95%CI：1.21 至 2.10，P=0.001），而胆结石与同一癌症类型的风险降低相关（OR=0.63，95%CI：0.47 至 0.84，P=0.002）。有趣的是，分析还表明胆囊切除术可能降低小肠肿瘤的风险（OR=0.18，95%CI：0.043 至 0.71，P=0.015），而胆结石则呈相反关系，表明风险增加（OR=6.41，95%CI：1.48 至 27.80，P=0.013）。
多变量孟德尔随机化分析强调了胆结石和胆囊切除术对癌症风险的不同影响，特别是对非黑色素瘤皮肤癌和小肠肿瘤。这些结果突出了实施细致临床管理策略的重要性，并进一步研究以了解胆结石病和胆囊切除术对癌症风险的潜在机制和临床意义。
