Abstract：
BACKGROUND: Observational studies have shown that cholelithiasis and cholecystectomy are associated with the risk of breast cancer (BC) and gynecological cancers, but whether these relationships are causal has not been established and remains controversial.
METHODS: Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers.
RESULTS: The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR] = 1.04, 95% confidence interval [CI]: 1.01-1.06, p = 0.002) and endometrial cancer (EC) (RR = 1.26, 95% CI: 1.02-1.56, p = 0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p = 0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p = 0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p > 0.05).
CONCLUSIONS: This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC.
METHODS: Our study began with a meta-analysis that synthesized data from prior observational studies to examine the association between cholelithiasis, cholecystectomy, and the risk of BC and gynecological cancers. Subsequently, a two-sample Mendelian randomization (MR) analysis was conducted utilizing genetic variant data to investigate the potential causal relationship between cholelithiasis, cholecystectomy, and the aforementioned cancers.
RESULTS: The results of the meta-analysis demonstrated a significant association between cholecystectomy and the risk of BC (risk ratio [RR] = 1.04, 95% confidence interval [CI]: 1.01-1.06, p = 0.002) and endometrial cancer (EC) (RR = 1.26, 95% CI: 1.02-1.56, p = 0.031). Conversely, no significant association was observed between cholelithiasis and the risk of BC, EC, and ovarian cancer. The MR analysis revealed no discernible causal connection between cholelithiasis and overall BC (p = 0.053), as well as BC subtypes (including estrogen receptor-positive/negative). Similarly, there was no causal effect of cholecystectomy on BC risk (p = 0.399) and its subtypes. Furthermore, no causal associations were identified between cholelithiasis, cholecystectomy, and the risk of gynecological cancers (ovarian, endometrial, and cervical cancer [CC]) (all p > 0.05).
CONCLUSIONS: This study does not support a causal link between cholelithiasis and cholecystectomy and an increased risk of female cancers such as breast, endometrial, ovarian, and CC.
摘要：
背景：观察性研究表明，胆石症和胆囊切除术与乳腺癌（BC）和妇科癌症的风险有关，但是这些关系是否是因果关系尚未确定，仍然存在争议。
方法：我们的研究从荟萃分析开始，该分析综合了先前观察性研究的数据，以检查胆石症之间的关联。胆囊切除术,以及BC和妇科癌症的风险。随后，利用遗传变异数据进行了双样本孟德尔随机化（MR）分析，以调查胆石症之间的潜在因果关系，胆囊切除术,和上述癌症。
结果：荟萃分析的结果表明，胆囊切除术与BC的风险（风险比[RR]=1.04，95％置信区间[CI]：1.01-1.06，p=0.002）和子宫内膜癌（EC）（RR=1.26，95％CI：1.02-1.56，p=0.031）之间存在显着关联。相反，未观察到胆石症与BC风险之间的显著关联，EC,和卵巢癌。MR分析显示胆石症和总体BC之间没有明显的因果关系（p=0.053），以及BC亚型（包括雌激素受体阳性/阴性）。同样，胆囊切除术对BC风险(p=0.399)及其亚型无因果关系.此外，未发现胆石症之间的因果关系，胆囊切除术,和妇科癌症的风险(卵巢癌，子宫内膜,和宫颈癌[CC]）（均p>0.05）。
结论：这项研究不支持胆石症和胆囊切除术之间的因果关系和女性癌症的风险增加，如乳腺癌，子宫内膜,卵巢,CC。
方法：我们的研究从荟萃分析开始，该分析综合了先前观察性研究的数据，以检查胆石症之间的关联。胆囊切除术,以及BC和妇科癌症的风险。随后，利用遗传变异数据进行了双样本孟德尔随机化（MR）分析，以调查胆石症之间的潜在因果关系，胆囊切除术,和上述癌症。
结果：荟萃分析的结果表明，胆囊切除术与BC的风险（风险比[RR]=1.04，95％置信区间[CI]：1.01-1.06，p=0.002）和子宫内膜癌（EC）（RR=1.26，95％CI：1.02-1.56，p=0.031）之间存在显着关联。相反，未观察到胆石症与BC风险之间的显著关联，EC,和卵巢癌。MR分析显示胆石症和总体BC之间没有明显的因果关系（p=0.053），以及BC亚型（包括雌激素受体阳性/阴性）。同样，胆囊切除术对BC风险(p=0.399)及其亚型无因果关系.此外，未发现胆石症之间的因果关系，胆囊切除术,和妇科癌症的风险(卵巢癌，子宫内膜,和宫颈癌[CC]）（均p>0.05）。
结论：这项研究不支持胆石症和胆囊切除术之间的因果关系和女性癌症的风险增加，如乳腺癌，子宫内膜,卵巢,CC。
