Association between gallstone disease and subsequent risk of sessile serrated adenoma/polyp (SSA/P).

越来越多的证据表明，与传统腺瘤不同、发展途径不同的无柄锯齿状腺瘤/息肉（SSA/P）可能是近端结肠癌的重要前体病变。鉴于这些病变的标准分类直到2010年才被引入，很少有加重因素和分子途径被确定并进一步探索。除了BMI和糖摄入量等生活方式因素外，几乎没有其他因素与它们的发展有关。它们产生的途径尚未被探索，这可能有助于SSA/Ps的筛选和管理。与以染色体不稳定性为特征的传统腺瘤相比，锯齿状病变的发展被认为是由微卫星不稳定性（MSI）驱动的。基于MSI与炎症的密切关系，这些病变可能比传统腺瘤与结肠癌相关炎症活动的相关性更强。另一个与慢性炎症密切相关的过程是胆结石的形成。胆结石病（GD）的发生主要与营养因素有关，但也与多种其他因素相关，各种回顾性和前瞻性研究对其存在进行了大量探讨。事实上，慢性炎症是胆囊癌日益增长的基础，而GD和胰腺癌之间也有很强的联系。许多队列研究仅基于胆囊切除术后的状态将右侧结肠癌与胆结石疾病联系起来，但直到最近，这些研究仅基于胆囊切除术，而不是基于筛查数据。GD与SSA/P风险之间的相关性尚未探讨。这是一个为期24个月的项目，包括队列研究分析、验证分析和病例对照研究。该项目将利用哈佛队列研究和合作伙伴研究患者数据登记处（RPDR）的数据来检查这两种胃肠道疾病之间的联系，并通过生物标志物分析询问潜在的机制。这一发现将对结直肠癌的预防具有重要的临床意义。

Increasing evidence suggests that sessile serrated adenoma/polyp (SSA/P, which is different from conventional adenoma and develops over a different pathway) may be an important precursor lesion for proximal colon cancer. Given that the standard classification of these lesions has not been introduced until 2010, few aggravating factors and molecular pathways have been identified and further explored . Apart from lifestyle factors such as BMI and sugar intake, few other factors have been correlated to their development. The pathways from which they arise have not yet been explored, something which could facilitate screening and thus management of SSA/Ps. Compared to conventional adenomas that are characterized by chromosomal instability, the development of serrated lesions has been suggested to be driven by microsatellite instability (MSI). Based on the close relationship between MSI and inflammation, these lesions may be more strongly associated with the colon cancer-related inflammatory activities than conventional adenoma. A process which also has a strong connection with chronic inflammation is the development of gallstones. Gallstone disease (GD) arises mainly due to nutrition factors but also correlates with various others, while its presence has been vastly explored is various retrospective and prospective studies. In fact chronic inflammation is the growing ground for gallbladder cancer while a strong connection between GD and pancreatic cancer has also been shown. A number of cohort studies have associated right-side colon cancer with gallstone disease based only on the status post cholecystectomy but until recently only based on the cholecystectomy and not based on screening data. A correlation between GD and the risk for SSA/P has not yet been explored. This is a 24-month project entailing a cohort study analysis, a validation analysis and a case control study. The project will leverage data from both the Harvard cohort studies and the Partners Research Patient Data Registry (RPDR) to examine the link between the two gastrointestinal diseases and interrogate potential mechanisms through biomarker analysis. The findings will have important clinical implications for colorectal cancer prevention.