Aim: The recently updated steatotic liver disease (SLD) nomenclature provides a refined classification accounting for both metabolic dysfunction and alcohol exposure. However, the relationship between SLD subtypes and upper gastrointestinal (UGI) cancer risk remains unclear. Methods: We analyzed 456,367 UK Biobank participants, categorizing them into non-SLD, metabolic dysfunction-associated steatotic liver disease with no alcohol (MASLD1), MASLD with minimal alcohol use (MASLD2), metabolic dysfunction-associated alcohol-related liver disease (MetALD), and alcohol-associated liver disease (ALD) groups. Cox proportional hazards models estimated cancer risks over a median 13-year follow-up, with histologic subtype-specific analyses. Results: Compared to non-SLD, esophageal cancer risk was significantly elevated in all SLD groups with any alcohol consumption (MASLD2, MetALD, and ALD), but not in purely metabolic SLD without alcohol (MASLD1). This association was driven by adenocarcinoma subtype, with hazard ratios ranging from 1.67 to 1.80 in alcohol-exposed SLD groups. For gastric cancer, elevated risk was observed primarily in ALD and MetALD groups, affecting intestinal-type cancers. Squamous cell esophageal cancer and non-intestinal gastric cancer showed no significant associations. Conclusions: Upper GI cancer risk in SLD patients is significantly modified by alcohol consumption, with combined metabolic dysfunction and alcohol exposure conferring the highest risks for esophageal adenocarcinoma and intestinal-type gastric cancer. Clinically, these findings suggest that SLD patients with any level of alcohol consumption require heightened cancer surveillance. Even minimal alcohol intake substantially increases cancer risk in metabolically compromised individuals, supporting alcohol reduction as a key preventive strategy.
目的：近期更新的脂肪性肝病（SLD）命名法提供了更精细的分类，同时考虑了代谢功能障碍和酒精暴露因素。然而，SLD亚型与上消化道（UGI）癌症风险之间的关系尚不明确。方法：我们分析了英国生物样本库中的456,367名参与者，将其分为非SLD组、无酒精的代谢功能障碍相关脂肪性肝病（MASLD1）组、少量饮酒的MASLD（MASLD2）组、代谢功能障碍相关酒精性肝病（MetALD）组以及酒精相关肝病（ALD）组。通过Cox比例风险模型评估中位随访13年期间的癌症风险，并进行组织学亚型特异性分析。结果：与非SLD组相比，所有存在酒精摄入的SLD组（MASLD2、MetALD和ALD）的食管癌风险均显著升高，但无酒精的纯代谢性SLD组（MASLD1）未观察到风险升高。这种关联主要由腺癌亚型驱动，在酒精暴露的SLD组中风险比范围为1.67至1.80。对于胃癌，风险升高主要在ALD和MetALD组中观察到，且主要影响肠型胃癌。食管鳞状细胞癌和非肠型胃癌未显示显著关联。结论：SLD患者的上消化道癌症风险受酒精摄入显著影响，代谢功能障碍与酒精暴露共同作用导致食管腺癌和肠型胃癌的风险最高。临床意义上，这些发现提示任何程度饮酒的SLD患者均需加强癌症监测。即使在代谢功能受损个体中，极少量酒精摄入也会显著增加癌症风险，这支持了减少酒精摄入作为关键预防策略的重要性。
肿瘤(癌症)患者之家