Introduction

Recently, sub-classification of steatotic liver disease (SLD) has been updated by revising non-alcoholic fatty liver disease (NAFLD) as metabolic dysfunction-associated steatotic liver disease (MASLD). In this new nomenclature, emphasis was on the etiology of SLD, primarily at factors of metabolic syndrome and alcohol intake. However, associations between MASLD and gastrointestinal tract cancers other than liver cancer in relation to alcohol intake still require further analysis.

Aims & Methods

We investigated the relationship between the incidence of three gastrointestinal tract cancers (esophageal, stomach, and colorectal) and MASLD or alcohol related-SLD in diabetic patients. Using a retrospective screening cohort of National Health Insurance Service, individuals with type 2 diabetes from 2009 to 2012 were enrolled with their disease status being monitored until 2021. Fatty liver index (FLI) score described by Bedogni et al. (2006) was used to stratify the probability of hepatic steatosis. No steatosis (NS), indeterminate steatosis (IS), and steatosis-probable (PS) group were defined as FLI score 0 to < 30, 30< to ≤60, and >60, respectively. SLD was assumed if FLI score ≥ 30, and MASLD was defined as having at least 1 adult criteria provided by the American Association for the Study of Liver Diseases (AASLD). 2,746,079 subjects were classified into following subgroups: group 1: no steatosis, group 2: MASLD alone, group 3: MASLD with other liver disease, group 4: MASLD with heavy alcohol intake (metALD, 30-60g/d for men and 20-50g/d for women), and group 5: alcoholic liver disease (alcohol intake ≥ 60g/d for men and ≥50g/d for women) with metabolic syndrome. Adjusted hazard ratios (aHR) for each gastrointestinal tract cancer were estimated by incorporating multivariate Cox proportional hazards model.

Results

Compared with group 1 (reference), group 2 showed increased risks of stomach and colorectal cancers (aHR [95% confidence interval (CI)]: 1.06 [1.04-1.09] and 1.17 [1.14-1.19] respectively), but a decreased risk of esophageal cancer (0.81 [0.74-0.88]). In all gastrointestinal tract cancers, the risk of developing cancer compared to group 1 tended to increase from group 3 to group 5 (aHRs in groups 3, 4, 5: 1.40, 1.74, 2.36 in esophageal cancer; 1.13, 1.20, 1.22 in stomach cancer; 1.24, 1.33, 1.34 in colorectal cancer, respectively; all p for trend < 0.0001). Subgroup analysis by probability of steatosis in non-drinkers showed that stomach and colorectal cancer risk was positively correlated with higher likelihood of liver steatosis (aHR for NS, IS, PS: 1.00, 1.05, 1.11 for stomach cancer and 1.00, 1.15, 1.27 for colorectal cancer, respectively, p for trend < 0.05). However, this correlation was not demonstrated in esophageal cancer (aHR for NS, IS, PS:1.00, 0.95, 1.08 for esophageal cancer).

Conclusion

In patients with diabetes, MASLD itself is associated with an increased risk of stomach and colorectal cancers but is likely associated with a reduced risk of esophageal cancer. Hepatic steatosis may be associated with higher risk of stomach and colorectal cancers, but not esophageal cancer. Amount of alcohol consumption is confirmed to increase the risk of these cancers regardless of the presence of SLD.

References

1. Rinella, Mary E. "Examining the Nomenclature Change From NAFLD and NASH to MASLD and MASH." Gastroenterology & Hepatology 19.11 (2023): 697.
2. Bedogni, Giorgio, et al. "The Fatty Liver Index: a simple and accurate predictor of hepatic steatosis in the general population." BMC gastroenterology 6 (2006): 1-7.
3. Dabo, Bashir, et al. "The association between diabetes and gastric cancer: results from the Stomach Cancer Pooling Project Consortium." European Journal of Cancer Prevention 31.3 (2022): 260-269.
4. Lee, Hokyou, et al. "Metabolic Dysfunction–Associated Fatty Liver Disease Increases Colon Cancer Risk: A Nationwide Cohort Study." Clinical and translational gastroenterology 13.1 (2022): e00435.