Prognostic Role of TP53 and ARID1A Mutations in Alcohol-Consuming Patients With Uterine Endometrioid Carcinoma

Samenvatting

Uterine endometrioid carcinoma (UEC) is the most common subtype of endometrial cancer. This study aimed to investigate the prognostic relevance of TP53 and ARID1A mutations in alcohol-consuming UEC patients using publicly available TCGA data. A total of 207 UEC patients were identified from the TCGA CPTAC-3 project. Alcohol consumption status was extracted from self-reported clinical data. Patients were grouped into alcohol consumers and nonconsumers. Kaplan-Meier survival estimates and multivariable Cox proportional hazards models were used to evaluate the association between gene mutation status and overall survival, adjusted for age, stage, and grade. Sensitivity analyses excluded deaths within the first year. Out of 207 patients, 47 (22.7%) reported alcohol consumption. TP53 mutations were more prevalent in alcohol consumers compared with nonconsumers (36.2% vs. 21.3%, P =0.037). In the alcohol-consuming subgroup, patients with wild-type TP53 had significantly worse survival than those with TP53 mutations in sensitivity analysis (HR=2.85; 95% CI: 1.01-8.05; P =0.047). ARID1A wild-type status was associated with increased mortality risk compared with mutated ARID1A in adjusted models (HR=4.00; 95% CI: 1.45-11.01; P =0.007). No statistically significant survival differences were found for PTEN , PIK3CA , or KRAS mutations. TP53 and ARID1A mutation status may have prognostic relevance among alcohol-consuming patients with UEC. These findings suggest a possible gene-environment interaction in endometrial cancer and support the need for further validation through prospective studies.