BACKGROUND: Diabetes mellitus is unfavorably associated with cancer risk. The purpose of this multidisciplinary project was to evaluate a possible association of diabetes mellitus and other comorbidities and their treatment with progression of colorectal cancer. PATIENTS AND METHODS: We investigated the correlation between pathological characteristics and clinical course, including comorbidities in 1004 Czech patients diagnosed and surgically treated for colorectal adenocarcinoma (CRC) between 1999 and 2016. RESULTS: In our data set, CRC patients treated with metformin due to coexisting diabetes mellitus type 2 (T2DM) developed fewer distant metastases which clinically correlates with slower CRC progression. Survival in metformin subgroup was longer, particularly in men with CRC. Osteoporosis may be a negative factor of survival in CRC patients. CONCLUSIONS: Our findings also indicate that aging, higher tumor grade and TNM stage, coexistence of selected endocrine disorders, and metabolic abnormalities may change the tumor microenvironment and impact survival in colorectal cancer, although mechanism of these observations yet to be explained. Patients with diabetes mellitus type 2 treated with metformin may represent the altered microenvironment with specifically tuned metabolic molecular responses and with various epigenetic characteristics. More awareness and increased understanding of the mechanisms underlying the positive effect of metformin on patients' survival could offer insight into new treatment methods and permit more individualized treatment plans.

背景：糖尿病与患癌症的风险有关。这个多学科项目的目的是评估糖尿病和其他合并症及其与大肠癌进展之间的关系。病人与方法：我们调查了病理特征与临床病程之间的相关性，包括1999年至2016年间1004例经诊断和手术治疗的大肠腺癌（CRC）捷克患者的合并症。结果：在我们的数据集中，由于并存的2型糖尿病（T2DM）而接受二甲双胍治疗的CRC患者发生的远处转移较少，这在临床上与CRC进展较慢相关。二甲双胍亚组的生存期更长，尤其是在CRC患者中。骨质疏松可能是CRC患者生存的负面因素。结论：我们的发现还表明，衰老，更高的肿瘤分级和TNM分期，某些内分泌疾病的共存以及代谢异常可能会改变肿瘤的微环境并影响结直肠癌的生存，尽管这些观察结果的机制尚待解释。二甲双胍治疗的2型糖尿病患者可能代表微环境改变，其代谢分子反应经过专门调整，并具有多种表观遗传学特征。对二甲双胍对患者生存产生积极影响的潜在机制的更多认识和更多理解可以为新的治疗方法提供见识，并允许制定更多的个性化治疗计划。