Pathophysiological Characteristics Linking Type 2 Diabetes Mellitus and Colorectal Neoplasia

Grega, Tomáš; Vojtechova, Gabriela; Gregová, Monika; Zavoral, Miroslav; Suchánek, Štěpán

doi:10.33549/physiolres.934631

Cited by 7 publications

(3 citation statements)

References 90 publications

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“…Obesity causes an increased production of adipocytes and cytokine (tumor necrosis factor and IL-6), which may damage cellular DNA, increase angiogenesis and promote cell proliferation. Furthermore, obesity causes a state of insulin resistance, there is increased insulin and insulin-dependent growth factors [ 43 , 44 ]. Several studies have shown that obesity in adolescence and type 2 diabetes are associated with increased incidence of EOCRC and related mortality.…”

Section: Modifiable Risk Factors For Early-onset Colorectal Cancermentioning

confidence: 99%

Early-Onset Colorectal Cancer: Current Insights

Ullah,

Pillai,

Omar

et al. 2023

Cancers

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Over the past decade, the incidence of colorectal cancer has increased in individuals under the age of 50 years. Meanwhile, the incidence has gradually decreased in the older population. As described herein, we reviewed the available literature to summarize the current landscape of early-onset colorectal cancer, including risk factors, clinicopathological presentation, genetic makeup of patients, and management. Currently, early-onset colorectal cancer is treated similarly as late-onset colorectal cancer, yet the available literature shows that early-onset colorectal cancer is more aggressive and different, and this remains a significant unmet need. A detailed understanding of early-onset colorectal cancer is needed to identify risk factors for the increased incidence and tailor treatments accordingly.

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Section: Modifiable Risk Factors For Early-onset Colorectal Cancermentioning

confidence: 99%

Early-Onset Colorectal Cancer: Current Insights

Ullah,

Pillai,

Omar

et al. 2023

Cancers

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“…Epidemiological and biological evidence suggests that individuals with diabetes diagnoses may be at increased risk for colorectal cancer (CRC) . The metabolic dysregulation that occurs in diabetes may contribute to CRC carcinogenesis and proliferation through inflammation and oxidative stress-driven signaling alterations . Meta-analyses report associations between type 2 diabetes and increased risk of CRC, with risk ratios ranging from 1.2 to 1.4 .…”

Section: Introductionmentioning

confidence: 99%

“…6,7 The metabolic dysregulation that occurs in diabetes may contribute to CRC carcinogenesis and proliferation through inflammation and oxidative stress-driven signaling alterations. 6,8 Meta-analyses report associations between type 2 diabetes and increased risk of CRC, with risk ratios ranging from 1.2 to 1.4. [9][10][11][12] CRC shares many risk factors with diabetes, including low socioeconomic status (SES), Black race, obesity, and smoking.…”

Section: Introductionmentioning

confidence: 99%

Type 2 Diabetes and Colorectal Cancer Risk

Lawler,

Walts,

Steinwandel

et al. 2023

JAMA Netw Open

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ImportanceType 2 diabetes and colorectal cancer (CRC) disproportionately burden indviduals of low socioeconomic status and African American race. Although diabetes is an emerging CRC risk factor, associations between diabetes and CRC in these populations are understudied.ObjectiveTo determine if diabetes is associated with CRC risk in a cohort representing understudied populations.Design, Setting, and ParticipantsThis cohort study uses data from the prospective Southern Community Cohort Study in the US, which recruited from 2002 to 2009 and completed 3 follow-up surveys by 2018. Of about 85 000 participants, 86% enrolled at community health centers, while 14% were enrolled via mail or telephone from the same 12 recruitment states. Participants with less than 2 years of follow-up, previous cancer diagnosis (excluding nonmelanoma skin cancer) at enrollment, missing enrollment diabetes status, diabetes diagnosis before age 30, and without diabetes at enrollment with no follow-up participation were excluded. Data were analyzed from January to September 2023.ExposuresPhysician-diagnosed diabetes and age at diabetes diagnosis were self-reported via survey at enrollment and 3 follow-ups.Main Outcomes and MeasuresDiabetes diagnosis was hypothesized to be positively associated with CRC risk before analysis. Incident CRC was assessed via state cancer registry and National Death Index linkage. Hazard ratios and 95% CIs were obtained via Cox proportional hazard models, using time-varying diabetes exposure.ResultsAmong 54 597 participants, the median (IQR) enrollment age was 51 (46-58) years, 34 786 (64%) were female, 36 170 (66%) were African American, and 28 792 (53%) had income less than $15 000 per year. In total, 289 of 25 992 participants with diabetes developed CRC, vs 197 of 28 605 participants without diabetes. Diabetes was associated with increased CRC risk (hazard ratio [HR], 1.47; 95% CI, 1.21-1.79). Greater associations were observed among participants without colonoscopy screening (HR, 2.07; 95% CI, 1.16-3.67) and with smoking history (HR, 1.62; 95% CI, 1.14-2.31), potentially due to cancer screening differences. Greater associations were also observed for participants with recent diabetes diagnoses (diabetes duration &lt;5 years compared with 5-10 years; HR, 2.55; 95% CI, 1.77-3.67), possibly due to recent screening.Conclusions and RelevanceIn this study where the majority of participants were African American with low socioeconomic status, diabetes was associated with elevated CRC risk, suggesting that diabetes prevention and control may reduce CRC disparities. The association was attenuated for those who completed colonoscopies, highlighting how adverse effects of diabetes-related metabolic dysregulation may be disrupted by preventative screening.

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