Diabetes mellitus in relation to colorectal tumor molecular subtypes: A pooled analysis of more than 9000 cases

Harlid, Sophia; Guelpen, Bethany Van; Qu, Conghui; Gylling, Björn; Aglago, Elom K.; Amitay, Efrat L.; Brenner, Hermann; Buchanan, Daniel D.; Campbell, Peter T.; Cao, Yin; Chan, Andrew T.; Chang‐Claude, Jenny; Drew, David A.; Figueiredo, Jane C.; French, Amy J.; Gallinger, Steven; Giannakis, Marios; Giles, Graham G.; Gunter, Marc J.; Hoffmeister, Michael; Hsu, Li; Jenkins, Mark A.; Lin, Yi; Murphy, Neil; Newcomb, Polly A.; Newton, Christina C.; Nowak, Jonathan A.; Obón-Santacana, Mireia; Ogino, Shuji; Potter, John D.; Song, Mingyang; Steinfelder, Robert S.; Sun, Wei; Thibodeau, Stephen N.; Toland, Amanda E.; Ugai, Tomotaka; Um, Caroline Y.; Woods, Michael O.; Phipps, Amanda I.; Harrison, Tabitha A.; Peters, Ulrike

doi:10.1002/ijc.34015

Cited by 4 publications

(1 citation statement)

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“…BRAF mutations, found in 8-12% of CRC cases, are usually associated with a poor prognosis. They tend to occur in proximal CC, in older patients, and often co-occur with high-level microsatellite instability [21]. Harlid et al (2022), in a pooled analysis including 9,756 CRC patients, confirmed that diabetes particularly increases the risk of BRAF-mutated tumors [21].…”

Section: Discussionmentioning

confidence: 84%

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer

Baleiras¹,

Domingues²,

Severino³

et al. 2023

Cureus

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BackgroundDiabetes mellitus (DM) is a prognostic factor for some malignancies, but its clinical implications in metastatic colorectal cancer (mCRC) patients are less clear. Therefore, we conducted a retrospective study to evaluate the impact of pre-existing type 2 diabetes mellitus (T2DM) on the survival outcomes of patients with newly diagnosed mCRC. MethodologyWe retrospectively included patients with newly diagnosed mCRC between January 2017 and June 2021 and with pre-existing T2DM. Data on the characteristics of patients, clinicopathological features, and drug exposure were collected from the electronic medical records. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival (PFS) and treatment-related adverse events (TRAEs). ResultsAmong 187 mCRC patients, 54 (28.8%) had T2DM. The median follow-up was 25 months. We observed 150 OS events and 168 PFS events. Diabetes significantly and negatively impacted PFS and OS. The median for PFS (mPFS) was eight and 16 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). The median overall survival (mOS) was 15 and 29 months for T2DM and no T2DM patients, respectively (p < 0.0001; log-rank test). Patients with diabetes were more often overweight or obese (59.3% vs. 24.8%; p < 0.01) and had a poorer performance status (53.7% vs. 21.1% with Eastern Cooperative Oncology Group Performance Status 1; p < 0.01). Additionally, T2DM patients had more high-risk pathological features, including G3 grading tumors (27.7% vs. 12.0%; p = 0.01), lymph node involvement (p < 0.01), BRAF-mutated (35.1% vs. 6.8%; p < 0.01), and right-sided CRC (63.0% vs. 30.1%; p < 0.01). We found no statistically significant differences in TRAEs. Nevertheless, a significantly higher rate of grade 2-4 peripheral neuropathy (22.2% vs. 5.3%; p < 0.01) was reported in T2DM patients. ConclusionsT2DM is a negative prognostic factor for survival in mCRC. The paper provides empirical evidence in favor of the joint control of both pathologies. Further research is needed to establish the robustness of our results.

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Section: Discussionmentioning

confidence: 84%

Prognostic Impact of Type 2 Diabetes in Metastatic Colorectal Cancer

Baleiras¹,

Domingues²,

Severino³

et al. 2023

Cureus

View full text Add to dashboard Cite

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Diabetes mellitus in relation to colorectal tumor molecular subtypes: A pooled analysis of more than 9000 cases

Harlid

Guelpen

et al. 2022

Intl Journal of Cancer

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Diabetes is an established risk factor for colorectal cancer. However, colorectal cancer is a heterogeneous disease and it is not well understood whether diabetes is more strongly associated with some tumor molecular subtypes than others. A better understanding of the association between diabetes and colorectal cancer according to molecular subtypes could provide important insights into the biology of this association. We used data on lifestyle and clinical characteristics from the Colorectal Cancer Family Registry (CCFR) and the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO), including 9756 colorectal cancer cases (with tumor marker data) and 9985 controls, to evaluate associations between reported diabetes and risk of colorectal cancer according to molecular subtypes. Tumor markers included BRAF and KRAS mutations, microsatellite instability and CpG island methylator phenotype.

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