In a German population–based, matched case-control study reported in the Journal of Clinical Oncology, Wankhede et al found that type 2 diabetes (T2D) may be associated with colorectal cancer (CRC) risk and survival according to tumor immunity status.
Study Details
The study included 1,889 CRC cases without T2D and 473 cases with T2D as well as 2,012 controls without and 350 with T2D. Median follow-up of the CRC cases was 9.5 years. Tumor immune status was defined as the tumor immune cell score (ICS) derived from CD31 and CD81 T-cell densities measured at the invasive margin and tumor core of resected specimens. ICS was stratified into high (ICSHi), intermediate (ICSInt), and low (ICSLow) immune infiltration on the basis of standard cutoffs of 25% and 70%.
Key Findings
The association between T2D and CRC risk differed significantly by ICS (P for heterogeneity = .02). Odds ratios for the association were 1.39 (95% confidence interval [CI] = 1.17–1.66) overall, 1.80 (95% CI = 1.35–2.39) for ICSLow CRC subtype, and 1.42 (95% CI = 1.17–1.66) for ICSInt subtype; the odds ratio was not significant for ICSHi subtype (odds ratio = 1.16, 95% CI = 0.88–1.52).
Patients with T2D with ICSLow subtype had lower CRC-specific survival (hazard ratio [HR] = 1.99, 95% CI = 1.30–3.05) and disease-free survival (HR = 1.53, 95% CI = 1.05–2.26) vs patients without T2D, but no significant associations between CRC-specific survival or disease-free survival were observed for ICSInt and ICSHi subtypes.
Patients with T2D had increased risk of all-cause mortality and noncancer-related mortality across ICS subtypes. The strongest associations were with ICSLow subtype for all-cause mortality (adjusted HR = 1.70, 95% CI = 1.27–2.28) and with ICSLow subtype for noncancer-related mortality (adjusted HR = 2.24, 95% CI = 1.34–3.74).
The investigators concluded: “T2D disproportionately affects CRC risk and survival in tumors with low immune infiltration, suggesting a continuum of T2D’s impact from tumorigenesis to prognosis, through systemic and tumor-specific immune modulation. These findings highlight the need for precision prevention strategies integrating metabolic and immune-based interventions to mitigate CRC burden in patients with T2D.”
Michael Hoffmeister, PhD, of the Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Heidelberg, is the corresponding author of the Journal of Clinical Oncology article.
Disclosure: The study was supported by the German Research Council, Interdisciplinary Research Program of the National Center for Tumor Diseases, and German Federal Ministry of Education and Research. For full disclosures of all study authors, visit ascopubs.org.
