Risk factors for cancer-related distress in colorectal cancer survivors: one year post surgery.

PURPOSES: Cancer-related distress is known to persist long after completion of treatment. Factors related to distress are largely unexplored in colorectal cancer (CRC) survivors. We examined changes over time and risk factors for distress in CRC patients over the first year after surgery. METHODS: We included 212 CRC patients with data at 6 and 12 months post-surgery from the ColoCare Study in Heidelberg, Germany. Sociodemographic and lifestyle factors, social support, and health-related quality of life (HrQOL) prior to surgery were evaluated as predictors of cancer-related distress. Distress was measured with the Cancer and Treatment Distress instrument (CTXD). Linear regression analyses examined associations between risk factors and distress. RESULTS: Distress subscale scores varied significantly over time: health burden subscale score increased (P < .001), while finances (P = .004), medical demands (P < .001), and identity (P < .001) subscale scores decreased over time. Uncertainty and family strain subscale scores did not change. Younger age, lower income, advanced tumor stage, poorer social support, and poorer baseline HrQOL predicted higher level distress at 6 and 12 months. CONCLUSION: Cancer-related distress continues unresolved after surgery. Although some risk factors are difficult to alter, those at highest risk can be identified earlier for possible preventive strategies. IMPLICATIONS FOR CANCER SURVIVORS: Screening for risk factors pre-surgery would allow for targeted interventions including strategies to improve resources for those with low support, thereby reducing long-term distress in CRC survivors.

Expression Patterns of Xenobiotic-Metabolizing Enzymes in Tumor and Adjacent Normal Mucosa Tissues among Patients with Colorectal Cancer: The ColoCare Study.

BACKGROUND: Xenobiotic-metabolizing enzymes (XME) play a critical role in the activation and detoxification of several carcinogens. However, the role of XMEs in colorectal carcinogenesis is unclear. METHODS: We investigated the expression of XMEs in human colorectal tissues among patients with stage I-IV colorectal cancer (n = 71) from the ColoCare Study. Transcriptomic profiling using paired colorectal tumor and adjacent normal mucosa tissues of XMEs (GSTM1, GSTA1, UGT1A8, UGT1A10, CYP3A4, CYP2C9, GSTP1, and CYP2W1) by RNA microarray was compared using Wilcoxon rank-sum tests. We assessed associations between clinicopathologic, dietary, and lifestyle factors and XME expression with linear regression models. RESULTS: GSTM1, GSTA1, UGT1A8, UGT1A10, and CYP3A4 were all statistically significantly downregulated in colorectal tumor relative to normal mucosa tissues (all P ≤ 0.03). Women had significantly higher expression of GSTM1 in normal tissues compared with men (ß = 0.37, P = 0.02). By tumor site, CYP2C9 expression was lower in normal mucosa among patients with rectal cancer versus colon cancer cases (ß = -0.21, P = 0.0005). Smokers demonstrated higher CYP2C9 expression levels in normal mucosa (ß = 0.17, P = 0.02) when compared with nonsmokers. Individuals who used NSAIDs had higher GSTP1 tumor expression compared with non-NSAID users (ß = 0.17, P = 0.03). Higher consumption of cooked vegetables (>1×/week) was associated with higher CYP3A4 expression in colorectal tumor tissues (ß = 0.14, P = 0.007). CONCLUSIONS: XMEs have lower expression in colorectal tumor relative to normal mucosa tissues and may modify colorectal carcinogenesis via associations with clinicopathologic, lifestyle, and dietary factors. IMPACT: Better understanding into the role of drug-metabolizing enzymes in colorectal cancer may reveal biological differences that contribute to cancer development, as well as treatment response, leading to clinical implications in colorectal cancer prevention and management.

Circulating Folate and Folic Acid Concentrations: Associations With Colorectal Cancer Recurrence and Survival.

BACKGROUND: Folates, including folic acid, may play a dual role in colorectal cancer development. Folate is suggested to be protective in early carcinogenesis but could accelerate growth of premalignant lesions or micrometastases. Whether circulating concentrations of folate and folic acid, measured around time of diagnosis, are associated with recurrence and survival in colorectal cancer patients is largely unknown. METHODS: Circulating concentrations of folate, folic acid, and folate catabolites p-aminobenzoylglutamate and p-acetamidobenzoylglutamate were measured by liquid chromatography-tandem mass spectrometry at diagnosis in 2024 stage I-III colorectal cancer patients from European and US patient cohort studies. Multivariable-adjusted Cox proportional hazard models were used to assess associations between folate, folic acid, and folate catabolites concentrations with recurrence, overall survival, and disease-free survival. RESULTS: No statistically significant associations were observed between folate, p-aminobenzoylglutamate, and p-acetamidobenzoylglutamate concentrations and recurrence, overall survival, and disease-free survival, with hazard ratios ranging from 0.92 to 1.16. The detection of folic acid in the circulation (yes or no) was not associated with any outcome. However, among patients with detectable folic acid concentrations (n = 296), a higher risk of recurrence was observed for each twofold increase in folic acid (hazard ratio = 1.31, 95% confidence interval = 1.02 to 1.58). No statistically significant associations were found between folic acid concentrations and overall and disease-free survival. CONCLUSIONS: Circulating folate and folate catabolite concentrations at colorectal cancer diagnosis were not associated with recurrence and survival. However, caution is warranted for high blood concentrations of folic acid because they may increase the risk of colorectal cancer recurrence.

Body Fatness, Adipose Tissue Compartments, and Biomarkers of Inflammation and Angiogenesis in Colorectal Cancer: The ColoCare Study.

BACKGROUND: Adiposity has been linked to both risk and prognosis of colorectal cancer; however, the impact of different fat areas [visceral (VFA) vs. subcutaneous fat area (SFA)] is unclear. We investigated associations between adiposity and biomarkers of inflammation and angiogenesis among patients with colorectal cancer. METHODS: Preoperative serum samples and computed tomography scans were obtained from 188 patients diagnosed with primary invasive stage I-IV colorectal cancer enrolled in the ColoCare Study. Adiposity was assessed by area-based quantification of VFA, SFA, and VFA:SFA ratio on spinal levels L3/L4 and L4/L5. Circulating levels of inflammation (CRP, SAA, sICAM-1, and sVCAM-1) and angiogenesis (VEGF-A and VEGF-D) were assessed from patient sera on the Meso Scale Discovery platform. Partial correlations and regression analyses, adjusted for age, sex, and tumor stage, were performed. RESULTS: VFA was moderately correlated with CRP and SAA (CRP: L3/L4 and L4/L5:r = 0.21, P = 0.01; SAA: L3/L4:r = 0.17, P = 0.04). The correlation between SFA and the measured biomarkers were weak (r ≤ 0.13, not significant). The ratio of VFA:SFA at L3/L4 was moderately correlated with VEGF-A (r = 0.28, P = 0.0008) and SAA (r = 0.24, P = 0.006), and less so with CRP (r = 0.18, P = 0.04) and sICAM-1 (r = 0.18, P = 0.04). Similar correlations were found for the VFA:SFA ratio at L4/L5. CONCLUSIONS: We observed an association between visceral adiposity and biomarkers of inflammation and angiogenesis in colorectal cancer. In particular, the VFA:SFA ratio was correlated with circulating levels of the proangiogenic biomarker VEGF-A. IMPACT: Our findings support a direct association of visceral adipose tissue with inflammatory and angiogenic processes, which play fundamental roles in the development and progression of colorectal cancer.