Identification of Factors Associated With Colorectal Cancer Risk and Survival

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. In this dissertation, we examined several factors possibly associated with CRC risk or survival among participants from the Nurses’ Health Study and the Health Professionals Follow-Up Study, using Cox proportional hazards models. Chapter 1 examined fructose and sucrose intake in relation to CRC risk and mortality. We followed 86,323 women and 46,380 men for up to 32 years and found that fructose and sucrose intake was not associated with CRC risk or mortality (all P for trend ≥ 0.22), though separate analyses by gender and tumor location suggested a trend toward a positive association of fructose and sucrose intake with risk of proximal colon cancer in men (P for trend = 0.05 and 0.06, respectively). Chapter 2 examined the influence of pre-existing diabetes on survival among 2,604 patients with non-metastatic CRC. Diabetes was not associated with overall survival during the first 5 years after CRC diagnosis. Beyond 5 years, patients with diabetes experienced elevated overall mortality, compared to those without diabetes. The hazard ratios (HRs) for death were 1.01 (95% confidence interval [CI], 0.78-1.32), 1.51 (95% CI, 1.07-2.13) and 2.58 (95% CI, 1.79-3.73) during 0-5, >5-10, and >10 years after CRC diagnosis, respectively. Regarding cause-specific mortality, patients with diabetes had increased mortality from non-CRC cancers (HR, 2.03; 95% CI, 1.28-3.23) and cardiovascular disease (HR, 1.98; 95% CI, 1.23-3.20). Chapter 3 examined the relationship between plasma vitamin D binding protein (VDBP), bioavailable or free 25-hydroxyvitamin D [25(OH)D], and CRC survival. Among 604 CRC patients with prediagnostic blood samples, higher VDBP levels were associated with a significant improvement in overall and CRC-specific survival (P for trend = 0.005 and 0.02, respectively). However, no association with overall or CRC-specific survival was observed for bioavailable or free 25(OH)D levels. In conclusion, we found little evidence for an association of fructose and sucrose intake with CRC risk or mortality. Diabetes was associated with increased long-term mortality among patients with non-metastatic CRC, especially mortality from non-CRC cancers and cardiovascular disease. Higher prediagnostic plasma VDBP levels were associated with increased overall and CRC-specific survival.