Preliminary Communication: Glycated Hemoglobin, Diabetes, and Incident Colorectal Cancer in Men and Women: A Prospective Analysis from the European Prospective Investigation into Cancer–Norfolk Study

BACKGROUND: Increasing evidence suggests that abnormal glucose metabolism may be associated with increased risk of colorectal cancer. METHODS: We examined the relationship between known diabetes and glycated hemoglobin (HbA1c) concentrations measured in 1995 to 1997 and subsequent incident colorectal cancer after 6 years follow-up in 9,605 men and women ages 45 to 79 years in the European Prospective Investigation into Cancer-Norfolk Study. RESULTS: Among individuals not known to have cancer at the baseline survey, there were 67 incident colorectal cancers. HbA1c concentration appeared continuously related to incident colorectal cancer risk, with lowest rates observed in those with HbA1c below 5%. Known diabetes was also associated with incident colorectal cancer, with relative risk (RR) 3.18 and 95% confidence interval (CI) 1.36-7.40 (P < 0.01) adjusting for age and sex and RR 2.78 and 95% CI 1.10-7.00 (P = 0.03) adjusting for age, sex, body mass index, and smoking compared with those without known diabetes. The RR (95% CI) of incident colorectal cancer per 1% absolute increase in HbA1c was 1.34 (1.12-1.59; P < 0.001). HbA1c concentrations appeared to explain the increased colorectal cancer risk associated with diabetes in multivariate models. CONCLUSIONS: Known diabetes was associated with approximately 3-fold risk of colorectal cancer in this analysis; this increased risk was largely explained by HbA1c concentrations, which appears continuously related to colorectal cancer risk across the population distribution.