Abstract
Previous studies have reported associations between diabetes and cancer risk. However, specific association of hemoglobin A1c (HbA1c) levels with cancer risk remains inconclusive. We followed 29,629 individuals (11,336 men; 18,293 women) aged 46-80 years who participated in the Japan Public Health Center-based prospective study who had HbA1c measurements available and were cancer-free at baseline. Cancer incidence was assessed by systemic surveys. We estimated hazard ratios (HRs) for cancer risk with adjustment for age sex, geographic area, body mass index, smoking status, physical activity, alcohol, coffee, vegetable and total energy consumption, and history of cardiovascular disease. After a median follow-up of 8.5 years, 1,955 individuals had developed cancer. Higher HbA1c levels within both the non-diabetic and diabetic ranges in individuals without known diabetes were associated with overall cancer risk. Compared with individuals without known diabetes and HbA1c levels of 5.0-5.4%, the HRs for all cancers were 1.27 (95% confidence interval, 1.07-1.52); 1.01 (0.90-1.14); 1.28 (1.09-1.49); and 1.43 (1.14-1.80) for individuals without known diabetes and HbA1c levels <5.0%, 5.5-5.9%, 6.0-6.4%, and ≥6.5%, respectively, and 1.23 (1.02-1.47) for individuals with known diabetes. The lowest HbA1c group had the highest risk of liver cancer, and HbA1c levels were linearly associated with the risk of all cancers after excluding liver cancer (P for linear trend, 0.004). In conclusion, our findings corroborate the notion that glycemic control in individuals with high HbA1c levels may be important not only to prevent diabetes but also to prevent cancer.