Objectives: The consistently observed epidemiologic associations of obesity and physical activity with colorectal cancer and precursor adenoma risk suggest that insulin and glucose control may be contributory. We evaluated the association of glycosylated hemoglobin (HbA1c), a clinical indicator of average glycemia over the previous 2 months, and possibly, indirectly, a marker of average blood insulin level, with colorectal carcinogenesis.
Methods: Among women in the Nurses' Health Study, who provided blood in 1989-90 and were diagnosed subsequently in 1989-94, we included 79 colorectal cancer cases and 156 matched controls, and 201 distal colorectal adenoma cases and 201 matched controls. HbA1c concentrations in red blood cells were determined blindly by turbidometric immunoinhibition. Odds ratios (OR) and 95% confidence intervals (CI) were estimated from conditional logistic regression models.
Results: HbA1c level did not significantly differ between colorectal cancer cases (median 5.5%) and controls (5.5%, p = 0.5), although a small difference between adenoma cases (5.6%) and controls (5.5%, p = 0.06) was noted. Compared to the lowest tertile of HbA1c (median 5.2%), women in the middle (median 5.5%, OR = 1.2, CI = 0.6-2.5) and upper (5.8%, OR = 1.2, CI = 0.6-2.7) tertiles were not at an increased risk for colorectal cancer. A modestly elevated risk of distal colorectal adenoma in the upper (median 5.8%, OR = 1.4, CI = 0.9-2.3) versus lower (median 5.3%) tertile could not be excluded. These associations were not appreciably altered after adjusting for known and suspected colorectal cancer risk factors.
Conclusion: Over the range of levels observed in this relatively small sample of middle-aged women, prediagnostic HbA1c does not clearly predict colorectal cancer and adenoma risk.