Metabolic Dysregulation of the Insulin–Glucose Axis and Risk of Obesity-Related Cancers in the Framingham Heart Study-Offspring Cohort (1971–2008)
Menée de 1971 à 2008 auprès de 4 615 participants (âge moyen : 66,8 ans), cette étude de cohorte analyse l'association entre des dérèglements du métabolisme du glucose et le risque de cancer lié à l'obésité
Background: Obesity-related dysregulation of the insulin–glucose axis is hypothesized in carcinogenesis. We studied impaired fasting glucose (IFG) and other markers of insulin–glucose metabolism in the Framingham Heart Study-Offspring Cohort, which uniquely tracks these markers and cancer >37 years. Methods: Participants were recruited between 1971 and 1975 and followed until 2008 (n = 4,615; mean age 66.8 years in 2008). Serum glucose, insulin, and hemoglobin A1c were determined from fasting blood in quart-annual exams. Lifestyle and demographic information was self-reported. HRs and 95% confidence intervals (CI) of cancer risk were computed using time-dependent survival analysis (SASv9.3), while accounting for temporal changes for relevant variables. Results: We identified 787 obesity-related cancers, including 136 colorectal, 217 breast, and 219 prostate cancers. Absence versus presence of IFG 10 to 20 years and 20+ years before the event or last follow-up was associated with 44% (95% CI, 1.15–1.79) and 57% (95% CI, 1.17–2.11) increased risk of obesity-related cancers, respectively. When time-dependent variables were used, after adjusting for age, sex, smoking, alcohol, and body mass index, IFG was associated with a 27% increased risk of obesity-related cancer (HR = 1.27; CI, 1.1–1.5). Associations were stronger in smokers (HR = 1.41; CI, 1.13–1.76). Increased risk was noted among persons with higher insulin (HR = 1.47; CI, 1.15–1.88) and hemoglobin A1c (HR = 1.54; CI, 1.13–2.10) for the highest (≥5.73%) versus lowest (≤5.25%) category. A >2-fold increase in colorectal cancer risk was observed for all blood biomarkers of insulin–glucose metabolism, particularly with earlier IFG exposure. Nonsignificant increased risk of breast and prostate cancer was observed for blood biomarkers. Conclusions: Earlier IFG exposure (>10 years before) increased obesity-related cancer risk, particularly for colorectal cancer.Impact: Our study explicitly recognizes the importance of prolonged IFG exposure in identifying links between glucose dysregulation and obesity-related cancers. Cancer Epidemiol Biomarkers Prev; 22(10); 1–12. ©2013 AACR.