Metabolic Dysregulation of the Insulin-Glucose Axis and Risk of Obesity-Related Cancers in the Framingham Heart Study - Offspring Cohort (1971-2008).pdfCancer Epidemiology, Biomarkers & Prevention (2013)
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 ¼ 4,615; mean age
66.8 years in 2008). Serum glucose, insulin, and hemoglobin A1c were determined from fasting blood in quartannual 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 20þ 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 ¼ 1.27; CI, 1.1–1.5). Associations were stronger in smokers (HR¼1.41; CI, 1.13–1.76). Increased risk was noted among persons with higher insulin (HR ¼ 1.47; CI, 1.15–1.88) and hemoglobin A1c (HR ¼ 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
Impact: Our study explicitly recognizes the importance of prolonged IFG exposure in identifying links between glucose dysregulation and obesity-related cancers.
Citation InformationNiyati Parekh, Yong Lin, Maya Vadiveloo, Richard B Hayes, et al.. "Metabolic Dysregulation of the Insulin-Glucose Axis and Risk of Obesity-Related Cancers in the Framingham Heart Study - Offspring Cohort (1971-2008).pdf" Cancer Epidemiology, Biomarkers & Prevention Vol. 22 Iss. 10 (2013) p. 1825 - 1836 ISSN: 1538-7755
Available at: http://works.bepress.com/maya-vadiveloo/14/