Journal
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION
Volume 22, Issue 10, Pages 1825-1836Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1055-9965.EPI-13-0330
Keywords
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Funding
- National Heart, Lung, and Blood Institute (NHLBI)
- Boston University [N01-HC-25195]
- Framingham Food Frequency Questionnaire [53-3k06-5-10, 58-1950-9-001, 58-1950-4-401, 58-1950-7-707]
- American Cancer Society Research Scholar Grant [RSG-12-005-01-CNE]
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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 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 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, 1.11.5). 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. (C) 2013 AACR.
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