Niyati Parekh1, Yong Lin, Maya Vadiveloo, Richard B Hayes, Grace L Lu-Yao. 1. Authors' Affiliations: Nutrition, Food Studies, and Public Health, Steinhardt School, New York University; Population Health, Langone School of Medicine, New York University, New York, New York; Biostatistics, School of Public Health, Rutgers University; Medicine, Rutgers University-Robert Wood Johnson Medical School, Piscataway; and Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.
Abstract
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.
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.
Authors: Esther K Wei; Jing Ma; Michael N Pollak; Nader Rifai; Charles S Fuchs; Susan E Hankinson; Edward Giovannucci Journal: Cancer Epidemiol Biomarkers Prev Date: 2005-04 Impact factor: 4.254
Authors: Kenneth C Johnson; Anthony B Miller; Neil E Collishaw; Julie R Palmer; S Katharine Hammond; Andrew G Salmon; Kenneth P Cantor; Mark D Miller; Norman F Boyd; John Millar; Fernand Turcotte Journal: Tob Control Date: 2010-12-08 Impact factor: 7.552
Authors: Juan F Ascaso; Susana Pardo; José T Real; Rosario I Lorente; Antonia Priego; Rafael Carmena Journal: Diabetes Care Date: 2003-12 Impact factor: 19.112
Authors: Nour Makarem; Elisa V Bandera; Yong Lin; Paul F Jacques; Richard B Hayes; Niyati Parekh Journal: Br J Nutr Date: 2017-06-29 Impact factor: 3.718
Authors: Niyati Parekh; Guia Guffanti; Yong Lin; Heather M Ochs-Balcom; Nour Makarem; Richard Hayes Journal: Cancer Causes Control Date: 2015-06-16 Impact factor: 2.506
Authors: Pradeep Natarajan; Nina B Gold; Alexander G Bick; Heather McLaughlin; Peter Kraft; Heidi L Rehm; Gina M Peloso; James G Wilson; Adolfo Correa; Jonathan G Seidman; Christine E Seidman; Sekar Kathiresan; Robert C Green Journal: Sci Transl Med Date: 2016-11-09 Impact factor: 17.956
Authors: Lynn L Moore; Susan Chadid; Martha R Singer; Bernard E Kreger; Gerald V Denis Journal: Cancer Epidemiol Biomarkers Prev Date: 2014-07-10 Impact factor: 4.254