Catherine Duggan1, Richard N Baumgartner2, Kathy B Baumgartner2, Leslie Bernstein3, Stephanie George4, Rachel Ballard4, Marian L Neuhouser5, Anne McTiernan5,6. 1. Epidemiology Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. cduggan@fhcrc.org. 2. Department of Epidemiology & Population Health, University of Louisville, Louisville, KY, USA. 3. Department of Population Sciences, Beckman Research Institute, City of Hope, Duarte, CA, USA. 4. Office of Disease Prevention, National Institutes of Health, Rockville, MD, USA. 5. Epidemiology Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. 6. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA.
Abstract
PURPOSE: Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between polymorphisms in these genes and mortality in breast cancer survivors. METHODS: We investigated associations between TNF-α -308G > A (rs1800629); PPARγ Pro12Ala (rs1801282); and IRS-1 Gly972Arg (rs1801278) polymorphisms and anthropometric variables, circulating levels of previously measured biomarkers, and tumor characteristics in 553 women enrolled in the Health, Eating, Activity, and Lifestyle Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer between 1995 and 1999 (median follow-up 14.7 years). Using Cox proportional hazards models adjusted for possible confounders, we evaluated associations between these polymorphisms and mortality. RESULTS: Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only). There were no associations between any of the polymorphisms and tumor characteristics. Among 141 deaths, 62 were due to breast cancer. Carriers of the TNF-α-variant A allele had a decreased risk of breast-cancer-specific mortality [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.10-0.83] and all-cause mortality (HR 0.51; 95% CI 0.28-0.91). CONCLUSIONS: Neither the PPARγ nor the IRS-1 polymorphism was associated with mortality outcome. The TNF-α -308 G > A polymorphism was associated with reduced breast-cancer-specific and all-cause mortality.
PURPOSE:Tumor necrosis factor-α (TNF-α), peroxisome proliferator-activated receptor-γ (PPARγ), and insulin receptor substrate-1 (IRS-1) are associated with obesity, insulin resistance, and inflammation. Few data exist on associations between polymorphisms in these genes and mortality in breast cancer survivors. METHODS: We investigated associations between TNF-α -308G > A (rs1800629); PPARγ Pro12Ala (rs1801282); and IRS-1Gly972Arg (rs1801278) polymorphisms and anthropometric variables, circulating levels of previously measured biomarkers, and tumor characteristics in 553 women enrolled in the Health, Eating, Activity, and Lifestyle Study, a multiethnic, prospective cohort study of women diagnosed with stage I-IIIA breast cancer between 1995 and 1999 (median follow-up 14.7 years). Using Cox proportional hazards models adjusted for possible confounders, we evaluated associations between these polymorphisms and mortality. RESULTS: Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only). There were no associations between any of the polymorphisms and tumor characteristics. Among 141 deaths, 62 were due to breast cancer. Carriers of the TNF-α-variant A allele had a decreased risk of breast-cancer-specific mortality [hazard ratio (HR) 0.30; 95% confidence interval (CI) 0.10-0.83] and all-cause mortality (HR 0.51; 95% CI 0.28-0.91). CONCLUSIONS: Neither the PPARγ nor the IRS-1 polymorphism was associated with mortality outcome. The TNF-α -308 G > A polymorphism was associated with reduced breast-cancer-specific and all-cause mortality.
Authors: Jose C Florez; Marketa Sjögren; Noël Burtt; Marju Orho-Melander; Steve Schayer; Maria Sun; Peter Almgren; Ulf Lindblad; Tiinamaija Tuomi; Daniel Gaudet; Thomas J Hudson; Mark J Daly; Kristin G Ardlie; Joel N Hirschhorn; David Altshuler; Leif Groop Journal: Diabetes Date: 2004-12 Impact factor: 9.461
Authors: Hebe N Gouda; Gurdeep S Sagoo; Anne-Helen Harding; Jan Yates; Manjinder S Sandhu; Julian P T Higgins Journal: Am J Epidemiol Date: 2010-02-23 Impact factor: 4.897
Authors: John S Welch; Mercedes Ricote; Taro E Akiyama; Frank J Gonzalez; Christopher K Glass Journal: Proc Natl Acad Sci U S A Date: 2003-05-09 Impact factor: 11.205
Authors: Lisa Gallicchio; Howard H Chang; Dana K Christo; Lucy Thuita; Han Yao Huang; Paul Strickland; Ingo Ruczinski; Sandra Clipp; Kathy J Helzlsouer Journal: BMC Med Genet Date: 2009-10-09 Impact factor: 2.103