Journal
ANNALS OF EPIDEMIOLOGY
Volume 25, Issue 4, Pages 263-269Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.annepidem.2015.01.009
Keywords
Breast cancer; Body mass index; Oxidative stress; DNA repair; Epidemiology
Categories
Funding
- Department of Defense [BC093608]
- National Cancer Institute
- National Institutes of Environmental Health and Sciences [UO1CA/ES66572, P30ES009089, P30ES10126, P50CA058223, R25CA057726]
Ask authors/readers for more resources
Purpose: Obesity is associated with increased bioavailability of estrogen, hyperinsulinemia, and chronic inflammation, all of which may promote tumor growth. Given DNA repair and oxidative stress pathways may work together with these mechanisms to influence carcinogenesis, we hypothesized that genetic variation in these pathways may modify the obesity-postmenopausal breast cancer (BC) association. Methods: Resources from a population-based case-control study (990 cases and 970 controls) were used to construct logistic regression models. Body mass index (BM!, weight [kilogram]/height [square meter)) was assessed 1 year before reference date. We characterized interactions between BMI and 29 genetic polymorphisms in oxidative stress and DNA repair pathways. Results: Age-adjusted odds ratios (95% confidence intervals) for postmenopausal BC were 1.24 (1.00-1.52) and 1.35 (1.09-1.71) for 25 > BMI <30 and BMI >= 30 kg/m(2), respectively. We observed multiplicative interactions (P <= .05) for eight gene polymorphisms in DNA repair and oxidative stress pathways. For example, among MPO variant allele carriers, obesity was associated with a twofold increased risk of postmenopausal BC (2.13 [1.35-3361); however, in wild-type homozygotes, the relationship was less pronounced (133 [0.93-1.89]). Our findings were no longer significant after Bonferroni correction. Conclusions: Obesity may be particularly deleterious for postmenopausal BC development in the presence of biologically plausible DNA repair or oxidative stress genotypes. (C) 2015 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available