Carcinogenesis Advance Access first published online on March 2, 2009
This version published online on March 17, 2009
Carcinogenesis, doi:10.1093/carcin/bgp053
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Oxidative Stress Related Genotypes, Fruit and Vegetable Consumption, and Breast Cancer Risk
1 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY 14263
2 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892
3 Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta GA 30329
Address request for reprints to: Chi-Chen Hong, PhD, Roswell Park Cancer Institute, Elm & Carlton Sts., Buffalo, NY 14263, Chi-Chen Hong{at}roswellpark.org, Tel: (716) 845-7785, Fax: (716) 845-5125
Dietary antioxidants may interact with endogenous sources of pro- and antioxidants to impact breast cancer risk. A nested case-control study of postmenopausal women (505 cases, 502 controls) from the Cancer Prevention Study-II Nutrition Cohort was conducted to examine the interaction between oxidative stress-related genes and level of vegetable and fruit intake on breast cancer risk. Genetic variations in CAT (C-262T), MPO (G-463A), NOS3 (G894T), and HO-1[(GT)n dinucleotide length polymorphism] were not associated with breast cancer risk. Women carrying the low risk CAT CC (OR = 0.75, 95% CI 0.50-1.11), NOS3 TT (OR = 0.54, 95% CI 0.26-1.12, p-trend = 0.10), or HO-1 S allele and MM genotype (OR = 0.56, 95% CI 0.37-0.55), however, were found to be at non-significantly reduced breast cancer risk among those with high vegetable and fruit intake (
median; p-interactions = 0.04 for CAT, p = 0.005 for NOS3, and p = 0.07 for HO-1). Furthermore, those with 4 putative low risk alleles in total had significantly reduced risk (OR = 0.53, 95% CI = 0.32-0.88, p-interaction = 0.006) compared to those with 
2 low risk alleles. In contrast, among women with low vegetable and fruit intake (< median), the low risk CAT CC (OR=1.33, 95% CI 0.89-1.99), NOS3 TT (OR=2.93, 1.38-6.22), and MPO AA (OR=2.09, 95% CI 0.73-5.95) genotypes appeared to be associated with raised breast cancer risk, with significantly increased risks observed in those with 4 low risk alleles compared to participants with 2 low risk alleles (OR: 1.77, 95% CI 1.05-2.99, p-interaction = 0.006). Our results support the hypothesis that there are joint effects of endogenous and exogenous antioxidants.
Key Words: Genetic polymorphisms • fruit and vegetable intake • breast cancer risk • oxidative stress • nested-case control study
Received September 11, 2008; revised January 26, 2009; accepted February 21, 2009.