Carcinogenesis Advance Access originally published online on March 2, 2009
Carcinogenesis 2009 30(5):777-784; doi:10.1093/carcin/bgp053
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Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
1 Department of Epidemiology and Surveillance Research, American Cancer Society, Atlanta, GA 30329, USA
2 Nutritional Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
* To whom correspondence should be addressed. Tel: +1 716 845 7785; Fax: +1 716 845 8125; Email: Chi-Chen.Hong{at}RoswellPark.org
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 and 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 catalase (CAT) (C–262T), myeloperoxidase (MPO) (G–463A), endothelial nitric oxide synthase (NOS3) (G894T) and heme oxygenase-1 (HO-1) [(GT)n dinucleotide length polymorphism] were not associated with breast cancer risk. Women carrying the low-risk CAT CC [odds ratio (OR) = 0.75, 95% confidence interval (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 with 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, 95% CI = 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 with 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.
Abbreviations: BMI, body mass index; CAT, catalase; CPS, Cancer Prevention Study; DHEAS, dehydroepiandrosterone sulfate; FFQ, food frequency questionnaire; HO-1, heme oxygenase-1; LIBCSP, Long Island Breast Cancer Study Project; MAP, mitogen-activated protein; MPO, myeloperoxidase; NO, nitric oxide; NOS3, endothelial nitric oxide synthase; PI3K, phosphatidylinositol-3-kinase; ROS, reactive oxygen species; SNP, single nucleotide polymorphism; SP1, specificity protein 1
Received September 11, 2008; revised January 26, 2009; accepted February 21, 2009.