Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk.
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 (> or = median; P-interactions = 0.04 for CAT, P = 0.005 for NOS3 and P = 0.07 for HO-1). Furthermore, those with > or = 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 < or = 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 > or = 4 low-risk alleles compared with participants with < or = 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.
Li
Yulin
Y
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Ambrosone
Christine B
CB
McCullough
Marjorie J
MJ
Ahn
Jiyoung
J
Stevens
Victoria L
VL
Thun
Michael J
MJ
Hong
Chi-Chen
CC
D000975:Antioxidants / Q000008:administration & dosage; D001943:Breast Neoplasms / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D002374:Catalase / Q000235:genetics; D015331:Cohort Studies; D004032:Diet; D005260:Female; D005638:Fruit; D005838:Genotype; D051547:Heme Oxygenase-1 / Q000235:genetics; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014675:Vegetables
D000975:Antioxidants; D002374:Catalase; D009195:Peroxidase; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D051547:Heme Oxygenase-1