Oxidative stress-related genotypes, fruit and vegetable consumption and breast cancer risk

Abstract

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) (C2262T), myeloperoxidase (MPO) (G2463A), 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) 5 0.75, 95% confidence interval (CI) 0.50-1.11], NOS3 TT (OR 5 0.54, 95% CI 5 0.26-1.12, P-trend 5 0.10) or HO-1 S allele and MM genotype (OR 5 0.56, 95% CI 5 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 5 0.04 for CAT, P 5 0.005 for NOS3 and P 5 0.07 for HO-1). Furthermore, those with ‡4 putative low-risk alleles in total had significantly reduced risk (OR 5 0.53, 95% CI 5 0.32-0.88, P-interaction 5 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 5 1.33, 95% CI 5 0.89-1.99), NOS3 TT (OR 5 2.93, 95% CI 5 1.38-6.22) and MPO AA (OR 5 2.09, 95% CI 5 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 5 1.77, 95% CI 5 1.05-2.99, P-interaction 5 0.006). Our results support the hypothesis that there are joint effects of endogenous and exogenous antioxidants.

Polymorphisms of the endothelial nitric oxide synthase gene in breast cancer: a genetic association study and meta-analysis

“…Nine articles were considered to be potentially eligible after the article review. [7][8][9][10][11][12][13][14][15] In one article, 7 the subjects overlapped with the subjects of the more recent and larger study by Li et al, 8 which was eventually included in the meta-analysis. In another article, 15 the data were not extractable.…”

“…In another article, 15 the data were not extractable. Seven articles [8][9][10][11][12][13][14] that investigated the association between any of the G894T, 4b/a and T786C polymorphisms and BC met the inclusion criteria. Genotypic information on NOS3 variants was not available (in publication tables or online appendices) from the eight GWAS conducted to date.…”

“…The articles were reviewed and data were extracted by two investigators (EZ and GK); disagreements were resolved after a discussion between the authors. Eight studies dealt with G894T (Zintzaras), [8][9][10][11][12][13][14] three with 4b/a (Zintzaras) 10,11 and three with T786C. 9,10,12 The studies that investigated 4b/a or T786C had also investigated G894T.…”

“…Among the tested variants of the NOS3 gene, a non-synonymous single-nucleotide polymorphism (G894T substitution in exon 7-rs1799983) and a variable number of tandem repeats in intron 4 (4b/a) have been commonly tested in association with BC, on the basis of their potential functional effects 6 and their relatively high minor allele frequency in various ethnic groups. [7][8][9][10][11][12][13][14][15] Candidate-gene studies have nevertheless a poor replication record, which has necessitated the use of stringent validation criteria. Inconsistent results have been also reported by previous studies on the NOS3 and BC association.…”

“…Inconsistent results have been also reported by previous studies on the NOS3 and BC association. [7][8][9][10][11][12][13][14][15] Furthermore, agnostic evidence generated by eight genome-wide association studies (GWASs) has not shown any role for NOS3 region variants. 16 Consequently, the status of associations for variants from candidate-gene studies remains equivocal.…”