Li Yulin, Ambrosone Christine B, McCullough Marjorie J, Ahn Jiyoung, Stevens Victoria L, Thun Michael J, Hong Chi-Chen
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Carcinogenesis. 2009 May;30(5):777-84. doi: 10.1093/carcin/bgp053. Epub 2009 Mar 2.
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.
膳食抗氧化剂可能与内源性促氧化剂和抗氧化剂相互作用，从而影响乳腺癌风险。我们对癌症预防研究-II营养队列中的绝经后女性（505例病例和502例对照）进行了一项巢式病例对照研究，以检验氧化应激相关基因与蔬菜和水果摄入量对乳腺癌风险的相互作用。过氧化氢酶（CAT）（C-262T）、髓过氧化物酶（MPO）（G-463A）、内皮型一氧化氮合酶（NOS3）（G894T）和血红素加氧酶-1（HO-1）[（GT）（n）二核苷酸长度多态性]的基因变异与乳腺癌风险无关。然而，在蔬菜和水果摄入量高（≥中位数）的女性中，携带低风险CAT CC[比值比（OR）=0.75，95%置信区间（CI）0.50-1.11]、NOS3 TT（OR = 0.54，95%CI = 0.26-1.12，P趋势=0.10）或HO-1 S等位基因和MM基因型（OR = 0.56，95%CI = 0.37-0.55）的女性患乳腺癌的风险有非显著降低（CAT的P相互作用=0.04，NOS3的P = 0.005，HO-1的P = 0.07）。此外，与携带≤2个低风险等位基因的女性相比，总共携带≥4个假定低风险等位基因的女性风险显著降低（OR = 0.53，95%CI = 0.32-0.88，P相互作用=0.006）。相反，在蔬菜和水果摄入量低（<中位数）的女性中，低风险CAT CC（OR = 1.33，95%CI = 0.89-1.99）、NOS3 TT（OR = 2.93，95%CI = 1.38-6.22）和MPO AA（OR = 2.09，95%CI = 0.73-5.95）基因型似乎与乳腺癌风险升高有关，与携带≤2个低风险等位基因的参与者相比，携带≥4个低风险等位基因的女性风险显著增加（OR = 1.77，95%CI = 1.05-2.99，P相互作用=0.006）。我们的结果支持内源性和外源性抗氧化剂存在联合作用的假设。
