Fowke Jay H, Chung Fung-Lung, Jin Fan, Qi Dai, Cai Qiuyin, Conaway Cliff, Cheng Jia-Rong, Shu Xiao-Ou, Gao Yu-Tang, Zheng Wei
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232-8300, USA.
Cancer Res. 2003 Jul 15;63(14):3980-6.
Brassica vegetable consumption (e.g., Chinese cabbage) provides isothiocyanates (ITC) and other glucosinolate derivatives capable of inducing Phase II enzymes [e.g., glutathione S-transferases (GSTM1, GSTT1, and GSTP1) and NADPH quinine oxidoreductase] and apoptosis, altering steroid hormone metabolism, regulating estrogen receptor response, and stabilizing cellular proliferation. Asian populations consuming large amounts of Brassica have a lower breast cancer incidence compared with Western populations; however, the association between Brassica consumption and breast cancer risk is uncertain. It is difficult to estimate glucosinolate exposure and degradation in humans, possibly limiting epidemiological investigations of Brassica and cancer associations. We conducted a case control investigation of breast cancer in Shanghai, China, using urinary ITC levels as a biological measure of glucosinolate intake and degradation in populations with habitual Brassica intake. A representative subgroup of 337 cases providing presurgery, fasting, and first-morning urine specimens was one-to-one matched (age, menopausal status, date of urine collection, and day of laboratory assay) to population controls. Urinary ITC levels were inversely associated with breast cancer [odds ratio (OR) (Quartile 1) = 1 (ref); OR(Q2) = 0.9, 95% confidence interval (0.6, 1.4); OR(Q3) = 0.7, (0.5, 1.1); OR(Q4) = 0.5, (0.3, 0.8), adjusted for age, menopausal status, soy protein, fibroadenoma history, family breast cancer, physical activity, waist-to-hip ratio, body mass index, age at menarche, and parity in conditional logistic model]. This protective association persisted within post and premenopausal women. In contrast, total Brassica intake estimated from a food frequency questionnaire was not associated with breast cancer. Trends in the association between urinary ITC and breast cancer were more consistent with homozygous deletion of GSTM1 or GSTT1, the AAgenotype of GSTP1 (A313G), or with the C allele of NADPH quinine oxidoreductase (C609T), although interactions were not statistically significant. In conclusion, greater Brassica vegetable consumption, as measured by the urinary ITC biomarker, was associated with significantly reduced breast cancer risk among Chinese women.
食用十字花科蔬菜（如大白菜）可提供异硫氰酸盐（ITC）和其他硫代葡萄糖苷衍生物，这些物质能够诱导II期酶[如谷胱甘肽S-转移酶（GSTM1、GSTT1和GSTP1）和NADPH醌氧化还原酶]并引发细胞凋亡，改变类固醇激素代谢，调节雌激素受体反应，并稳定细胞增殖。与西方人群相比，大量食用十字花科蔬菜的亚洲人群乳腺癌发病率较低；然而，食用十字花科蔬菜与乳腺癌风险之间的关联尚不确定。很难估计人体中硫代葡萄糖苷的暴露量和降解情况，这可能限制了对十字花科蔬菜与癌症关联的流行病学调查。我们在中国上海进行了一项乳腺癌病例对照研究，将尿ITC水平作为习惯性食用十字花科蔬菜人群中硫代葡萄糖苷摄入量和降解情况的生物学指标。337例提供术前、空腹和晨尿样本的代表性亚组病例与人群对照进行一对一匹配（年龄、绝经状态、尿液采集日期和实验室检测日期）。尿ITC水平与乳腺癌呈负相关[比值比（OR）（四分位数1）=1（参照）；OR（四分位数2）=0.9，95%置信区间（0.6，1.4）；OR（四分位数3）=0.7，（0.5，1.1）；OR（四分位数4）=0.5，（0.3，0.8），在条件逻辑模型中对年龄、绝经状态、大豆蛋白、纤维瘤病史、家族性乳腺癌、身体活动、腰臀比、体重指数、初潮年龄和产次进行了校正]。这种保护关联在绝经后和绝经前女性中均持续存在。相比之下，通过食物频率问卷估计的十字花科蔬菜总摄入量与乳腺癌无关。尿ITC与乳腺癌之间关联的趋势与GSTM1或GSTT1的纯合缺失、GSTP1（A313G）的AA基因型或NADPH醌氧化还原酶（C609T）的C等位基因更为一致，尽管相互作用无统计学意义。总之，以尿ITC生物标志物衡量，食用更多十字花科蔬菜与中国女性乳腺癌风险显著降低相关。
