Urinary isothiocyanate levels, brassica, and human breast cancer.
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.
Fowke
Jay H
JH
Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee 37232-8300, USA. jay.fowke@vanderbilt.edu
Chung
Fung-Lung
FL
Jin
Fan
F
Qi
Dai
D
Cai
Qiuyin
Q
Conaway
Cliff
C
Cheng
Jia-Rong
JR
Shu
Xiao-Ou
XO
Gao
Yu-Tang
YT
Zheng
Wei
W
D000328:Adult; D001937:Brassica / Q000378:metabolism*; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000652:urine*; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007527:Isoenzymes / Q000235:genetics; D017879:Isothiocyanates / Q000652:urine*; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics
D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; D017879:Isothiocyanates; D016660:NAD(P)H Dehydrogenase (Quinone); C037152:isothiocyanic acid; C447479:NQO1 protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human