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BACKGROUND - Soy food intake may have protective effects against the risk for breast cancer, including estrogen receptor (ER)-negative breast cancer. However, the underlying molecular mechanisms remain unclear.
METHODS - To evaluate the association of soy intake with the expression of microRNAs (miRNAs) and genes in the tumor tissue of patients with triple-negative breast cancer (TNBC; ie, breast cancer lacking expression of ER, progesterone receptor, and human epidermal growth factor receptor 2), the expression of 800 miRNAs and 302 genes were measured with NanoString nCounter assays in formalin-fixed, paraffin-embedded tumor tissue from 272 TNBC patients. Soy intake during the 1-year period before the cancer diagnosis was assessed with a validated food-frequency questionnaire. The association of soy intake with the expression of miRNAs and genes was evaluated via linear regression analysis with adjustments for patient age and TNM stage.
RESULTS - A total of 14 miRNAs and 24 genes were significantly associated with soy food intake (P < .05): Thirteen of the 14 miRNAs (92.9%) and 9 of the 24 genes (37.5%), including tumor suppressors miR-29a-3p and IGF1R, showed overexpression for those women with high soy intake, whereas the remaining miRNAs and genes, including oncogenes KRAS and FGFR4, showed underexpression. Furthermore, cell growth-related genes showed a predominantly underexpression pattern according to a comparison of tumor samples from women with high soy food intake and samples from women with lower soy food intake.
CONCLUSIONS - This study suggests that long-term prediagnosis soy intake may lead to increased expression of tumor suppressors and decreased expression of oncogenes, especially cell growth-related genes, in breast tumor tissues. Cancer 2016;122:2544-51. © 2016 American Cancer Society.
© 2016 American Cancer Society.
Soy food intake has previously been associated with reduced breast cancer risk. Epidemiological evidence for subgroups of breast cancer, particularly by menopausal and hormone receptor status, is less consistent. To evaluate the role of hormone receptor and menopausal status on the association between soy food intake and breast cancer risk, we measured usual soy food intake in adolescence and adulthood via food frequency questionnaire in 70,578 Chinese women, aged 40-70 years, recruited to the Shanghai Women's Health Study (1996-2000). After a median follow-up of 13.2 years (range: 0.01-15.0), 1,034 incident breast cancer cases were identified. Using Cox models, we found that adult soy intake was inversely associated with breast cancer risk [hazard ratio (HR) for fifth versus first quintile soy protein intake = 0.78; 95% confidence interval (CI):0.63-0.97]. The association was predominantly seen in premenopausal women (HR = 0.46; 95% CI:0.29-0.74). Analyses further stratified by hormone receptor status showed that adult soy intake was associated with significantly decreased risk of estrogen receptor (ER)+/progesterone receptor (PR)+ breast cancer in postmenopausal women (HR = 0.72; 95% CI:0.53-0.96) and decreased risk of ER-/PR- breast cancer in premenopausal women (HR = 0.46; 95% CI:0.22-0.97). The soy association did not vary by human epidermal growth factor-2 (HER2) status. Furthermore, we found that high soy intake during adulthood and adolescence was associated with reduced premenopausal breast cancer risk (HR = 0.53; 95% CI: 0.32-0.88; comparing third vs. first tertile) while high adulthood soy intake was associated with postmenopausal breast cancer only when adolescent intake was low (HR = 0.63; 95% CI: 0.43-0.91). Our study suggests that hormonal status, menopausal status and time window of exposure are important factors influencing the soy-breast cancer association.
© 2016 UICC.
BACKGROUND - Choline deficiency has been shown to induce liver fat accumulation in both rodent and human studies. However, it is unclear whether dietary choline intake is related to fatty liver in the general population.
OBJECTIVE - We examined the association between choline intake and nonalcoholic fatty liver.
METHODS - Participants included 56,195 Chinese women and men, 40-75 y of age, with no or negligible alcohol consumption and with no history of hepatitis, cardiovascular disease, or cancer. All participants reported undergoing liver ultrasonography. Fatty liver was defined by self-report of a physician diagnosis. Habitual dietary intakes were assessed via validated food-frequency questionnaires.
RESULTS - The average total choline intakes were 289 ± 85 mg/d in women and 318 ± 92 mg/d in men. Major food sources were eggs, soy foods, red meat, fish, and vegetables. A higher choline intake was associated with lower risk of fatty liver; after adjustment for sociodemographic characteristics, lifestyle factors, and other dietary intakes, the ORs (95% CIs) for the highest vs. the lowest quintiles of choline intake were 0.68 (0.59, 0.79) in women and 0.75 (0.60, 0.93) in men (both P-trend < 0.01). The inverse association was attenuated after further adjustment for history of metabolic disease and, in particular, BMI. The corresponding ORs (95% CIs) were 0.88 (0.75, 1.03) in women (P-trend = 0.05) and 0.85 (0.68, 1.06) in men (P-trend = 0.09). Stratified analyses suggested a potential effect modification by obesity status in women; the OR (95% CI) across extreme quintiles was 0.72 (0.57, 0.91) in normal-weight women vs. 1.05 (0.84, 1.31) in overweight or obese women (P-trend = 0.007 vs. 0.99, P-interaction < 0.0001).
CONCLUSION - Higher dietary choline intake may be associated with lower risk of nonalcoholic fatty liver only in normal-weight Chinese women.
© 2014 American Society for Nutrition.
BACKGROUND AND AIMS - Consumption of foods that modulate inflammatory stress in genetically-prone individuals may influence development of cardiometabolic diseases. Isoflavones in soy-derived foods function as phytoestrogens, have antioxidant and anti-inflammatory activity, inhibit protein-tyrosine kinase activity, and may be atheroprotective. We examined the relationship between soy food consumption and inflammatory responses to endotoxemia, postprandial responses to oral lipid tolerance test (OLTT), and insulin sensitivity from frequently sampled intravenous tolerance tests (FSIGTT).
METHODS AND RESULTS - We administered low-dose endotoxin (LPS 1 ng/kg) to induce transient endotoxemia in young, healthy volunteers (N = 215) of African (AA), and European (EA) ancestry as part of the GENE Study. We further supported these findings in two independent samples: the MECHE Study and NHANES. Soy food consumption was a significant predictor of peak cytokine response following LPS. Individuals with moderate-high (>1.48 mg/day, N = 65) vs. low-no (<1.48 mg/day, N = 150) isoflavone consumption had significantly higher tumor necrosis factor alpha (TNFα) post-LPS (AUC, P = 0.009). Further, high-isoflavone consumers were protected against inflammation-induced decline in insulin sensitivity (SI) in GENE. We observed significant differences by soy consumption in the interferon gamma (IFNγ) response to OLTT, and the insulin response to OGTT in MECHE, as well as significantly lower fasting insulin, and 2-hour glucose post-OGTT in EA NHANES subjects.
CONCLUSION - We demonstrate that soy consumption may influence inflammatory and metabolic responses. In research of nutritional exposures, measuring evoked phenotypes may be more informative than describing resting characteristics. The GENE Study was registered under NCT00953667 and the MECHE Study under NCT01172951, both at clinicaltrials.gov.
Copyright © 2014 Elsevier B.V. All rights reserved.
Because the association between soy consumption and gastric cancer is inconsistent, we evaluated the putative preventive effect of soy food on gastric cancer risk in the Shanghai Women's and Men's Health Studies, comprising a total of 128,687 participants. Intake of nonfermented soy foods was estimated using 2 validated food-frequency questionnaires. HRs were calculated with 95% CIs for intake amounts of total nonfermented soy food intake, soy protein, and isoflavones as well as individual soy food groups using Cox proportional hazards regression. A total of 493 distal gastric cancer cases were identified by 2010. Although all risk estimates for summary measures of soy food intake above the lowest quartile (quartile 1) were suggestive of a protective effect, no statistically significant associations with risk of distal gastric cancer were found. Among the separate soy food groups, significant reductions in risk of distal gastric cancer by increasing intake of tofu were found in men in quartile 2 (HR: 0.59; 95% CI: 0.40, 0.86), quartile 3 (HR: 0.62; 95% CI: 0.44, 0.88), and quartile 4 (HR: 0.64; 95% CI: 0.42, 0.99), resulting in a significant trend (P-trend = 0.02). Dry bean intake was also inversely associated with decreased risk of gastric cancer, but in postmenopausal women only [quartile 2 (HR: 0.54; 95% CI: 0.30, 0.96); quartile 3 (HR: 0.90; 95% CI: 0.64, 1.27); and quartile 4 (HR: 0.63; 95% CI: 0.43, 0.91)], resulting in a significant trend (P-trend = 0.03). Overall, our study found no statistically significant association between nonfermented soy food intake and distal gastric cancer risk, though the data supported the hypothesis that tofu may protect against distal gastric cancer in men and dry bean consumption may decrease the risk of gastric cancer in postmenopausal women.
A published meta-analysis pooled individual studies by using the study-specific odds ratio (OR) or relative risk (RR) for the highest vs. lowest category of soy or isoflavone intake from each study, but it should be problematic to make comparison between studies/populations for lung cancer risk as the quantiles are so different from different studies/populations. Therefore, we conducted a meta-analysis to explore the association between exposure of estimated daily soy protein intake in grams and lung cancer risk. We extracted ORs or RRs and 95% confidence intervals (CIs), converted them to the estimated ones for daily soy protein intake and pooled them using fixed or random effects models from 11 epidemiologic studies. Overall, the inverse association between daily grams of soy protein intake and risk of lung cancer was borderline statistically significant (OR = 0.98, 95% CI = 0.96 to 1.00); the inverse association was statistically significant in nonsmokers (OR = 0.96; 95% CI = 0.93 to 0.99) and stronger than in smokers (P for difference <0.05). No statistical significance for the associations was observed between genders, the origin of the participants, study design and types of soy intake. This study suggests a borderline reduction in risk of lung cancer with daily soy protein intake in grams, and a significant inverse association in nonsmokers.
PURPOSE - We recently reported an inverse association between soy food intake and lung cancer risk among nonsmoking women. The effect size for aggressive lung cancers was larger than that observed for other types of lung cancer. Therefore, we hypothesized that soy consumption may favorably affect the overall survival of patients with lung cancer.
PATIENTS AND METHODS - This analysis included 444 women with incident lung cancer identified from the Shanghai Women's Health Study. Prediagnosis soy food intake was assessed at enrollment and reassessed 2 years later. Proportional hazards models were used to evaluate the association between soy food intake and overall survival.
RESULTS - Of the 444 patients with lung cancer, 318 died during follow-up. Initial analyses including all patients showed that higher intake of soy food was associated with better overall survival after adjusting for demographic and lifestyle characteristics and other nonclinical factors. Larger effect sizes for the association were found after additional adjustment for tumor stage and treatment in analyses including 301 patients with data available on these clinical factors. Compared with the median intake of soy food, fully adjusted hazard ratios for total mortality associated with the 10th, 30th, 70th, and 90th percentiles of intake were 1.81 (95% CI, 1.26 to 2.59), 1.25 (95% CI, 1.09 to 1.42), 0.88 (95% CI, 0.80 to 0.97), and 0.89 (95% CI, 0.68 to 1.16), respectively. Similar inverse associations were observed for dietary isoflavone intake.
CONCLUSION - This study suggests, to the best of our knowledge for the first time, that, among women with lung cancer, prediagnosis intake of soy food is associated with better overall survival.
The authors prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and performed a meta-analysis of published data. Included in the analysis were 71,550 women recruited into the Shanghai Women's Health Study (Shanghai, China) in 1997-2000. Usual soy food intake was assessed at baseline and reassessed during follow-up through in-person interviews. During a mean follow-up period of 9.1 years, 370 incident lung cancer cases were identified; 340 patients were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer (P(trend) = 0.004); the hazard ratio for the highest quintile of intake compared with the lowest was 0.63 (95% confidence interval: 0.44, 0.90). This inverse association appeared predominately among women with later age at menopause (P(interaction) = 0.01) and for aggressive lung cancer as defined by length of survival (<12 months vs. ≥12 months; P(heterogeneity) = 0.057). Meta-analysis of 7 studies conducted among nonsmokers found a summary relative risk of 0.59 (95% confidence interval: 0.49, 0.71) for the highest categories of soy or isoflavone intake versus the lowest. This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive tumors, and its effect may be modified by endogenous estrogens.
BACKGROUND - Whether soy food consumption may protect against coronary heart disease (CHD) remains controversial. No previous study has used biomarkers of soy intake in assessing the relationship between soy consumption and CHD. Biomarkers that reflect both intake and metabolism may be more informative than self-reports of dietary intake.
METHODS - We examined associations of urinary isoflavonoids, a biomarker of soy or soy isoflavone intake, with risk of CHD in a case-control study nested within two prospective cohort studies of Chinese adults in Shanghai. Cases were defined as subjects with no history of CHD at baseline who developed incident CHD during follow-up. Control subjects were randomly selected from those who remained free of CHD and matched to cases by sex, age, date and time of sample collection and antibiotic use. Baseline urinary isoflavonoids (daidzein, genistein, glycitein, equol, O-desmethylangolensin, dihydrodaidzein and dihydrogenistein) were compared between cases (n = 377) and control subjects (n = 753). Conditional logistic regression was used to evaluate the associations.
RESULTS - Total urinary isoflavonoids were not associated with CHD in either women or men. However, urinary equol excretion showed a significant inverse association with CHD in women. The adjusted odds ratios (95% confidence intervals) for CHD across increasing quartiles of equol levels in women were 1 (reference), 0.61 (0.32, 1.15), 0.51 (0.26, 0.98) and 0.46 (0.24, 0.89) (P = 0.02 for trend).
CONCLUSIONS - Our study suggests for the first time that equol, a bioactive metabolite of soy isoflavone daidzein, may be inversely associated with risk of CHD in women.