Soy and tea intake on cervical cancer risk: the Singapore Chinese Health Study.

PURPOSE: Soy isoflavones and tea catechins have immunomodulating and chemopreventive properties relevant for cervical carcinogenesis; however, there are limited epidemiologic data on the relationship of soy and tea consumption with cervical cancer risk. The aim of our study was to examine effects of soy and tea intake on cervical cancer risk among Singapore Chinese women. METHODS: The association between intake of soy and tea drinking and cervical cancer risk was investigated in a prospective, population-based cohort of 30,744 Chinese women in Singapore with an average 16.7 years of follow-up and 312 incident cervical cancer cases. Multivariable proportional hazard models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) of cervical cancer associated with intake levels of soy and tea. RESULTS: High intake of soy alone was associated with a statistically borderline significant 20% reduced risk of cervical cancer (HR 0.80, 95% CI 0.61, 1.05) while green tea alone was not (HR 0.97, 95% CI: 0.76, 1.22). In stratified analysis, high intake of soy was associated with a statistically significant decrease in cervical cancer risk among green tea drinkers (HR 0.43; 95% CI 0.28, 0.69) but not among non-drinkers of green tea. The difference in the soy-cervical cancer risk association between green tea drinkers and non-drinkers was statistically significant (p for interaction = 0.004). This inverse association between soy intake and cervical cancer risk remained after further adjustment for human papillomavirus serostatus. Black tea consumption was not associated with cervical cancer risk. CONCLUSIONS: These findings suggest that a protective effect of soy against cervical cancer development may depend on green tea constituents.

Effect of Green Tea Supplements on Liver Enzyme Elevation: Results from a Randomized Intervention Study in the United States.

Liver injury effects of green tea-based products have been reported in sporadic case reports. However, no study has examined systematically such adverse effects in an unbiased manner. We examined the potential effects of a high, sustained oral dose of green tea extract (GTE) on liver injury measures in a randomized, placebo-controlled, double-blinded phase II clinical trial, which enrolled 1,075 women with the original aim to assess the effect of daily GTE consumption for 12 months on biomarkers of breast cancer risk. The current analysis examined the effect of GTE consumption on liver injury in 1,021 participants (513 in GTE and 508 in placebo arm) with normal baseline levels of liver enzymes. Among women in the GTE arm, alanine aminotransferase (ALT) increased by 5.4 U/L [95% confidence interval (CI), 3.6-7.1] and aspartate aminotransferase increased by 3.8 U/L (95% CI, 2.5-5.1), which were significantly higher than those among women in the placebo arm (both P < 0.001). Overall, 26 (5.1%) women in GTE developed moderate or more severe abnormalities in any liver function measure during the intervention period, yielding an OR of 7.0 (95% CI, 2.4-20.3) for developing liver function abnormalities as compared with those in the placebo arm. ALT returned to normal after dechallenge and increased again after one or more rechallenges with GTE. The rise-fall pattern of liver enzyme values following the challenge-dechallenge cycles of GTE consumption strongly implicates the effect of high-dose GTE on liver enzyme elevations. Cancer Prev Res; 10(10); 571-9. ©2017 AACR.

Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations.

Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies.Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions.Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory.Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and α-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users.Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.

Urinary biomarkers of catechins and risk of hepatocellular carcinoma in the Shanghai Cohort Study.

Dietary catechins are phytochemicals with both antioxidative and prooxidative stress properties. Green tea is a major source of catechins and may be associated with hepatocellular carcinoma (HCC) risk, but the catechin-HCC relationship has not been evaluated using a biomarker-based approach. A nested case-control study of HCC (211 cases and 1,067 matched controls) was conducted within the Shanghai Cohort Study, which enrolled 18,244 men between 1986 and 1989. Concentrations of specific catechins, including epicatechin, epigallocatechin (EGC), and 4'-O-methyl-epigallocatechin, were measured in urine specimens that had been collected prior to HCC diagnosis. None of the catechins measured were associated with HCC risk. In stratified analyses, there was a statistically significant trend for an association of higher urinary EGC with increased HCC risk among subjects with positive serology for hepatitis B surface antigen (P for trend = 0.02). This positive EGC-HCC association became stronger for hepatitis B surface antigen-positive persons who also had low serum retinol levels (for detectable levels vs. undetectable levels, odds ratio = 2.62, 95% confidence interval: 1.25, 5.51). There was no evidence supporting a protective role of catechins in the development of HCC. Instead, exposure to high levels of catechins may increase the risk of developing HCC for high-risk individuals.

Coffee intake and gastric cancer risk: the Singapore Chinese health study.

BACKGROUND: Despite experimental evidence showing chemopreventive effects of coffee-related compounds on gastric carcinogenesis, epidemiologic studies generally do not support coffee-gastric cancer associations. Observational data are lacking among high-risk populations with sufficient regular coffee consumption. METHODS: We examined the association between caffeinated coffee intake and gastric cancer risk in a population-based cohort that enrolled 63,257 Chinese men and women ages 45 to 74 years between 1993 and 1998 in Singapore. Incident gastric cancer cases (n = 647) were identified after a mean follow-up of 14.7 years. Biomarkers of Helicobacter pylori (H. pylori) infection were measured in a subset of gastric cancer cases with blood collected before cancer diagnosis and their matched controls. RESULTS: In the total cohort, daily versus nondaily coffee intake was associated with a statistically nonsignificant decrease in gastric cancer risk [HR = 0.85; 95% confidence interval (CI), 0.69-1.04]. In women, the inverse association strengthened and reached statistical significance (HR = 0.63; 95% CI, 0.46-0.87). In analyses restricted to never smokers and nondrinkers of alcohol, inverse associations strengthened in the total cohort (HR = 0.69; 95% CI, 0.52-0.91) and in women (HR = 0.52; 95% CI, 0.37-0.74). There was no coffee-gastric cancer risk association among men, regardless of smoking status or alcohol consumption. Similar results were observed in the nested case-control study after adjustment for H. pylori infection. CONCLUSION: Daily coffee consumption may reduce the risk of gastric cancer in high-risk populations, especially among women. IMPACT: Research aimed at identifying the compounds in coffee that may protect against gastric carcinogenesis is warranted.

Adherence to a vegetable-fruit-soy dietary pattern or the Alternative Healthy Eating Index is associated with lower hip fracture risk among Singapore Chinese.

Data on overall dietary pattern and osteoporotic fracture risk from population-based cohorts are limited, especially from Asian populations. This study examined the relation between overall diet and hip fracture risk by using principal components analysis (PCA) to identify dietary pattern specific to the study population and by using the Alternative Healthy Eating Index (AHEI) 2010 to assess dietary quality. The Singapore Chinese Health Study is a prospective population-based cohort that enrolled 63,257 Chinese men and women (including both pre- and postmenopausal women) aged 45-74 y between 1993 and 1998 in Singapore. Habitual diet was assessed by using a validated food-frequency questionnaire. Two dietary patterns, the vegetable-fruit-soy (VFS) pattern and the meat-dim-sum (MDS) pattern, were derived by PCA. Overall dietary quality was assessed according to the AHEI 2010, which was defined a priori for chronic disease prevention. A Cox regression model was applied with adjustment for potential confounders. In both genders, higher scores for the VFS pattern and the AHEI 2010 were associated with lower risk of hip fracture in a dose-dependent manner (all P-trend ≤ 0.008). Compared with the lowest quintile, participants in the highest quintile had a 34% reduction in risk (HR: 0.66; 95% CI: 0.55, 0.78) for the VFS pattern and a 32% reduction in risk (HR: 0.68; 95% CI: 0.58, 0.79) for the AHEI 2010. The MDS pattern score was not associated with hip fracture risk. An Asian diet rich in plant-based foods, namely vegetables, fruit, and legumes such as soy, may reduce the risk of hip fracture.

Dietary fiber intake modifies the association between secondhand smoke exposure and coronary heart disease mortality among Chinese non-smokers in Singapore.

OBJECTIVE: Secondhand smoke (SHS) exposure increases the risk for coronary heart disease (CHD) by an estimated 25% to 30% via oxidative stress and inflammatory mechanisms that may be ameliorated by dietary components. The aim of this study was to evaluate the hypothesized modifying role of nutrients with known antioxidant and/or anti-inflammatory properties on the relationship between SHS exposure and CHD mortality. METHODS: Detailed SHS exposure and dietary information was collected among 29,579 non-smokers in the Singapore Chinese Health Study, a prospective population-based cohort. The evaluation of whether or not dietary factors (ß-cryptoxanthin, lutein, ω-3 polyunsaturated fatty acids, fiber, isothiocyanates, and soy isoflavones) modified the relationship between SHS exposure and CHD mortality was conducted within multivariable Cox proportional hazards models by creating an interaction term between the potential dietary effect modifier (lowest quartile of intake versus the second through fourth quartiles of intake) and the SHS exposure (none versus living with at least one smoker[s]). RESULTS: Evidence for a main-effects association between SHS exposure and risk for CHD mortality was not observed. In stratified analyses by levels of selected dietary nutrient intake, fiber modified the effects of SHS exposure on risk for CHD mortality (P for interaction = 0.02). The adjusted hazards ratio for SHS exposure (living with at least one smoker[s] versus living with no smokers) and CHD mortality was 1.62 (95% confidence interval, 1.00-2.63) for those with low-fiber intake. In contrast, among those with high-fiber intake, there was no association with SHS exposure. CONCLUSION: We provide evidence that a diet high in fiber may ameliorate the harmful effects of SHS exposure on risk for CHD mortality.

Calcium intake is not related to breast cancer risk among Singapore Chinese women.

There is experimental evidence that calcium protects against breast cancer development. Prospective epidemiologic studies supporting a protective effect of calcium on breast cancer risk have mainly been limited to Western populations. We examined the association between calcium intake and breast cancer risk in the Singapore Chinese Health Study, a large population-based prospective cohort. Calcium intake and supplement use was assessed by in-person interviewer using a validated food frequency questionnaire. After a mean follow-up of 14.2±3.5 years, 823 cohort participants developed invasive breast cancer. Multivariate proportional hazards regression models were fitted to examine the associations between calcium intake and breast cancer risk. Vegetables were the primary food source of calcium in this study population, followed by dairy products, grains and soy foods. Calcium intake was not associated with breast cancer risk, comparing highest quartile (>345.6 mg/1,000 kcal/day) to lowest quartile (<204.5 mg/1,000 kcal/day) of intake. There was no evidence of effect modification by menopausal status, body mass index, dietary vitamin D or stage of disease at diagnosis. Our findings do not support a hypothesis for calcium in breast cancer chemoprevention, contrary to findings from previous studies among Western populations with higher calcium intake primarily from dairy products and supplements.

Green and black tea intake in relation to prostate cancer risk among Singapore Chinese.

PURPOSE: Tea is one of the most commonly consumed beverages worldwide. To date, observational data from prospective cohort studies investigating the relationship between green and black tea intake and prostate cancer risk are sparse and equivocal. In a population-based, prospective cohort study of Chinese men in Singapore, we investigated the relationship between green and black tea intake and prostate cancer risk. METHODS: Tea consumption data for 27,293 men were collected at baseline (between 1993 and 1998) using a validated food frequency questionnaire. After an average of 11.2 years of follow-up, 298 men had developed prostate cancer. Proportional hazards regression methods were used to assess the associations between tea intake and prostate cancer risk. RESULTS: There was no association between daily green tea intake and prostate cancer risk, compared with no green tea intake [hazard ratio (HR) = 1.08; 95 % confidence interval (CI) 0.79, 1.47]. For black tea, a statistically significant positive association and trend were observed for daily intake compared with no black tea intake (HR = 1.41, 95 % CI 1.03, 1.92; p for trend <0.01) CONCLUSIONS: Few prospective data are available from populations that have both a high level and wide range of black and green tea intake; this study represents a unique opportunity to evaluate their individual effects on prostate cancer risk. Our findings support the notion that green tea intake does not protect against prostate cancer and that black tea intake may increase prostate cancer risk.

Green tea and breast cancer.

The identification of modifiable lifestyle factors that could reduce the risk of breast cancer is a research priority. Despite the enormous chemopreventive potential of green tea and compelling evidence from animal studies, its role in breast cancer development in humans is still unclear. Part of the uncertainty is related to the relatively small number of epidemiological studies on green tea and breast cancer and that the overall results from case-control studies and prospective cohort studies are discordant. In addition, the mechanisms by which green tea intake may influence risk of breast cancer in humans remain not well studied. We review the human studies that have evaluated the relationship between green tea intake and four biomarkers (sex steroid hormones, mammographic density, insulin-like growth factor, adiponectin) that are believed to be important in breast cancer development. Results from these biomarker studies are also inconclusive. Limitations of observational studies and areas of further investigations are discussed.

Green and black tea in relation to gynecologic cancers.

SCOPE: Observational studies have evaluated the relationship between green tea intake and cancers of the ovary and endometrium, but we are not aware of the published studies on green tea intake and risk of human papillomavirus (HPV)-related cancers of the cervix, vagina, or vulva. METHODS AND RESULTS: A critical review of the published literature on tea intake and risk of ovarian and endometrial cancers was conducted. In meta-analyses, we report inverse associations for green tea intake and risk of ovarian cancer (odds ratio [OR]=0.66; 95% confidence interval [CI]: 0.54, 0.80), and for green tea and risk of endometrial cancer (OR=0.78, 95% CI: 0.62, 0.98). There was no association for black tea and ovarian cancer risk (OR=0.94, 95% CI: 0.87, 1.02) and a positive association with endometrial cancer risk (OR=1.20, 95% CI: 1.05, 1.38). We summarized the experimental evidence supporting the antiviral and immunomodulatory activities of green tea catechins, and results from randomized clinical trials that demonstrated green tea catechin efficacy on treatment of cervical lesions and external genital warts. CONCLUSION: Observational data support a protective role of green tea on risk of ovarian and endometrial cancers. Observational data are needed to evaluate whether green tea reduces risk of human papillomavirus-related cancers.

Tea and cancer prevention: epidemiological studies.

Experimental studies have consistently shown the inhibitory activities of tea extracts on tumorigenesis in multiple model systems. Epidemiological studies, however, have produced inconclusive results in humans. A comprehensive review was conducted to assess the current knowledge on tea consumption and risk of cancers in humans. In general, consumption of black tea was not associated with lower risk of cancer. High intake of green tea was consistently associated with reduced risk of upper gastrointestinal tract cancers after sufficient control for confounders. Limited data support a protective effect of green tea on lung and hepatocellular carcinogenesis. Although observational studies do not support a beneficial role of tea intake on prostate cancer risk, phase II clinical trials have demonstrated an inhibitory effect of green tea extract against the progression of prostate pre-malignant lesions. Green tea may exert beneficial effects against mammary carcinogenesis in premenopausal women and recurrence of breast cancer. There is no sufficient evidence that supports a protective role of tea intake on the development of cancers of the colorectum, pancreas, urinary tract, glioma, lymphoma, and leukemia. Future prospective observational studies with biomarkers of exposure and phase III clinical trials are required to provide definitive evidence for the hypothesized beneficial effect of tea consumption on cancer formation in humans.

A vegetable-fruit-soy dietary pattern protects against breast cancer among postmenopausal Singapore Chinese women.

BACKGROUND: Prospective epidemiologic studies in Asian populations consistently show that soy is protective against breast cancer. OBJECTIVE: The objective was to prospectively evaluate whether the protective effect of soy is due to soy isoflavones alone or to their combination with other beneficial dietary factors in an Asian population. DESIGN: Using principal components analysis, we previously identified a "meat-dim sum" pattern characterized by meat, starch, and dim sum items and a "vegetable-fruit-soy" pattern characterized by cruciferous vegetables, fruit, and tofu items in a population-based cohort of Singapore Chinese initiated between 1993 and 1998. Component scores representing intakes of each pattern were used in multivariable Cox regression models to analyze the relation between diet at baseline and breast cancer incidence. RESULTS: As of 31 December 2005, 629 incident breast cancer cases had been diagnosed among the 34,028 women. With greater intake of the vegetable-fruit-soy dietary pattern, we observed a dose-dependent trend (P < 0.01) for decreasing breast cancer risk among postmenopausal women [hazard ratio (HR): 0.70; 95% CI: 0.51, 0.95 for the fourth compared with first quartile]. A stronger association for the vegetable-fruit-soy pattern was observed among postmenopausal women with > or =5 y of follow-up (HR: 0.57; 95% CI: 0.36, 0.88; P for trend <0.01). No trend was observed for a greater intake of the meat-dim sum dietary pattern and increased breast cancer risk. CONCLUSION: Our findings support the hypothesis that a diet characterized by vegetables, fruit, and soy has an early-acting protective effect on breast carcinogenesis.

Polyunsaturated fatty acids, DNA repair single nucleotide polymorphisms and colorectal cancer in the Singapore Chinese Health Study.

Animal and in vitrostudies support a role for polyunsaturated fatty acids (PUFAs) in colon carcinogenesis; however, the epidemiological evidence is inconclusive. Recently, we investigated their role within the Singapore Chinese Health Study, a population-based cohort of Singapore Chinese men and women. We reported that a high intake of marine n-3 PUFAs was associated with an increased risk of colorectal cancer (CRC). Oxidation of PUFAs incorporated into cell membranes generates lipid hydroperoxides, which can be mutagenic. In this report, we investigated whether single nucleotide polymorphisms (SNPs) in DNA repair genes modified the effect of PUFAs on CRC risk using a nested case-control study within the Singapore Chinese Health Study. We genotyped 1,181 controls and 311 cases (180 colon and 131 rectal cancer) for SNPs in the XRCC1 (Arg194Trp, Arg399Gln), OGG1 (Ser326Cys), PARP (Val762Ala, Lys940Arg), and XPD (Asp312Asn, Lys751Gln) genes. We observed that the PARP Val762Ala SNP modified the association between marine n-3 PUFA and rectal cancer risk, with no evidence of interaction among colon cancer (heterogeneity test p=0.003). Our results suggest a positive association between high intake of marine n-3 PUFA and rectal cancer risk among carriers of at least one PARP codon 762 Ala allele (odds ratio=1.7, 95% confidence interval=1.1-2.7).

Marine n-3 and saturated fatty acids in relation to risk of colorectal cancer in Singapore Chinese: a prospective study.

Experimental data support multiple roles for fatty acids in colorectal carcinogenesis. We examined dietary fatty acids and incidence of colorectal cancer, and evaluated effect modification by sex and stage of disease among a population-based cohort of 61,321 Singapore Chinese that was established between 1993 and 1998. As of December 31, 2005, 961 incident colorectal cancers were diagnosed. Presented hazard ratios (HRs) are for highest versus lowest quartiles with adjustment for potential confounders. Among women, we observed a dose-dependent, positive association between saturated fat and localized colorectal cancer (Dukes A or B) [(HR=1.69, 95% confidence interval (CI)=1.08-2.63, p for trend=0.01)]. No such associations were noted in men (p for interaction by sex=0.04). Marine n-3 polyunsaturated fatty acid (PUFA) intake was positively associated with advanced disease (Dukes C or D) (HR=1.33, 95% CI=1.05-1.70, p for trend=0.01), regardless of sex. The association with marine n-3 PUFAs was strongest among those with the shortest (10 years) (HR=0.62, 95% CI=0.29-1.34, p for trend=0.55). Our findings suggest that subtypes of fatty acids may differentially influence risk of colorectal cancer of a specified stage.