Low-Carbohydrate Diet Score and the Risk of Colorectal Cancer: Findings from the Singapore Chinese Health Study.

BACKGROUND: Colorectal cancer is common cancer with a high mortality rate. Low-carbohydrate diet (LCD) score holistically evaluates the LCD pattern from carbohydrate, protein, and fat intake. Epidemiologic data of LCD-colorectal cancer association are sparse. METHODS: We evaluated the associations between LCD (i.e., total, animal- and plant-based) and colorectal cancer risk in the Singapore Chinese Health Study, a population-based prospective cohort study including 61,321 Chinese in Singapore who were 45 to 74 years old at baseline. Cox proportional hazard regression model was used to determine the HRs and respective 95% confidence intervals (CI) for colorectal cancer associated with LCD after adjusting for potential confounders, including age, sex, BMI, physical activity, family history of colorectal cancer, etc. RESULTS: After an average of 19.5 years of follow-up, 2,520 participants developed colorectal cancer (1,608 colon cancer and 912 rectal cancer). Overall, the association between total or plant-based LCD scores with the risk of colorectal, colon, or rectal cancer was null (all Ptrend ≥ 0.28). The animal-based LCD was modestly associated with colon cancer risk (Ptrend = 0.02), but not with rectal cancer. Compared with the lowest quartile, HRs (95% CIs) of colon cancer for quartiles 2, 3, and 4 of animal-based LCD were 1.12 (0.98-1.29), 1.27 (1.10-1.46), and 1.14 (0.99-1.31), respectively. CONCLUSIONS: A low-level carbohydrate diet with a high level of animal protein and fat was associated with a moderate increase in the risk of colon cancer among Chinese Singaporeans. IMPACT: High consumption of animal protein/fat and low consumption of carbohydrates may increase colon cancer risk.

Coffee and tea consumption and mortality from all causes, cardiovascular disease and cancer: a pooled analysis of prospective studies from the Asia Cohort Consortium.

BACKGROUND: Accumulating evidence suggests that consuming coffee may lower the risk of death, but evidence regarding tea consumption in Asians is limited. We examined the association between coffee and tea consumption and mortality in Asian populations. METHODS: We used data from 12 prospective cohort studies including 248 050 men and 280 454 women from the Asia Cohort Consortium conducted in China, Japan, Korea and Singapore. We estimated the study-specific association of coffee, green tea and black tea consumption with mortality using Cox proportional-hazards regression models and the pooled study-specific hazard ratios (HRs) using a random-effects model. RESULTS: In total, 94 744 deaths were identified during the follow-up, which ranged from an average of 6.5 to 22.7 years. Compared with coffee non-drinkers, men and women who drank at least five cups of coffee per day had a 24% [95% confidence interval (CI) 17%, 29%] and a 28% (95% CI 19%, 37%) lower risk of all-cause mortality, respectively. Similarly, we found inverse associations for coffee consumption with cardiovascular disease (CVD)-specific and cancer-specific mortality among both men and women. Green tea consumption was associated with lower risk of mortality from all causes, CVD and other causes but not from cancer. The association of drinking green tea with CVD-specific mortality was particularly strong, with HRs (95% CIs) of 0.79 (0.68, 0.91) for men and 0.78 (0.68, 0.90) for women who drank at least five cups per day of green tea compared with non-drinkers. The association between black tea consumption and mortality was weak, with no clear trends noted across the categories of consumption. CONCLUSIONS: In Asian populations, coffee consumption is associated with a lower risk of death overall and with lower risks of death from CVD and cancer. Green tea consumption is associated with lower risks of death from all causes and CVD.

The association between dietary vitamin B12 and lung cancer risk: findings from a prospective cohort study.

BACKGROUND: Since previous epidemiological studies reported inconsistent associations between dietary vitamin B12 intake and lung cancer risk, more studies are warranted to clarify this association in different populations. METHODS: The association between dietary B12 intake and lung cancer risk was examined in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63 257 Singaporean Chinese men and women, 45-74 years of age at enrollment during 1993-1998 and were followed up for incidence of lung cancer for up to 25 years. Dietary vitamin B12 intake was derived from a validated food frequency questionnaire. Cox proportional hazard regression method was used to estimate hazard ratio and 95% confidence interval (CI) of lung cancer associated with dietary vitamin B12 intake with adjustment for multiple potential confounders. RESULTS: After a mean follow-up of 17.64 years, 2001 study participants developed lung cancer. High levels of vitamin B12 intake were associated with significantly increased risk of lung cancer (Ptrend = 0.03). Compared with the lowest quintile, hazard ratios (95% CIs) of lung cancer for quintile 2, 3, 4, and 5 of vitamin B12 intake were 1.09 (0.95-1.25), 1.11 (0.96-1.28), 1.11 (0.97-1.29) and 1.18 (1.03-1.35), respectively. This positive association was more apparent in men than in women, in adenocarcinoma patients, or in participants with equal or less than 2 years follow-up than those with longer duration of follow-up. CONCLUSION: Higher intake of dietary vitamin B12 was associated with increased risk of lung cancer. This highlights the potential harmful effect of vitamin B12 supplementation for lung cancer.

Dietary Antioxidants and Risk of Parkinson's Disease in the Singapore Chinese Health Study.

BACKGROUND: Despite experimental evidence implicating oxidative stress in the pathogenesis of PD, epidemiological studies have provided inconsistent associations between dietary antioxidants and risk of developing PD. Furthermore, no study has been done in any Asian population. OBJECTIVES: We examined the associations for intake levels of dietary carotenoids (α-carotene, ß-carotene, lycopene, ß-cryptoxanthin, and lutein) and vitamins (vitamin A, C and E) and the risk of developing PD. METHODS: We used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63,257 men and women aged 45 to 74 years during enrollment in 1993-1998. Antioxidant intake was derived from a validated semiquantitative food frequency questionnaire. Incident cases were identified through follow-up interviews, hospital records, or PD registries through 31 July 2018. Hazard ratios and corresponding 95% confidence intervals were derived from multivariable Cox proportional hazard regression models with adjustment for other lifestyle and dietary factors. RESULTS: During an average 19.4 years of follow-up, 544 incident PD cases were identified. No association was found for dietary carotenoids, individually or summed. Hazard ratio comparing highest to lowest quartile for total carotenoids was 0.98 (95% confidence interval: 0.76-1.28; Ptrend = 0.83). There were also no clear dose-dependent associations of dietary vitamins A, C, and E with risk of developing PD (all Ptrend ≥ 0.10). Sensitive analyses with lag time and excluding supplement use did not materially alter results. CONCLUSIONS: Intake of dietary antioxidants, such as carotenoids and vitamins, was not associated with the risk of developing PD in Singaporean Chinese. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Associations between tea and coffee beverage consumption and the risk of lung cancer in the Singaporean Chinese population.

BACKGROUND: Tea and coffee are widely consumed beverages. Tea flavonoids have been shown to inhibit lung tumorigenesis using in vitro and in vivo models. Conversely, coffee contains complex mixtures of biochemically active compounds, some of which may have genotoxic and mutagenic properties. However, previous epidemiologic studies have shown inconsistent results on tea and coffee in relation to lung cancer risk. METHODS: The Singapore Chinese Health Study is a population-based prospective cohort of 63,257 Singaporean Chinese men and women, with an average of 17.7 years of follow-up. Information on tea and coffee consumption and other lifestyle factors was collected through in-person interviews at baseline. Multivariable Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations with adjustment for potential confounders. RESULTS: There were 1486 incident lung cancer cases. Compared to non-daily coffee drinkers, HRs (95% CIs) of lung cancer risk for those consuming one, two, and three or more cups of coffee per day were 1.18 (1.02-1.36), 1.21 (1.05-1.40), and 1.32 (1.08-1.62) respectively (P for trend = 0.0034). The highest category of black tea consumption (at least 2 cups per day) was inversely associated with risk of lung cancer [HR (95% CI) = 0.73 (0.53-0.99)], particularly among men [HR (95% CI) = 0.67 (0.47-0.95)], compared to less-than-weekly black tea drinkers, although the interaction by sex was not statistically significant. CONCLUSIONS: Coffee beverage consumption was associated with higher risk of developing lung cancer. On the other hand, black tea intake was associated with lower risk of lung cancer among men in our cohort, and further studies are needed to confirm this association.

Fish and marine fatty acids intakes, the FADS genotypes and long-term weight gain: a prospective cohort study.

OBJECTIVE: We tested whether genetic variants near fatty acid desaturases gene (FADS) cluster, which were recently identified to be signatures of adaptation to fish-rich and n-3 polyunsaturated fatty acids (PUFAs)-rich diet, interacted with these dietary factors on change in body mass index (BMI). DESIGN: Three FADS variants were examined for gene-diet interactions on long-term (~10 years) changes in BMI and body weight in four prospective cohort studies. SETTING: Population based study. PARTICIPANTS: 11 323 women from the Nurses' Health Study (NHS), 6833 men from the Health Professionals Follow-up Study (HPFS) and replicated in 6254 women from the Women's Health Initiative (WHI) and 5 264 Chinese from the Singapore Chinese Health Study (SCHS). MAIN OUTCOMES: Long-term (~10 years) changes in BMI and body weight. RESULTS: In the NHS and HPFS cohorts, food-sourced n-3 PUFAs intake showed interactions with the FADS rs174570 on changes of BMI (P for interaction=0.02 in NHS, 0.05 in HPFS and 0.007 in combined). Such interactions were replicated in two independent cohorts WHI and SCHS (P for interaction=0.04 in WHI, 0.02 in SCHS and 0.001 in combined). The genetic associations of the FADS rs174570 with changes in BMI increased across the tertiles of n-3 PUFAs in all the cohorts. Fish intake also accentuated the genetic associations of the FADS rs174570 with long-term changes in BMI (pooled P for interaction=0.006). Viewed differently, long chain n-3 PUFAs intake showed stronger association with long-term changes in BMI among the rs174570 T carriers (beta=0.79 kg/m2 per g, p=3×10-5) than the rs174570 non-T carriers (beta=0.16 kg/m2 per g, p=0.08). Similar results were observed for fish intake. CONCLUSIONS: Our hypothesis-driven analyses provide replicable evidence that long chain n-3 PUFAs and fish intakes may interact with the FADS variant on long-term weight gain. Further investigation is needed to confirm our findings in other cohorts.

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.

Green Tea Catechin Extract Supplementation Does Not Influence Circulating Sex Hormones and Insulin-Like Growth Factor Axis Proteins in a Randomized Controlled Trial of Postmenopausal Women at High Risk of Breast Cancer.

BACKGROUND: Consumption of green tea has been associated with reduced risk of breast cancer. Hormonal modulation has been suggested as one of the potential underlying mechanisms; however, it has yet to be fully elucidated in large, long-term human clinical trials. OBJECTIVE: We investigated the effects of decaffeinated green tea extract (GTE) on circulating sex hormones and insulin-like growth factor (IGF) proteins. METHODS: We conducted a placebo-controlled double-blind randomized clinical trial recruiting from 8 clinical centers in Minnesota. Participants were 538 healthy postmenopausal women randomly assigned to the GTE group (463 completed the study; mean age = 60.0 y) and 537 to the placebo group (474 completed; mean age = 59.7 y). Women in the GTE group orally took 4 decaffeinated capsules containing 1315 mg total catechins including 843 mg epigallocatechin-3-gallate daily for 1 y, whereas women in the placebo group took similar capsules containing no tea catechins. Blood sex hormones (estrone, estradiol, androstenedione, testosterone, and sex hormone-binding globulin) and IGF proteins (IGF-1 and IGF binding protein-3) were quantified at baseline and months 6 (for IGF proteins only) and 12, and were assessed as secondary outcomes of the study using a mixed-effect repeated-measures ANOVA model. RESULTS: Women in the GTE group had significantly higher blood total estradiol (16%; P = 0.02) and bioavailable estradiol (21%; P = 0.03) than in the placebo group at month 12. There was a statistically significant interaction between GTE supplementation and duration of treatment on estradiol and bioavailable estradiol (both Ps for interaction = 0.001). The catechol-O-methyltransferase genotype did not influence blood sex hormones before or after GTE supplementation. The circulating concentrations of IGF proteins were comparable between GTE and placebo groups at all 3 time points. CONCLUSION: These results suggest that a 12-mo GTE supplementation significantly increases circulating estradiol concentrations in healthy postmenopausal women. This trial was registered at clinicaltrials.gov as NCT00917735.

Coffee, tea, caffeine, and risk of nonmelanoma skin cancer in a Chinese population: The Singapore Chinese Health Study.

BACKGROUND: Although epidemiologic studies in populations of European descent suggest a possible chemoprotective effect of caffeine against nonmelanoma skin cancer (NMSC), data in Asian populations are lacking. OBJECTIVES: We examined the relationship of coffee, tea, and caffeine consumption with NMSC risk among Chinese in Singapore. METHODS: We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women who were 45 to 74 years old at recruitment from 1993 to 1998. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by using multivariable Cox proportional hazard models. RESULTS: Coffee drinking was associated with reduced NMSC risk in a dose-dependent manner (P trend < .0001). Compared with those who drank coffee less than weekly, those who drank 3 or more cups per day had a lower risk of basal cell carcinoma (HR, 0.54; 95% CI, 0.31-0.93) and a lower risk of squamous cell carcinoma (HR, 0.33; 95% CI, 0.13-0.84). Compared with nondrinkers of black tea, daily drinkers of black tea also had a reduced risk of NMSC (HR, 0.70; 95% CI, 0.52-0.94). Caffeine intake reduced NMSC risk in a stepwise manner (P trend = .0025); subjects with a caffeine intake of 400 mg/d or more had the lowest risk (HR, 0.59; 95% CI, 0.34-1.04). CONCLUSION: Consumption of caffeinated drinks such as coffee and black tea may reduce the risk of NMSC among Chinese.

Is high vitamin B12 status a cause of lung cancer?

Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer etiology via direct measurements of pre-diagnostic circulating vitamin B12 concentrations in a nested case-control study, complemented with a Mendelian randomization (MR) approach in an independent case-control sample. We used pre-diagnostic biomarker data from 5183 case-control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls. Exposures included directly measured circulating vitamin B12 in pre-diagnostic blood samples from the nested case-control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study. Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations. We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12 ] = 1.15, 95% confidence interval (95%CI) = 1.06-1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD ] = 1.08, 95%CI = 1.00-1.16). Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.

Consumption of Coffee but Not of Other Caffeine-Containing Beverages Reduces the Risk of End-Stage Renal Disease in the Singapore Chinese Health Study.

Background: Cross-sectional studies suggest that coffee drinking is associated with better renal function. However, to our knowledge, no prospective study has examined its relation with the risk of end-stage renal disease (ESRD). Objective: We examined the relations between coffee, tea, soda, and total caffeine consumption and the risk of ESRD among middle-aged and older Chinese in Singapore. Methods: We used data from the Singapore Chinese Health Study, a prospective cohort of 63,257 men and women aged 45-74 y at recruitment from 1993 to 1998. Baseline information on the consumption of caffeinated coffee and other caffeinated beverages (tea and sodas), habitual diet, medical history, and lifestyle factors was obtained via in-person interviews. The standard serving size of 1 cup was assigned as 237 mL in the questionnaire. Incident ESRD cases were identified via linkage with the nationwide registry. We used multivariable Cox regression models to estimate HRs and 95% CIs of ESRD risk associated with the consumption of caffeinated beverages, with adjustment for potential confounders. Results: After a mean follow-up of 16.8 y, 1143 cohort subjects developed ESRD. Compared with those who drank coffee less than daily, the HR (95% CI) was 0.91 (0.79, 1.05) for those who drank 1 cup of coffee/d and 0.82 (0.71, 0.96) for those who drank ≥2 cups/d (P-trend = 0.012). When stratified by sex, this association was observed in men but not in women. Compared with those who drank less than daily, the HR (95% CI) for drinking ≥2 cups/d was 0.71 (0.57, 0.87) among men and 0.97 (0.78, 1.19) among women (P-interaction = 0.03). Conversely, intakes of tea, soda, or total caffeine were not associated with the risk of ESRD in multivariable models. Conclusion: The consumption of ≥2 cups of coffee/d may reduce the risk of ESRD in the general population, especially among men. This study was registered at http://www.clinicaltrials.gov as NCT03356340.

Effects of stocking density on growth performance, meat quality and tibia development of Pekin ducks.

This study was performed to investigate the effects of stocking density on performance, meat quality and tibia development in Pekin ducks reared on a plastic wire floor. A total of 372 healthy, 21-day-old, male ducks with similar body weight (BW) were randomly allotted to stocking densities of five (low), eight (medium) and 11 (high) birds/m2 . Each group had six replicates. Results showed that compared with the low density group, medium and high stocking density caused a decrease in final BW at 42 days old, and in average daily gain, European performance index (p < .01) and meat pH at 45 min postmortem (p < .001), and an increase of meat drip loss (p < .01). High stocking density resulted in an increase of feed/gain ratio (p < .001), but a decrease of tibia calcium (p < .01) and phosphorus content (p < .05). Meat color, shear force values, tibia size (weight, length, and width) and breaking strength were not significantly influenced by stocking density. In conclusion, stocking density over eight birds/m2 negatively affects growth performance, but meat quality and tibia development are not dramatically influenced. Based on this study, the stocking density of male Pekin ducks should be adjusted between five and eight birds/m2 .

Coffee and tea drinking in relation to risk of hip fracture in the Singapore Chinese Health Study.

Meta-analyses of studies conducted among Western populations suggest that coffee consumption does not affect osteoporotic fracture risk. However, experimental studies have shown that the effect of caffeine on bone health may depend on dosage. We examined the associations between consumption of coffee, tea and caffeine and risk of hip fracture in an Asian cohort. In a population-based prospective cohort of 63,257 Chinese men and women aged 45-74 years in Singapore, a validated semi-quantitative food frequency questionnaire was used to assess habitual consumption of coffee and tea at baseline. Cox proportional hazards regression models were used to estimate hazard ratio (HR) and 95% confidence interval (CI) for risk of hip fracture with adjustment for potential confounders. During a mean follow-up of 16.7 years, 2502 incident hip fracture cases were identified. Compared to coffee drinkers <1 cup/week, those who drank ≥4 cups/day had a statistically significant higher risk to develop hip fractures, the HR (95% CI) was 1.32 (1.07, 1.63) in the whole cohort analysis, 1.46 (1.01, 2.10) for men and 1.33 (1.02, 1.72) for women. Among postmenopausal women, compared to those who drank coffee <1 cup/week, drinking 2-3 cups/day was associated with the lowest risk [HR: 0.88 (0.76, 1.01)] and drinking ≥4 cups/day was associated with the highest risk [HR: 1.31 (1.00, 1.71)]. Similar associations with caffeine intake were found among postmenopausal women. Restricted spline analyses suggested a non-linear association between coffee/caffeine consumption and hip fracture risk in postmenopausal women (p for non-linearity ≤ 0.05). No association was found with tea consumption in either sex. These data suggest that drinking coffee ≥4 cups/day is associated with a higher hip fracture risk, while a moderate intake may alleviate risk in postmenopausal women. Future studies should corroborate these results to determine levels of optimal coffee consumption in relation to bone health.

Coffee, tea, caffeine, and risk of hypertension: The Singapore Chinese Health Study.

PURPOSE: The relationship between coffee and tea, and risk of hypertension remains controversial in Western populations. We investigated these associations in an Asian population. METHODS: The Singapore Chinese Health Study is a population-based prospective cohort that recruited 63,257 Chinese aged 45-74 years and residing in Singapore from 1993 to 1998. Information on consumption of coffee, tea, and other lifestyle factors was collected at baseline, and self-reported physician-diagnosed hypertension was assessed during two follow-up interviews (1999-2004, 2006-2010). RESULTS: We identified 13,658 cases of incident hypertension after average 9.5 years. Compared to those who drank one cup of coffee/day, the hazard ratios (HR) and 95% confidence intervals (CI) were 0.87 (0.83-0.91) for

A Randomized Controlled Trial of Green Tea Extract Supplementation and Mammographic Density in Postmenopausal Women at Increased Risk of Breast Cancer.

Epidemiologic and animal studies suggest a protective role of green tea against breast cancer. However, the underlying mechanism is not understood. We conducted a randomized, double-blinded, placebo-controlled phase II clinical trial to investigate whether supplementation with green tea extract (GTE) modifies mammographic density (MD), as a potential mechanism, involving 1,075 healthy postmenopausal women. Women assigned to the treatment arm consumed daily 4 decaffeinated GTE capsules containing 1,315 mg total catechins, including 843 mg epigallocatechin-3-gallate (EGCG) for 12 months. A computer-assisted method (Madena) was used to assess MD in digital mammograms at baseline and month 12 time points in 932 completers (462 in GTE and 470 in placebo). GTE supplementation for 12 months did not significantly change percent MD (PMD) or absolute MD in all women. In younger women (50-55 years), GTE supplementation significantly reduced PMD by 4.40% as compared with the placebo with a 1.02% PMD increase from pre- to postintervention (P = 0.05), but had no effect in older women (Pinteraction = 0.07). GTE supplementation did not induce MD change in other subgroups of women stratified by catechol-O-methyltransferase genotype or level of body mass index. In conclusion, 1-year supplementation with a high dose of EGCG did not have a significant effect on MD measures in all women, but reduced PMD in younger women, an age-dependent effect similar to those of tamoxifen. Further investigation of the potential chemopreventive effect of green tea intake on breast cancer risk in younger women is warranted. Cancer Prev Res; 10(12); 710-8. ©2017 AACR.

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.

Ambient ultraviolet radiation exposure and hepatocellular carcinoma incidence in the United States.

BACKGROUND: Hepatocellular carcinoma (HCC), the most commonly occurring type of primary liver cancer, has been increasing in incidence worldwide. Vitamin D, acquired from sunlight exposure, diet, and dietary supplements, has been hypothesized to impact hepatocarcinogenesis. However, previous epidemiologic studies examining the associations between dietary and serum vitamin D reported mixed results. The purpose of this study was to examine the association between ambient ultraviolet (UV) radiation exposure and HCC risk in the U.S. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database provided information on HCC cases diagnosed between 2000 and 2014 from 16 population-based cancer registries across the U.S. Ambient UV exposure was estimated by linking the SEER county with a spatiotemporal UV exposure model using a geographic information system. Poisson regression with robust variance estimation was used to calculate incidence rate ratios (IRRs) and 95% confidence intervals (CIs) for the association between ambient UV exposure per interquartile range (IQR) increase (32.4 mW/m2) and HCC risk adjusting for age at diagnosis, sex, race, year of diagnosis, SEER registry, and county-level information on prevalence of health conditions, lifestyle, socioeconomic, and environmental factors. RESULTS: Higher levels of ambient UV exposure were associated with statistically significant lower HCC risk (n = 56,245 cases; adjusted IRR per IQR increase: 0.83, 95% CI 0.77, 0.90; p < 0.01). A statistically significant inverse association between ambient UV and HCC risk was observed among males (p for interaction = 0.01) and whites (p for interaction = 0.01). CONCLUSIONS: Higher ambient UV exposure was associated with a decreased risk of HCC in the U.S. UV exposure may be a potential modifiable risk factor for HCC that should be explored in future research.

Tea Drinking and Its Association with Active Tuberculosis Incidence among Middle-Aged and Elderly Adults: The Singapore Chinese Health Study.

Experimental studies showed that tea polyphenols may inhibit growth of Mycobacterium tuberculosis. However, no prospective epidemiologic study has investigated tea drinking and the risk of active tuberculosis. We investigated this association in the Singapore Chinese Health Study, a prospective population-based cohort of 63,257 Chinese aged 45-74 years recruited between 1993 and 1998 in Singapore. Information on habitual drinking of tea (including black and green tea) and coffee was collected via structured questionnaires. Incident cases of active tuberculosis were identified via linkage with the nationwide tuberculosis registry up to 31 December 2014. Cox proportional hazard models were used to estimate the relation of tea and coffee consumption with tuberculosis risk. Over a mean 16.8 years of follow-up, we identified 1249 incident cases of active tuberculosis. Drinking either black or green tea was associated with a dose-dependent reduction in tuberculosis risk. Compared to non-drinkers, the hazard ratio (HR) (95% confidence interval (CI)) was 1.01 (0.85-1.21) in monthly tea drinkers, 0.84 (0.73-0.98) in weekly drinkers, and 0.82 (0.71-0.96) in daily drinkers (p for trend = 0.003). Coffee or caffeine intake was not significantly associated with tuberculosis risk. In conclusion, regular tea drinking was associated with a reduced risk of active tuberculosis.

Dietary Intake of Antioxidant Vitamins and Carotenoids and Risk of Developing Active Tuberculosis in a Prospective Population-Based Cohort Study.

Antioxidants may protect against oxidative stress, which is associated with tuberculosis (TB) disease. However, direct evidence for a protective association between dietary antioxidants and TB incidence in humans has been lacking. The relationship between intake of antioxidant vitamins (vitamins A, C, D, and E) and individual carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lycopene, and lutein) and TB incidence was examined in the Singapore Chinese Health Study, a prospective cohort study of 63,257 adults aged 45-74 years enrolled during 1993-1998. Baseline intake of these antioxidants was estimated using a validated semiquantitative food frequency questionnaire including questions on use of dietary supplements. After an average of 16.9 years of follow-up, 1,186 incident active TB cases were identified among cohort participants. Compared with the lowest quartile, reduced risk of active TB was observed for the highest quartile of vitamin A intake (hazard ratio = 0.71, 95% confidence interval: 0.59, 0.85; P-trend < 0.01) and ß-carotene intake (hazard ratio = 0.76, 95% confidence interval: 0.63, 0.91; P-trend < 0.01), regardless of smoking status. Lower TB risk was seen for vitamin C intake among current smokers only. Other vitamins and carotenoids were not associated with TB risk. These results suggest that vitamin C may reduce TB risk among current smokers by ameliorating oxidative stress, while vitamin A and ß-carotene may have additional antimycobacterial properties.

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.