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Simple Summary: Serine and glycine have an important role in the folate-dependent one-carbon metabolism. No prior epidemiologic study has evaluated the associations for serum levels of serine and glycine with pancreatic cancer risk. We performed a nested case-control study of 129 incident pancreatic cancer cases and 258 individually matched controls within the Shanghai Cohort Study, a prospective cohort study involving 18,244 male residents in Shanghai, China. We found that the risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of serine and glycine in serum collected, on average, more than 10 years prior to cancer diagnosis. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for pancreatic cancer prevention. Background. Serine and glycine play an important role in the folate-dependent one-carbon metabolism. The metabolism of serine and glycine has been shown to be associated with cancer cell proliferation. No prior epidemiologic study has investigated the associations for serum levels of serine and glycine with pancreatic cancer risk. Methods. We conducted a nested case-control study involved 129 incident pancreatic cancer cases and 258 individually matched controls within a prospective cohort study of 18,244 male residents in Shanghai, China. Glycine and serine and related metabolites in pre-diagnostic serum were quantified using gas chromatography-tandem mass spectrometry. A conditional logistic regression method was used to evaluate the associations for serine, glycine, and related metabolites with pancreatic cancer risk with adjustment for potential confounders. Results: Odds ratios (95% confidence intervals) of pancreatic cancer for the highest quartile of serine and glycine were 0.33 (0.14–0.75) and 0.25 (0.11–0.58), respectively, compared with their respective lowest quartiles (both p's < 0.01). No significant association with risk of pancreatic cancer was observed for other serine- or glycine related metabolites including cystathionine, cysteine, and sarcosine. Conclusion. The risk of pancreatic cancer was reduced by more than 70% in individuals with elevated levels of glycine and serine in serum collected, on average, more than 10 years prior to cancer diagnosis in a prospectively designed case-control study. These novel findings support a protective role of serine and glycine against the development of pancreatic cancer in humans that might have an implication for cancer prevention. [ABSTRACT FROM AUTHOR]

Background: The role of smoking in nasopharyngeal carcinoma (NPC) remains uncertain, especially in endemic regions. We conducted an individual participant data (IPD) meta-analysis of prospective cohort studies to investigate the associations between smoking exposure and risk of NPC.Methods: We obtained individual participant data of 334 935 male participants from six eligible population-based cohorts in NPC-endemic regions, including two each in Guangzhou and Taiwan, and one each in Hong Kong and Singapore. We used one- and two-stage approaches IPD meta-analysis and Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of NPC for smoking exposure adjusting for age and drinking status.Results: During 2 961 315 person-years of follow-up, 399 NPC evens were ascertained. Risks of NPC were higher in ever versus never smokers (HRone-stage = 1.32, 95% CI = 1.07-1.63, P = 0.0088; HRtwo-stage = 1.27, 1.01-1.60, 0.04). These positive associations appeared to be stronger in ever smokers who consumed 16+ cigarettes/day (HRone-stage = 1.67, 95% CI = 1.29-2.16, P = 0.0001), and in those who started smoking at age younger than 16 (2.16, 1.33-3.50, 0.0103), with dose-response relationships (P-values for trend = 0.0028 and 0.0103, respectively). Quitting (versus daily smoking) showed a small reduced risk (stopped for 5+ years: HRone-stage = 0.91, 95% CI = 0.60-1.39, P = 0.66; for former smokers: HRtwo-stage = 0.84, 0.61-1.14, 0.26).Conclusions: This first IPD meta-analysis from six prospective cohorts in endemic regions has provided robust observational evidence that smoking increased NPC risk in men. NPC should be added to the 12-16 cancer sites known to be tobacco-related cancers. Strong tobacco control policies, preventing young individuals from smoking, would reduce NPC risk in endemic regions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Diet and inflammation have been suggested to be important risk factors for lung cancer. We examined the ability of the dietary inflammatory index (DII®) to predict lung cancer in the Singapore Chinese Health Study (SCHS). The DII is a diet quality index based on the literature linking foods and nutrients with inflammatory biomarkers. Patients and methods: Using data from the SCHS for 60,232 participants, including 1851 lung cancer cases, we investigated the associations of baseline DII scores calculated from a food frequency questionnaire with risk of developing lung cancer over an average of 17.6 years of follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors. Results: After excluding cancers diagnosed in the first 2 years of follow-up, the DII was non-significantly associated with risk of lung cancer (HRQ5vsQ1 = 1.13; 95% CI 0.94–1.35; P-trend = 0.24) after adjusting for age, dialect group, sex, interview year, education, body mass index, total calorie intake, physical activity and various smoking variables. In stratified analysis, stronger, statistically significant associations were evident in current smokers (HR 1.44; 95% CI 1.11–1.86; Ptrend = 0.03, P for interaction = 0.003) and in male ever-smokers (HRQ5vsQ1 = 1.37; 95% CI 1.07–1.77; P-trend = 0.03). Conclusion: A pro-inflammatory diet, as shown by higher DII scores, is associated with an elevated risk of lung cancer for subjects with a history of smoking. Public health measures should be adopted to promote consumption of a healthy, anti-inflammatory diet to reduce the risk of lung cancer, especially in current and former smokers. [ABSTRACT FROM AUTHOR]

Introduction: Telomeres and telomerase play important role in maintaining chromosome integrity and genomic stability. Recent epidemiologic data showed inconsistent findings which suggested that both short and long leukocyte telomeres could be associated with increased risk of pancreatic cancer. We prospectively examined the association between telomere length and pancreatic cancer risk in a population-based cohort study. Methods: The Singapore Chinese Health Study recruited 63,257 Chinese aged 45 to 74 years from 1993 to 1998 in Singapore. Relative telomere length in peripheral blood leukocytes was quantified using a validated monochrome multiplex quantitative polymerase chain reaction method in 26,540 participants, including 116 participants who later developed pancreatic cancer after an average of 13 years of follow-up. Cox proportional hazard regression method was used to calculate hazard ratio (HR) and its 95% confidence interval (CI) of pancreatic cancer risk associated with telomere length, with adjustment for confounding factors. Results: Longer telomeres were significantly associated with higher risk of pancreatic cancer (Ptrend = 0.02). Compared with lowest quartile, subjects with highest quartile of telomere length had an HR of 2.18 (95% CI: 1.25–3.80) for developing pancreatic cancer. In stratified analysis, this association remained among pancreatic adenocarcinoma patients but not among pancreatic non-adenocarcinoma patients. In continuous scale, the HRs and 95% CIs were 3.08 (1.17–8.11) for adenocarcinoma patients and 1.47 (0.43–5.06) for non-adenocarcinoma patients. The HRs and 95% CIs of the highest quartile of telomere length, compared with the lowest quartile, for adenocarcinoma and non-adenocarcinoma were 2.50 (1.22–5.13) and 1.63 (0.66–4.03), respectively. The length of follow-up from the collection of blood for the measurement of telomere length to the diagnosis of cancer (median = 8.0, range: from 5.0 months to 16.2 years) had no significant impact on the association between telomere length and pancreatic cancer risk. Conclusions: The present study demonstrates that longer telomeres are associated with increased risk of overall pancreatic cancer. [ABSTRACT FROM AUTHOR]

Purpose: Mechanistic and observational data together support a role for prolactin in breast cancer development. Determinants of prolactin in Asian populations have not been meaningfully explored, despite the lower risk of breast cancer in Asian populations.Methods: Determinants of plasma prolactin were evaluated in 442 postmenopausal women enrolled in the Singapore Chinese Health Study, a population-based prospective cohort study. At baseline all cohort members completed an in-person interview that elicited information on diet, menstrual and reproductive history, and lifestyle factors. One year after cohort initiation we began collecting blood samples. Quantified were plasma concentrations of prolactin, estrone, estradiol, testosterone, androstenedione, and sex hormone-binding globulin (SHBG). Analysis of covariance method was used for statistical analyses with age at blood draw, time since last meal, and time at blood draw as covariates.Results: Mean prolactin levels were 25.1% lower with older age at menarche (p value = 0.001), and 27.6% higher with greater years between menarche and menopause (p value = 0.009). Prolactin levels were also positively associated with increased sleep duration (p value = 0.005). The independent determinants of prolactin were years from menarche to menopause, hours of sleep, and the plasma hormones estrone and SHBG (all p values < 0.01).Conclusion: The role of prolactin in breast cancer development may involve reproductive and lifestyle factors, such as a longer duration of menstrual cycling and sleep patterns. [ABSTRACT FROM AUTHOR]

Background: Incidence of gastric cancer is the highest in Eastern Asia. Multiple modifiable lifestyle factors have been identified as risk factors for gastric cancer. However, their aggregated effect on the risk of gastric cancer has not been examined among populations with high prevalence of Helicobacter pylori.Methods: A study was conducted to examine the association between multiple lifestyle factors together and the risk of developing gastric adenocarcinoma in the Singapore Chinese Health Study, a prospective cohort of 63 257 men and women between 45 and 74 years enroled during 1993-1998. Composite score of cigarette smoking, alcohol consumption, obesity, dietary pattern, and sodium intake at baseline was assessed with hazard ratio (HR) and 95% confidence interval (CI) of gastric adenocarcinoma using Cox regression method.Results: Higher healthy composite lifestyle scores were significantly associated with reduced risk of gastric adenocarcinoma in a dose-dependent manner. Hazard ratios (95% CIs) for total, cardia, and non-cardia gastric adenocarcinoma for the highest (score 5) vs lowest composite score (score 0/1/2) were 0.42 (0.31-0.57), 0.22 (0.10-0.47), and 0.55 (0.39-0.78), respectively (all Ptrend<0.001). These lifestyles together accounted for 48% of total gastric adenocarcinoma cases in the study population. The inverse association was observed in both genders, and remained after exclusion of first 5 years of follow-up.Conclusions: The inverse association between the aggregated healthy lifestyle factors and the risk of gastric adenocarcinoma is in dose-dependent manner in this highly H. pylori-exposed population. These lifestyle factors together may account for up to half of disease burden in this study population. [ABSTRACT FROM AUTHOR]

Background: Vitamin B6 is an important enzymatic cofactor in pathways relevant for the development of pancreatic cancer. In order to evaluate vitamin B6 as a preventive factor for pancreatic cancer, a biomarker approach is needed to overcome the limitations inherent in self-reported dietary information.Methods: To determine whether levels of serum B6 vitamers, including pyridoxal 5'-phosphate (PLP), pyridoxal (PL), 4-pyridoxic acid (PA), and the PA/(PLP + PL) ratio (PAr), were associated with risk of pancreatic cancer, two nested case-control studies of 187 incident pancreatic cancer cases and 258 individually matched controls were conducted within two prospective cohorts of 81,501 participants in Shanghai, China, and Singapore. PLP, PL, and PA were quantified in pre-diagnostic serum samples. Odds ratios and 95% confidence intervals (CIs) were calculated using conditional logistic regression with adjustment for potential confounders.Results: The median (5th-95th percentiles) concentrations of serum PLP among control subjects of the Shanghai and Singapore cohorts were 25.7 (10.0-91.7) nmol/L and 58.1 (20.8-563.0) nmol/L, respectively. In pooled analyses, high serum PLP was associated with a reduced risk of pancreatic cancer (P for trend = 0.048); the adjusted odds ratio for the highest category of PLP (>52.4 nmol/L) was 0.46 (95% CI 0.23, 0.92) compared to vitamin B6 deficiency (<20 nmol/L). No associations were found for serum PL, PA, or PAr with pancreatic cancer risk.Conclusions: Higher concentrations of PLP may protect against the development of pancreatic cancer. The protective effect may be more apparent in populations with low concentrations of circulating vitamin B6. [ABSTRACT FROM AUTHOR]

Background: Green tea has been suggested to improve cardiovascular disease risk factors, including circulating lipid variables. However, current evidence is predominantly based on small, short-term randomized controlled trials conducted in diverse populations. Objective: The aim of this study was to examine the efficacy and impact of green tea extract (GTE) supplementation high in epigallocatechin gallate (EGCG) on blood lipids in healthy postmenopausal women. Design: This was an ancillary study of a double-blind, randomized, placebo-controlled, parallel-arm trial investigating the effects of a GTE supplement containing 1315 mg catechins (843 mg EGCG) on biomarkers of breast cancer risk. Participants were randomly assigned to receive GTE (n = 538) or placebo (n = 537) and were stratified by catechol-O-methyltransferase (COMT) genotype activity (high COMT compared with low or intermediate COMT genotype activity). They consumed either 4 GTE or identical placebo capsules daily for 12 mo. A total of 936 women completed this substudy. Circulating lipid panels including total cholesterol (TC), HDL cholesterol, and triglycerides were measured at baseline and at months 6 and 12. Results: Compared with placebo, 1-y supplementation with GTE capsules resulted in a significant reduction in circulating TC (-2.1% compared with 0.7%; P = 0.0004), LDL cholesterol (-4.1% compared with 0.9%; P < 0.0001) and non-HDL cholesterol (-3.1% compared with 0.4%; P = 0.0032). There was no change in HDL-cholesterol concentration, but triglyceride concentrations increased by 3.6% in the GTE group, whereas they decreased by 2.5% in the placebo group (P = 0.046). A significant reduction in TC was observed only among women with high (i.e., ≥200 mg/dL) baseline TC concentrations (P-interaction = 0.01) who consumed GTE capsules. The effect of GTE on the increase in triglycerides was mainly observed among obese women and statin users (P-interaction = 0.06). Conclusion: Supplementation with GTE significantly reduced circulating TC and LDL-cholesterol concentrations, especially in those with elevated baseline TC concentrations. This trial was registered at clinicaltrials.gov as NCT00917735. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM PUBLISHER]

Probable human carcinogens are generated during Chinese-style high-temperature cooking of meat and have been detected in the ambient air and on the meat surface. Although the inhalation of these compounds is an established risk factor for lung cancer, exposure via fried meat consumption has not yet been prospectively evaluated as a risk factor. The relationship between fried meat intake and lung cancer risk was investigated using data from a prospective cohort study among Chinese in Singapore. Lung cancer cases (n = 1130) were identified from 61 321 men and women, 70% of whom were lifetime never smokers. Proportional hazards regression methods were used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Overall, there was no association between fried meat intake and risk of all lung cancers combined. For lung adenocarcinoma, fried meat intake had a statistically significant association with increased risk. The association between fried meat intake and risk of lung adenocarcinoma became stronger when analyses were restricted to lifetime never smokers. Compared with the lowest tertile of fried meat intake, the HRs (95% CIs) for the second and third tertiles were 1.43 (0.98, 2.08) and 1.51 (1.03, 2.22), respectively (P for trend = 0.04). The positive association was present among both men and women. There was no association between fried meat intake and risk of non-adenocarcinomas of the lung. Our prospective results for fried meat intake support consumption as an important route of exposure to compounds from Chinese-style high-temperature cooking for the development of lung adenocarcinoma. [ABSTRACT FROM AUTHOR]

Vitamin D is known for maintaining Ca homeostasis and bone structure, and may also decrease susceptibility to chronic and infectious diseases. However, data on vitamin D status and its predictors among Southeast Asian populations are limited. We evaluated the distribution and determinants (genetic and environmental) of serum 25-hydroxyvitamin D (25(OH)D) concentrations among 504 middle-aged and elderly participants (aged 45–74 years) in the Singapore Chinese Health Study. Data on dietary and other lifestyle factors were collected by trained interviewers. Serum 25(OH)D concentrations and genetic polymorphisms in vitamin D metabolism pathway enzymes (cytochrome P450 (CYP) 2R1, 3A4, 27B1, 24A1; vitamin D binding protein (also known as group-specific component, GC); and vitamin D receptor) were measured using stored biospecimens. Mean 25(OH)D concentration was 68·8 nmol/l. Serum 25(OH)D concentrations were positively associated with dietary vitamin D intake, and inversely associated with hours spent sitting at work. BMI was not associated with 25(OH)D concentrations. CYP2R1 rs10741657, rs12794714, rs1993116; CYP3A4 rs2242480; and GC rs4588, rs7041, rs16847015, rs2298849 were statistically significantly associated with 25(OH)D concentrations. Individuals with the Gc2-2 haplotype (rs4588AA/rs7041TT) had statistically significantly lower 25(OH)D concentrations compared to all other Gc haplotypes (P-trend < 0·001). The majority of participants (86 %) had 25(OH)D concentrations ≥ 50 nmol/l, which is consistent with the 2011 Institute of Medicine (US) recommendation for bone health, and 32 % had concentrations of ≥ 75 nmol/l that are thought to be required for broader health effects. Dietary vitamin D intake, hours spent indoors at work and genetic variation in CYP2R1, CYP3A4 and GC are significant predictors of 25(OH)D concentrations among Singapore Chinese. [ABSTRACT FROM PUBLISHER]

Background: Coffee consumption has been associated with reduced markers of hepatic cell damage, reduced risk of chronic liver disease, and cirrhosis across a variety of populations. Data on the association between coffee consumption and risk of hepatocellular carcinoma (HCC), especially in high-risk populations, are sparse.Methods: This study examines the relationship between coffee and caffeine consumption, and the risk of developing HCC within the Singapore Chinese Health Study, a prospective cohort of 63,257 middle-aged and older Chinese men and women, a relatively high-risk population for HCC. Baseline data on coffee consumption and other dietary and lifestyle factors were collected through in-person interviews at enrollment between 1993 and 1998.Results: As of 31 December 2006, 362 cohort participants had developed HCC. High levels of coffee or caffeine consumption were associated with reduced risk of HCC (p for trend < 0.05). Compared with non-drinkers of coffee, individuals who consumed three or more cups of coffee per day experienced a statistically significant 44% reduction in risk of HCC (hazard ratio 0.56, 95% confidence interval, 0.31-1.00, p = .049) after adjustment for potential confounders and tea consumption.Conclusion: These data suggest that coffee consumption may reduce the risk of developing HCC in Chinese in Singapore. [ABSTRACT FROM AUTHOR]

Background: Incense use is an integral part of daily life in large parts of Asia. The burning of incense is a powerful producer of particulate matter and the smoke contains a multitude of well-characterized carcinogens. However, to the authors' knowledge, no convincing association has been reported between exposure to incense smoke and the development of cancer. Therefore, the relation between incense use and the risk of respiratory tract carcinomas was analyzed in a prospective cohort study.Methods: Between 1993 and 1998, a population-based cohort of 61,320 Singapore Chinese who were free of cancer and ages 45 to 74 years completed a comprehensive interview regarding living conditions and dietary and lifestyle factors. Through linkage to population-based registries, the cohort was followed through 2005 and cancer occurrence determined. The relative risk for these cancers associated with incense use was estimated using a Cox proportional hazards model.Results: A total of 325 upper respiratory tract (UPT) carcinomas and 821 lung carcinomas were observed during follow-up. Incense use was associated with a significantly increased risk of UPT carcinomas other than nasopharyngeal, whereas no overall effect was observed on lung cancer. The duration and intensity of incense use were associated with an increased risk of squamous cell carcinomas in the entire respiratory tract (P for trend = .004), whereas there was no significant association noted between incense use and nonsquamous cell carcinomas. The relative risk of squamous cell carcinomas among long-term incense users was 1.8 (95% confidence interval [95% CI], 1.2-2.6; P = .004) in the entire respiratory tract.Conclusions: The results of the current study indicate that long-term use of incense is associated with an increased risk of squamous cell carcinoma of the respiratory tract. [ABSTRACT FROM AUTHOR]

Purpose: The incidence of Endometrial cancer (EC) has grown substantially in Asia over the past decade. However, few studies have addressed risk factors associated with EC incidence in Asian populations. We explored the association between reproductive and dietary risk factors and EC in the Singapore Chinese Health Study (SCHS), one of the largest prospective cohort studies in Asia.Methods: Data were collected from 34,028 ethnically Chinese women aged 45-74 residing in Singapore, enrolled between 1993 and 1998. Baseline demographic, dietary, and reproductive factors were collected via structured questionnaires. EC cases were identified from the Singapore Cancer Registry (n = 126) up to 2010. Cox proportional hazard models were used to analyze association between EC and personal, reproductive, and dietary factors.Results: The incidence of EC in this population was 28.8 per 100,000 person-years. Regardless of menopausal status, obesity (BMI ≥ 27) was associated with increased EC risk (HR = 2.22, 95% CI 1.26-3.92), while later age at menarche was associated with decreased EC risk (HR = 0.14, 95% CI 0.04-0.46). In postmenopausal women, later age at menopause was associated with increased EC risk (HR = 2.82, 95% CI 1.24-6.43). Lifestyle and nutritional factors were not associated with risk of EC in this cohort.Conclusions: This study is one of the largest cohort studies exploring EC risk factors in Asian populations. Our study identified similarities in EC risk factors for European and Asian populations, which potentially suggests that strategies developed for EC prevention in Western populations can be potentially appropriate for the Singapore Chinese population due to risk factor similarities. [ABSTRACT FROM AUTHOR]