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Deficiencies in methyl donor status may render DNA methylation changes and DNA damage, leading to carcinogenesis. Epidemiological studies reported that higher dietary intake of choline is associated with lower risk of pancreatic cancer, but no study has examined the association of serum choline and its metabolites with risk of pancreatic cancer. Two parallel case–control studies, one nested within the Shanghai Cohort Study (129 cases and 258 controls) and the other within the Singapore Chinese Health Study (58 cases and 104 controls), were conducted to evaluate the associations of baseline serum concentrations of choline, betaine, methionine, total methyl donors (i.e., sum of choline, betaine and methionine), dimethylglycine and trimethylamine N‐oxide (TMAO) with pancreatic cancer risk. In the Shanghai cohort, odds ratios and 95% confidence intervals of pancreatic cancer for the highest quartile of choline, betaine, methionine, total methyl donors and TMAO were 0.27 (0.11–0.69), 0.57 (0.31–1.05), 0.50 (0.26–0.96), 0.37 (0.19–0.73) and 2.81 (1.37–5.76), respectively, compared to the lowest quartile. The corresponding figures in the Singapore cohort were 0.85 (0.23–3.17), 0.50 (0.17–1.45), 0.17 (0.04–0.68), 0.33 (0.10–1.16) and 1.42 (0.50–4.04). The inverse associations of methionine and total methyl donors including choline, betaine and methionine with pancreatic cancer risk in both cohorts support that DNA repair and methylation play an important role against the development of pancreatic cancer. In the Shanghai cohort, TMAO, a gut microbiota‐derived metabolite of dietary phosphatidylcholine, may contribute to higher risk of pancreatic cancer, suggesting a modifying role of gut microbiota in the dietary choline‐pancreatic cancer risk association. What's new? Over half of all pancreatic cancers aren't associated with known risk factors. In this prospective study, the authors examined serum levels of three nutrients (choline, methionine, and betaine) that have been associated with reduced oxidative DNA damage and epigenetic changes such as methylation. They found that, as predicted, higher serum levels of these nutrients were correlated with lower pancreatic cancer risk. They also found that certain compounds associated with gut microbiota increased this risk. These results identify novel etiological factors that may guide future prevention strategies for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Extreme telomere length has been previously reported to be associated with increased risk of gastric cancer. However, evidence from prospective studies on a relative large sample size with long-term follow-up to further corroborate previous study findings is meager.Methods: The association between peripheral blood leukocyte telomere length and risk of gastric adenocarcinoma was prospectively examined in a cohort of 26,540 middle-aged or older Chinese nested in the Singapore Chinese Health Study. Telomere length was determined using a validated qPCR-based method. The Cox proportional regression method was used to estimate hazard ratio (HR) and its 95% confidence interval (CI) of gastric adenocarcinoma associated with telomere length after adjustment for potential confounders. Restricted cubic spline analysis was applied to assess the nonlinear relationship between telomere length and gastric cancer risk.Results: A U-shaped association was found between telomere length and risk of gastric adenocarcinoma (Pnonlinearity = 0.020). Compared with the second quintile of telomere length, a statistically significant higher risk of gastric adenocarcinoma was associated with either the lowest quintile (HR = 1.63, 95% CI, 1.07-2.47) or the highest quintile (HR = 1.55, 95% CI, 0.97-2.47) of telomere length. This U-shaped relationship was more apparent in men and younger individuals.Conclusions: This is the first prospective study demonstrating a higher risk of gastric cancer to be associated with either extremely short or extremely long telomere length. Short and long telomere length may function differently in the early and late stages of gastric carcinogenesis. [ABSTRACT FROM AUTHOR]

It has been hypothesized that the pathogenesis of lung cancer induced by cigarette smoking involves oxidative damage by free radicals. Epidemiological data on biomarkers of oxidative damage and risk of lung cancer development are sparse. A nested case-control study of 610 lung cancer cases and 610 matched controls was conducted within a prospective cohort of 18 244 Chinese men in Shanghai, China. The concentrations of 8-epi-prostaglandin F2 (8-epiPGF2), a biomarker of oxidative stress, were determined in baseline urine samples using a validated mass-spectrometry assay. Current smokers had significantly higher level of 8-epiPGF2 than former smokers or never smokers (P < 0.001). 8-epiPGF2 levels were significantly higher in lung cancer cases than their smoking-matched controls in former and current smokers, but not different in never smokers (P for interaction = 0.019). The relative risks of developing lung cancer for former and current smokers in the highest relative to the lowest quartile of 8-epiPGF2 were 5.25 (P trend = 0.035) and 1.99 (P trend =0.007), respectively. The effect of 8-epiPGF2 and biomarkers of cigarette smoke exposure on lung cancer risk was additive; the relative risk was 5.33 (95% confidence interval = 2.65-7.51) for current smokers with the highest thirds of 8-epiPGF2 and total cotinine compared with their lowest thirds. Smokers with a heightened state of oxidative stress in response to the insults of cigarette smoking may be more susceptible to smoking-induced lung carcinogenesis. [ABSTRACT FROM AUTHOR]

ABO blood type is an inherited characteristic. The associations between ABO blood type and risk of all cancer and specific cancers were examined in a prospective cohort study of 18,244 Chinese men enrolled in 1986. During the 25 years of follow-up, 3,973 men developed cancer including 964 lung cancers, 624 colorectal cancers, 560 gastric cancers, 353 liver cancers, and 172 urinary bladder cancers. Hazard ratios (HR) for all cancer and specific cancers by ABO blood type were calculated using Cox proportional hazards models. Compared with blood type A, blood type B was associated with statistically significant reduced risk of all cancers (HR, 0.91, 95% CI:0.84, 0.99). Both blood types B and AB were associated with significantly lower risk of gastrointestinal cancer and colorectal cancer, respectively. Blood type B was also associated with significantly lower risk of stomach cancer and bladder cancer, while blood type AB was associated with significantly increased risk of liver cancer. By histological type, blood types B and AB were associated with lower risk of epidermoid carcinoma and adenocarcinoma, but were not associated with risk of sarcoma, lymphoma, leukemia or other cell types of cancer. The findings of this study support a role of genetic traits related to ABO blood type in the development of cancers in the gastrointestinal and urinary tracts. [ABSTRACT FROM AUTHOR]

Background & Aim Lipidomic signature of lipid metabolism suggests that omega-6 polyunsaturated fatty acids ( PUFA) may play a role in oncogenesis of hepatocellular carcinoma ( HCC). Hence, we examined the association between dietary fatty acids and risk of HCC. Methods We used data from the Singapore Chinese Health Study, a population-based prospective cohort of 63 257 Chinese men and women aged 45-74 years enrolled between 1993 and 1998. Information on current diet assessed via a validated semi-quantitative food frequency questionnaire, medical history and lifestyle factors were obtained through in-person interview, and incidence of HCC recorded through 31 Dec 2010. We also examined the association between dietary fatty acids and HCC risk using a case-control set of 92 cases and 274 controls with available serological biomarkers of chronic infections with hepatitis B virus ( HBV) and hepatitis C virus ( HCV) nested within this cohort. Results Among the dietary fat components examined, which included saturated, monounsaturated, omega-3 and omega-6 PUFA, only omega-6 PUFA intake displayed a dose-dependent, positive association with HCC risk (p for trend = 0.02). Compared to the lowest quartile, the hazard ratio for the highest quartile intake was 1.49 [(95% confidence interval ( CI):1.08-2.07)]. In the nested case-control study, only among individuals negative for serology markers of chronic infection with HBV or HCV, those who consumed above median levels of dietary omega-6 PUFA had increased HCC risk (odds ratio = 4.36, 95% CI = 1.59-11.94) compared to those with lower intake. Conclusion Dietary omega-6 PUFA may be implicated in the risk of non-viral hepatitis related HCC. [ABSTRACT FROM AUTHOR]

Background: N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. Methods: A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Results: Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76–14.04) and 4.82 (95% confidence interval = 1.05–22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. Conclusion: The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection. [ABSTRACT FROM AUTHOR]

N′-Nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) are tobacco-specific nitrosamines. NNN and NNK can induce cancers of the esophagus and lung, respectively, in laboratory animals, but data on human esophageal cancer are lacking. The association between levels of NNN and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), an NNK metabolite, in urine samples collected before diagnosis and risk of esophageal cancer was examined in 77 patients with esophageal cancer and 223 individually matched controls, all current smokers, from a cohort of 18244 Chinese men in Shanghai, China, followed from 1986 to 2008. Urinary total NNN (free NNN plus NNN-N-glucuronide) was significantly higher, whereas the percentage of its detoxification product NNN-N-glucuronide was significantly lower in cases than controls. Odds ratios (95% confidence intervals) of esophageal cancer for the second and third tertiles of total NNN were 3.99 (1.25–12.7) and 17.0 (3.99–72.8), respectively, compared with the first tertile after adjustment for urinary total NNAL and total cotinine and smoking intensity and duration (Ptrend < 0.001). The corresponding figures for the percentage of NNN-N-glucuronides were 0.37 (0.17–0.80) and 0.27 (0.11–0.62) (Ptrend = 0.001). Urinary total NNN and the percentage of NNN-N-glucuronides almost completely accounted for the observed association for urinary total NNAL (free NNAL plus its glucuronides), urinary total cotinine and smoking intensity with esophageal cancer risk. These findings along with results of previous studies in laboratory animals support a significant and unique role of NNN in esophageal carcinogenesis in humans. [ABSTRACT FROM AUTHOR]

Background: The occurrence of diabetes has greatly increased in low- and middle-income countries, particularly in Asia, as has the prevalence of overweight and obesity; in European-derived populations, overweight and obesity are established causes of diabetes. The shape of the association of overweight and obesity with diabetes risk and its overall impact have not been adequately studied in Asia. Methods and Findings: A pooled cross-sectional analysis was conducted to evaluate the association between baseline body mass index (BMI, measured as weight in kg divided by the square of height in m) and self-reported diabetes status in over 900,000 individuals recruited in 18 cohorts from Bangladesh, China, India, Japan, Korea, Singapore and Taiwan. Logistic regression models were fitted to calculate cohort-specific odds ratios (OR) of diabetes for categories of increasing BMI, after adjustment for potential confounding factors. OR were pooled across cohorts using a random-effects meta-analysis. The sex- and age-adjusted prevalence of diabetes was 4.3% in the overall population, ranging from 0.5% to 8.2% across participating cohorts. Using the category 22.5-24.9 Kg/m2 as reference, the OR for diabetes spanned from 0.58 (95% confidence interval [CI] 0.31, 0.76) for BMI lower than 15.0 kg/m2 to 2.23 (95% CI 1.86, 2.67) for BMI higher than 34.9 kg/m2. The positive association between BMI and diabetes prevalence was present in all cohorts and in all subgroups of the study population, although the association was stronger in individuals below age 50 at baseline (p-value of interaction<0.001), in cohorts from India and Bangladesh (p<0.001), in individuals with low education (p-value 0.02), and in smokers (p-value 0.03); no differences were observed by gender, urban residence, or alcohol drinking. Conclusions: This study estimated the shape and the strength of the association between BMI and prevalence of diabetes in Asian populations and identified patterns of the association by age, country, and other risk factors for diabetes. [ABSTRACT FROM AUTHOR]

Prospective data on environmental exposures, especially with respect to alcohol, tobacco, and diet, in relation to the risk of esophageal cancer in high-risk populations are sparse. We analyzed data from a population-based cohort of 18,244 middle-aged and older men in Shanghai to identify risk factors for esophageal cancer in this high-risk population. The cohort was followed through 2006, and 101 incident esophageal cancer cases were identified. Cox proportional hazards models were used to estimate hazard ratios (HR) and their corresponding 95% confidence intervals (CI) for associations between exposures and esophageal cancer risk. With adjustment for tobacco use and other potential confounders, regular drinkers vs. nondrinkers of alcoholic beverages had a twofold risk of developing esophageal cancer (HR = 2.02, 95% CI = 1.31-3.12). With adjustment for alcohol and other potential confounders, long-term smokers (40+ yr) vs. nonsmokers of cigarettes showed a twofold risk of developing esophageal cancer (HR = 2.06, 95% CI = 1.11-3.82). Increased consumption of fruits (including oranges/tangerines), seafood, and milk were found to be protective against the development of esophageal cancer; HRs were decreased by 40-60% for high vs. low consumers after adjustment for cigarette smoking, alcohol drinking, and other confounders. [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]