Although there is some epidemiologic evidence that soy may reduce risk of osteoporotic fracture in women, it is not known whether this risk reduction also occurs for men. The authors examined gender-specific associations between soy intake and hip fracture risk in the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese living in Singapore. At recruitment between 1993 and 1998, each subject was administered a food frequency questionnaire and questions on medical history and lifestyle factors. As of December 31, 2006, 276 incident cases of hip fracture in men and 692 cases in women were identified via linkage with hospital discharge databases. For both genders, hip fracture risk was positively associated with cigarette smoking and was inversely associated with body mass index. There was a statistically significant association of tofu equivalents, soy protein, and isoflavones with hip fracture risk among women but not among men. Compared with women in the lowest quartile of intakes for tofu equivalents (<49.4 g/day), soy protein (<2.7 g/day), and isoflavones (<5.8 mg/1,000 kcal/day), those in the second–fourth quartiles exhibited 21%–36% reductions in risk (all P < 0.036). Risk levels were comparable across the second, third, and fourth quartiles of soy intake categories.
Asian Continental Ancestry Group; hip fractures; isoflavones; osteoporosis; soy foods
While some studies have found a positive association between both short and long sleep durations and cardiovascular disease (CVD), others have found an association only with a long or short sleep duration. In addition, there are limited data from non-Western populations on this topic. The authors examined the association between sleep duration and coronary heart disease (CHD) mortality among Chinese adults in Singapore (1993-2006), performing a prospective cohort study among 58,044 participants aged ≥45 years (55.9% women) without preexisting CVD. The main outcome of interest was CHD mortality (n = 1,416). The authors found both short and long sleep durations to be positively associated with CHD mortality, independent of smoking, alcohol intake, and body mass index. Compared with persons with a sleep duration of 7 hours (referent), the multivariable relative risk of CHD mortality for a sleep duration of ≤5 hours was 1.57 (95% confidence interval: 1.32, 1.88); for a sleep duration of ≥9 hours, it was 1.79 (95% confidence interval: 1.48, 2.17). This association persisted in subgroup analyses by sex sleep and body mass index. In a population-based cohort of Chinese adults from Singapore, sleep durations of ≤5 hours and ≥9 hours (versus 7 hours) were modestly associated with CHD mortality. These results suggest that duration may be an important marker for CVD.
Asian continental ancestry group; cardiovascular diseases; coronary disease; mortality; Singapore; sleep
We previously reported an inverse association between sleep duration and breast cancer risk in the prospective, population-based Singapore Chinese Health Study (SCHS) cohort (Wu et al., Carcinogenesis 2008;29:1244–8). Sleep duration was significantly positively associated with 6-sulfatoxymelatonin (aMT6s) levels determined in a spot urine, but aMT6s levels in breast cancer cases were lacking (Wu et al., Carcinogenesis 2008;29:1244–8). We updated the sleep duration–breast cancer association with 14 years of follow-up of 34,028 women in the SCHS. In a nested case–control study conducted within the SCHS, randomly timed, prediagnostic urinary aMT6s concentrations were compared between 248 incident breast cancer and 743 individually matched cohort controls. Three female controls were individually matched to each case on age at baseline interview (within 3 years), dialect group, menopausal status, date of baseline interview (within 2 years), date of urine sample collection (within 6 months) and timing of urine collection during the day (within 1 hr). Cox proportional hazards and conditional regression models with appropriate adjustment for confounders were used to examine the sleep– and aMT6s–breast cancer relationships. Breast cancer risk was not significantly associated with sleep duration; adjusted odds ratio (OR) for 9+ vs. ≤6 hr is 0.89 [95% confidence interval (95% CI) 5 0.64–1.22]. Prediagnostic aMT6s levels did not differ between breast cancer cases and matched controls; adjusted OR for highest versus lowest quartiles is 1.00 (95% CI 5 0.64-1.54). We conclude that sleep duration is not significantly associated with breast cancer risk reduction. Melatonin levels derived from randomly timed spot urine are unrelated to breast cancer. Randomly timed, spot urine-derived melatonin levels are noninformative as surrogates of nocturnal melatonin production.
sleep duration; spot urinary melatonin; breast cancer; prospective; Singaporean Chinese
The enzymes folylpolyglutamate synthase (FPGS) and gamma-glutamyl hydrolase (GGH) are essential for determining intracellular folate availability for one-carbon metabolism (OCM) pathways. FPGS adds glutamyl groups to the folate molecule, thereby converting folate into the preferred substrate for several enzymes in OCM pathways. GGH removes glutamyl groups, allowing folate metabolites to leave the cell. The purpose of this study was to evaluate whether single nucleotide polymorphisms (SNPs) in the FPGS and GGH genes influence measured plasma homocysteine levels. Study participants were a sub-cohort (n = 482) from the Singapore Chinese Health Study. SNPs were selected using HapMap tagSNPs and SNPs previously reported in the scientific literature. Multiple linear regression was used to evaluate the association between individual SNPs and plasma homocysteine levels. Two FPGS (rs10106, rs1098774) and 9 GGH (rs719235, rs1031552, rs1800909, rs3758149, rs3780126, rs3824333, rs4617146, rs11545076, rs11545078) SNPs were included in the final analysis. Neither of the FPGS SNPs, but three GGH SNPs were associated with plasma homocysteine levels: rs11545076 (p=0.001), rs1800909 (p=0.02), and rs3758149 (p = 0.006). Only one (rs11545076) remained statistically significant after adjusting for multiple comparisons. This study suggests that GGH SNPs, rs11545076, rs1800909, and rs3758149, may have functional relevance and result in alterations in plasma homocysteine levels. Since this is one of the first studies to assess FPGS and GGH genetic variants in relation to plasma homocysteine, further research is needed to confirm these findings and characterize the functional effects of these variants.
FPGS; GGH; Folate; Homocysteine; SNP
Cigarette smoking is a risk factor for colorectal cancer. Putative colorectal procarcinogens in tobacco smoke include polycyclic aromatic hydrocarbons and heterocyclic aromatic amines that are known substrates of glutathione S-transferases (GSTs). This study examined the influence of functional GST gene polymorphisms on the smoking–colorectal cancer association in a population known to be minimally exposed to dietary sources of these procarcinogens. Incident cases of colorectal cancer (n = 480) and matched controls (n = 1167) were selected from the Singapore Chinese Health Study, a population-based prospective cohort of 63 257 men and women who have been followed since 1993. We determined the deletion polymorphisms of GSTM1 and GSTT1 and the functional polymorphism at codon 105 of GSTP1 for each subject. A three level composite GST index was used to examine if GST profile affected a smoker’s risk of developing colorectal cancer. While there was no statistically significant association between cigarette smoking and colorectal cancer risk among subjects absent of any at-risk GST genotypes, smokers possessing two to three at-risk GST genotypes exhibited a statistically significant increased risk of colorectal cancer compared with non-smokers (P = 0.0002). In this latter stratum, heavy smokers exhibited a >5-fold increased risk relative to never-smokers (odds ratio, 5.43; 95% confidence interval, 2.22–13.23). Subjects with one at-risk GST genotype displayed a statistically significant but weaker association with smoking. These findings suggest that GST gene polymorphisms influence interindividual susceptibility to smoking-associated colorectal cancer. Our data indicate an important role for GST enzymes in the detoxification of colorectal carcinogens in tobacco smoke.
Mitochondria are eukaryotic organelles responsible for energy production. Quantitative changes in human mitochondrial DNA (mtDNA) copy number have been implicated in various cancer types. Data from prospective cohort studies on mtDNA copy number and colorectal cancer risk have been lacking.
We evaluated the association between mtDNA copy number in peripheral blood and colorectal cancer risk in a nested case-control study of 422 colorectal cancer cases (168 cases with pre-diagnostic blood and 254 cases with post-diagnostic blood) and 874 controls who were free of colorectal cancer among participants of the Singapore Chinese Health Study. The relative mtDNA copy number was measured using real time PCR. Unconditional logistic regression methods were employed to examine the association between mtDNA copy number and colorectal cancer risk.
There was a U-shaped relationship between the relative mtDNA copy number and colorectal cancer risk. Compared with the 2nd quartile, the odds ratios (95% confidence intervals) for subjects in the lowest and highest quartiles of relative mtDNA copy numbers were 1.81 (1.13–2.89) and 3.40 (2.15–5.36), respectively (Pcurvilinearity <0.0001). This U-shaped relationship was present in both men and women, similar for colon cancer and rectal cancer, and independent of the timing of blood draw with regards to cancer diagnosis.
This is the first prospectively designed study to show a U-shaped association between the relative mtDNA copy number and risk of colorectal cancer.
The findings of the present study support that mtDNA may play a critical role in the colorectal carcinogenesis in humans.
Mitochondria; colorectal cancer; prospective; cohort; mitochondrial DNA copy number
Modification of low density lipoprotein due to oxidative stress is essential in the development of coronary atherosclerosis. Data of specific carotenoids except β-carotene on cardioprotective effects in humans are limited.
Objective and methods
This study examined the associations between plasma concentrations of specific carotenoids and incidence of acute myocardial infarction. The study included 280 incident cases of acute myocardial infarction and 560 matched controls nested within the Singapore Chinese Health Study, a prospective cohort of 63,257 Chinese men and women aged 45 to 74 years old enrolled in 1993-1998 in Singapore. Retinol and carotenoids in prediagnostic plasma were quantified using high-performance liquid chromatography.
High levels of plasma β-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction after adjustment for multiple risk factors for coronary heart disease. For β-cryptoxanthin, the odds ratio (95% confidence interval) for the highest (Q5) versus the lowest (Q1) quintile was 0.67 (0.37-1.21) (P for trend = 0.03). For lutein, the odds ratios (95% confidence intervals) for Q2-Q3 and Q4-Q5 versus Q1 were 0.71 (0.45-1.12) and 0.58 (0.35-0.94) respectively (P for trend = 0.03). There was no statistically significant association between other carotenoids or retinol and risk of acute myocardial infarction.
High plasma levels of β-cryptoxanthin and lutein were associated with decreased risk of acute myocardial infarction. The findings of this study support a cardioprotective role of these two carotenoids in humans.
antioxidants; carotenoids; coronary disease; nested case-control study; Chinese
To examine the association between body mass index (BMI) and incident colorectal cancer across the spectrum of BMI, including underweight, because detailed prospective cohort data on this topic in Asians is scarce, as is data on underweight (BMI < 18.5 kg/m2) in any population
RESEARCH DESIGN AND METHODS
Analysis of the Singapore Chinese Health Study included 51,251 men and women ages 45–74 years enrolled in 1993–1998 and followed up through 2007. Incident cancer cases and deaths among cohort members were identified through record linkage and 980 cases were identified. Cox regression models were used to investigate the association of baseline BMI with risk of incident colorectal cancer during mean 11.5 years of follow-up.
A significant U-shaped, quadratic association was observed between BMI and colon cancer risk, with increased risk in BMI’s ≥27.5 and < 18.5 kg/m2. The association was more pronounced in never-smokers; and most prominent when further limiting the sample to those free of diabetes and cases with greater than five years of follow up. Localized cases had a more pronounced association in BMI’s ≥27.5, whereas advanced cases had a more pronounced association in BMI’s < 18.5 kg/m2. No association was found in relation to rectal cancer risk. The association was also stronger among subjects aged 65 years and above.
BMI displays a U-shaped, quadratic association with colon cancer risk in this Chinese population in Southeast Asia.
Body mass index; obesity; underweight; Asians; colorectal cancer
Experimental studies suggest that sex hormones may induce or promote the development of hepatocellular carcinoma (HCC). Androgens are converted to estrogens by the CYP19 gene product, aromatase. Hepatic aromatase level and activity have been shown to be markedly elevated in HCC. Aromatase expression in liver tumors is driven by a promoter upstream of CYP19 exon I.6.
We first identified an A/C polymorphism in the exon I.6 promoter of the CYP19 gene. To determine whether allelic variants in the CYP19 I.6 promoter differ in their ability to drive gene expression, we carried out an in-vitro reporter gene assay. We then studied the association between this polymorphism and HCC risk in two complementary case-control studies: one in high-risk southern Guangxi, China, and another in low-risk US non-Asians of Los Angeles County.
Transcriptional activity was 60% higher for promoter vectors carrying the rs10459592 C allele compared to those carrying an A allele (p=0.007). In both study populations, among subjects negative for at-risk serologic markers of hepatitis B or C, there was a dose-dependent association between number of high activity C allele and risk of HCC (p for trend=0.014). Risk of HCC was significantly higher [odds ratio (OR) = 2.25, 95% confidence interval (CI) = 1.18–4.31] in subjects homozygous for the C allele compared to those homozygous for the A allele.
Our study provides epidemiologic evidence for the role of hepatic aromatization of androgen into estrogen in the development of non-viral hepatitis-related HCC.
Aromatase enzyme; hepatocellular carcinoma; gene polymorphism; viral hepatitis; sex hormones
We prospectively investigated whether coffee consumption was associated with decreased risk of colorectal cancer and whether cigarette smoking and stage of disease modify the association in the Singapore Chinese Health Study. During the first 12 years of follow-up, 961 colorectal cancer cases occurred in the cohort of over 60,000 middle-aged or older Chinese men and women living in Singapore. Baseline dietary exposures were assessed through in-person interviews using a validated food frequency questionnaire. The relation between coffee consumption and colorectal cancer risk was assessed by proportional hazards (Cox) regression. No overall association between coffee intake and colorectal cancer was observed. However, in analysis by subsite and stage restricted to ever smokers, the coffee–colon cancer association became statistically significant for advanced disease (P for trend = 0.01). The hazard ratio was 0.56 (95% confidence interval = 0.35–0.90) for advanced colon cancer in drinkers of 2 or more cups per day compared with those who drank no coffee or less than 1 cup per day. Although there is a null association between coffee intake and risk of colorectal cancer overall, coffee may protect against smoking related advanced colon cancer.
The MDM2 oncoprotein regulates the p53 pathway and, while functional polymorphisms of the MDM2 and p53 genes have been investigated for association with breast cancer risk, results are largely null or non-conclusive. We have earlier reported that the increased intake of soy isoflavones reduces risk of postmenopausal breast cancer, and experimental studies suggest that dietary isoflavones can down-regulate the expression of the MDM2 oncoprotein. In this study, we investigated the association between the MDM2 SNP309 and TP53 R72P polymorphisms and breast cancer risk using a case–control study of 403 cases and 662 controls nested among 35,303 women in The Singapore Chinese Health Study, a population-based, prospective cohort of middle-aged and elderly men and women who have been continuously followed since 1993. The G allele of the TP53 R72P polymorphism and T allele of the MDM2 SNP309 polymorphism were putative high-risk alleles and exhibited a combined gene–dose-dependent joint effect on breast cancer risk that was more clearly observed in postmenopausal women. Among postmenopausal women, the simultaneous presence of G allele in TP53 and T allele in MDM2 polymorphisms was associated with an odds ratio (OR) of 2.42 [95% confidence interval (CI) 1.06–5.50]. Furthermore, the protective effect of dietary soy isoflavones on postmenopausal breast cancer was mainly confined to women homozygous for the high activity MDM2 allele (GG genotype). In this genetic subgroup, women consuming levels of soy isoflavones above the median level exhibited risk that was half of those with below median intake (OR 0.52; 95% CI 0.28–0.99). Our findings support experimental data implicating combined effects of MDM2 protein and the p53-mediated pathway in breast carcinogenesis, and suggest that soy isoflavones may exert protective effect via down-regulation of the MDM2 protein.
MDM2; p53; Soy isoflavones; Breast cancer; Chinese
Sugar-sweetened carbonated beverages (called soft drinks) and juices, which have a high glycemic load relative to other foods and beverages, have been hypothesized as pancreatic cancer risk factors. However, data thus far are scarce, especially from non-European descent populations. We investigated whether higher consumption of soft drinks and juice increases the risk of pancreatic cancer in Chinese men and women.
A prospective cohort analysis was done to examine the association between soft drink and juice consumption and the risk of pancreatic cancer in 60,524 participants of the Singapore Chinese Health Study with up to 14 years of follow-up. Information on consumption of soft drinks, juice, and other dietary items, as well as lifestyle and environmental exposures, was collected through in-person interviews at recruitment. Pancreatic cancer cases and deaths were ascertained by record linkage of the cohort database with records of population-based Singapore Cancer Registry and the Singapore Registry of Births and Deaths.
The first 14 years for the cohort resulted in cumulative 648,387 person-years and 140 incident pancreatic cancer cases. Individuals consuming ≥2 soft drinks/wk experienced a statistically significant increased risk of pancreatic cancer (hazard ratio, 1.87; 95% confidence interval, 1.10–3.15) compared with individuals who did not consume soft drinks after adjustment for potential confounders. There was no statistically significant association between juice consumption and risk of pancreatic cancer.
Regular consumption of soft drinks may play an independent role in the development of pancreatic cancer.
Lifestyle factors directly influence cardiovascular disease (CVD) risk, yet little research has examined the association of combined lifestyle factors with CVD mortality, especially in Asian populations.
Methods and Results
We examined the association of 6 combined lifestyle factors (dietary pattern, physical activity, alcohol intake, usual sleep, smoking status, and body mass index) with CVD mortality in 50 466 (44 056 without a history of diabetes mellitus, CVD, or cancer and 6410 with diabetes mellitus or history of clinical CVD) Chinese men and women in Singapore who were 45 to 74 years of age during enrollment in the Singapore Chinese Health Study in 1993 to 1998 and followed up through 2009. Each lifestyle factor was independently associated with CVD mortality. When combined, there was a strong, monotonic decrease in age- and sex-standardized CVD mortality rates with an increasing number of protective lifestyle factors. Relative to participants with no protective lifestyle factors, the hazard ratios of CVD mortality for 1, 2, 3, 4, and 5 to 6 protective lifestyle factors were 0.60 (95% confidence interval, 0.45-0.84), 0.50 (95% confidence interval, 0.38-0.67), 0.40 (95% confidence interval, 0.30-0.53), 0.32 (95% confidence interval, 0.24-0.43), and 0.24 (95% confidence interval, 0.17-0.34), respectively, among those without a history of diabetes mellitus, CVD, or cancer (P for trend <0.0001). A parallel graded inverse association was observed in participants with a history of CVD or diabetes mellitus at baseline. Results were consistent for coronary heart disease and cerebrovascular disease mortality.
An increasing number of protective lifestyle factors is associated with a marked decreased risk of coronary heart disease, cerebrovascular disease, and overall CVD mortality in Chinese men and women.
Asian continental ancestry group; cardiovascular disease; life style; mortality; risk factors
Whether the link between gout and mortality is causal or confounded by lifestyle factors or comorbidities remains unclear. Studies in Asia are warranted due to the rapid modernisation of the locale and ageing of the population.
The association between gout and mortality was examined in a prospective cohort, the Singapore Chinese Health Study, comprising 63 257 Singapore Chinese individuals, aged 45–74 years during the enrolment period of 1993–8. All enrollees were interviewed in person on lifestyle factors, current diet and medical histories. All surviving cohort members were contacted by telephone during 1999–2004 to update selected exposure and medical histories (follow-up I interview), including the history of physician-diagnosed gout. Cause-specific mortality in the cohort was identified via record linkage with the nationwide death registry, up to 31 December 2009.
Out of 52 322 participants in the follow-up I interview, 2117 (4.1%) self-reported a history of physician-diagnosed gout, with a mean age at diagnosis of 54.7 years. After a mean follow-up period of 8.1 years, there were 6660 deaths. Relative to non-gout subjects, subjects with gout had a higher risk of death (HR 1.18; 95% CI 1.06 to 1.32), and specifi cally from death due to coronary heart disease (CHD) (HR 1.38, 95% CI 1.10 to 1.73) and kidney disease (HR 5.81, 95% CI 3.61 to 9.37). All gout–mortality risk associations were present in both genders but the risk estimates appeared higher for women.
Gout is an independent risk factor for mortality, and specifically for death due to CHD and kidney disease.
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.
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 inperson interviews at enrollment between 1993 and 1998.
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.
These data suggest that coffee consumption may reduce the risk of developing HCC in Chinese in Singapore.
Coffee; Caffeine; HCC; Hepatocellular; Liver cancer; GGT
Nutrigenetics and nutrigenomics hold much promise for providing better nutritional advice to the public generally, genetic subgroups and individuals. Because nutrigenetics and nutrigenomics require a deep understanding of nutrition, genetics and biochemistry and ever new ‘omic’ technologies, it is often difficult, even for educated professionals, to appreciate their relevance to the practice of preventive approaches for optimising health, delaying onset of disease and diminishing its severity. This review discusses (i) the basic concepts, technical terms and technology involved in nutrigenetics and nutrigenomics; (ii) how this emerging knowledge can be applied to optimise health, prevent and treat diseases; (iii) how to read, understand and interpret nutrigenetic and nutrigenomic research results, and (iv) how this knowledge may potentially transform nutrition and dietetic practice, and the implications of such a transformation. This is in effect an up-to-date overview of the various aspects of nutrigenetics and nutrigenomics relevant to health practitioners who are seeking a better understanding of this new frontier in nutrition research and its potential application to dietetic practice.
Dietetics; Nutrigenetics; Nutrigenomics; Nutrition Research; Personalised nutrition
A seroepidemiologic study using the microimmunofluorescence (MIF) technique was conducted to determine the prevalence of Chlamydophila pneumoniae IgG antibodies among 205 healthy Singapore university undergraduates using the MRL Diagnostics MIF test kit. The overall seroprevalence was 35.1% with significantly higher seropositivity rates among males than females (48.2 vs. 18.7%, P < 0.001). A comparative study using the Labsystems MIF test kit was conducted on sera from 192 students. Using the MRL MIF test as the reference, the sensitivity and specificity of Labsystems MIF test were 92.6 and 87.9%, respectively. A total of 78 samples comprising 15 MIF-negative and 63 MIF-positive samples were also tested for complement-independent neutralizing antibodies in vitro. All the 78 samples and 11 additional MIF-negative samples were also tested for IgM, IgG and IgA against C. pneumoniae by enzyme immunoassay (EIA) using the Labsystems EIA test kit. None of these 89 samples were seropositive for IgM. The percentages of IgG and IgA seropositivity increased with increasing grades of MIF-positivity. Among the IgG seropositive samples, 69.1% were also positive for IgA, suggesting that a high proportion of infected individuals also had IgA antibodies denoting chronicity. Neutralizing antibodies were detected in 22.2% of MIF-positive sera, but only in 6.7% of MIF-negative sera. 26.4 and 34.2% of samples which were IgG and IgA seropositive respectively also exhibited neutralizing activity. The percentages of MIF-positive sera with neutralizing activity increased with the grade of MIF positivity, i.e. 0% (1+), 7.1% (2+), 18.8% (3+), and 63.6% (4+). High-grade MIF positivity (particularly with MRL MIF kits) may represent a useful serologic marker of predictive value for neutralizing activity.
Chlamydophila pneumoniae; Microimmunofluorescence; Enzyme immunoassay; Neutralization test; Seroepidemiology
S-adenosylmethionine (SAM) is a primary methyl donor for the methylation of many molecules including DNA. DNA methylation is believed to play an important role in functions of cells and genes. Dietary, genetic and metabolic factors that influence systematic SAM levels are not fully understood. We conducted cross-sectional analysis to evaluate associations between plasma concentrations of one-carbon metabolism nutrients and metabolites and plasma SAM concentrations using healthy individuals within the Singapore Chinese Health Study. Plasma SAM, betaine, choline, folate, total homocysteine (Hcy), methionine, S-adenosylhomocysteine (SAH), vitamin B6 and vitamin B12 concentrations were quantified. Genotypes of methionine adenosyltransferases (MAT1A, MAT2A and MAT2B) were also determined. Linear regression and path analysis were performed to depict the directed dependencies in one-carbon metabolism. Age and body mass index were positively associated while cigarette smoking were inversely associated with plasma SAM concentrations. Plasma choline, methionine and SAH were positively and strongly associated with plasma SAM after adjustment for confounders. Plasma betaine and folate were positively associated with plasma SAM only in men. Men carrying the variant MAT1A genotypes had lower plasma SAM concentrations than men carrying the wild type genotype (p for gene x gender interaction = 0.02). This effect modification by gender was restricted to individuals with low plasma methionine. In conclusion, plasma choline, methionine and SAH were strongly associated with plasma SAM concentrations. The MAT1A genetic polymorphism may impact plasma SAM concentrations in men with low plasma methionine concentrations.
One-carbon metabolism; plasma SAM; MAT genetic polymorphism; path analysis
To empirically derive dietary patterns and examine their association with incident type 2 diabetes.
RESEARCH DESIGN AND METHODS
We used data from the Singapore Chinese Health Study, including 43,176 Chinese men and women (aged 45–74 years), free of diabetes, cardiovascular disease, and cancer at baseline (1993–1998) and followed up through 2004. Two major dietary patterns were identified using principal components analysis: a vegetable, fruit, and soy-rich pattern (VFS) and a dim sum and meat-rich pattern (DSM). Pattern scores for each participant were calculated and examined with type 2 diabetes risk using Cox regression.
The associations of the two dietary patterns with diabetes risk were modified by smoking status. Neither pattern was associated with risk of diabetes in ever smokers. In never smokers, the VFS dietary pattern was inversely associated with risk of type 2 diabetes. Compared with the lowest quintile of the VFS dietary pattern score, the hazard ratios (HRs) for quintiles 2–5 were 0.91, 0.82, 0.73, and 0.75 (P = 0.0005 for trend). The DSM dietary pattern was positively associated with risk of type 2 diabetes in never smokers, with HRs for quintiles 2–5 of 1.07, 1.25, 1.18, and 1.47 (P < 0.0001 for trend).
A dietary pattern with higher intake of vegetables, fruits, and soy foods was inversely associated with risk of incident type 2 diabetes, and a pattern with higher intake of dim sum, meat and processed meat, sweetened foods and beverages, and fried foods was associated with a significantly increased risk of type 2 diabetes in Chinese men and women in Singapore.
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).
Colorectal cancer, Singapore; PARP; Polyunsaturated fatty acids; n–3 Polyunsaturated fatty acids
Asian populations are documenting rapid increases in the rates of diabetes and hip fracture, but there are no prospective data linking both diseases in Asian studies. We investigated this association among a cohort of Chinese in Singapore.
RESEARCH DESIGN AND METHODS
A prospective cohort of 63,257 Chinese in the Singapore Chinese Health Study, established between 1993 and 1998, was followed up for a mean duration of 12 years. Diabetes status was ascertained by baseline interviews, and incidence of hip fracture post-enrollment was identified through a nationwide hospital discharge database.
The risk of hip fracture, after adjustment for other risk factors, was almost double among people with diabetes compared with people without diabetes (relative risk 1.98, 95% CI 1.71–2.29). When stratified by BMI, the increase in risk of hip fracture among people with diabetes relative to people without diabetes was similar in all four strata. There was a very strong dose-dependent relationship between duration of diabetes and risk of hip fracture (P for trend <0.0001). Compared with people without diabetes, the relative risk (95% CI) among subjects with diabetes for <5 years at recruitment was 1.40 (1.08–1.82), and this risk increased to 2.66 (2.04–3.47) among individuals with diabetes for ≥15 years.
Asians with diabetes, like their Western counterparts, experience an increased risk of hip fracture. Early assessment for osteoporosis and increased fracture risk, as well as prevention of falls, should be part of the management of diabetes.
Epidemiologic studies associate lung cancer in non-smoking Chinese women with Chinese-style wok cooking. Our goal was to quantify carcinogen and toxicant biomarkers in Chinese women who reported regularly doing home cooking compared to women randomly selected from the Singapore Chinese Health Study as controls.
Biomarkers were quantified by high performance liquid chromatography-mass spectrometry (HPLC-MS), HPLC-with fluorescence detection, and gas chromatography-mass spectrometry.
Compared with controls, women who engaged in regular home cooking had significantly higher levels of mercapturic acids of acrolein [geometric mean 1959 pmol/mg creatinine (95% CI 1554–2467) vs.1370 (95% CI 1077–1742), P = 0.038], crotonaldehyde [geometric mean 232 pmol/mg creatinine (95% CI 193–277) vs. 142 (95% CI 118–171) P = 0.0004], and benzene [geometric mean 0.58 pmol/mg creatinine (95% CI 0.44–0.78) vs. 0.18 (95% CI 0.14–0.24) P < 0.0001]. No significant differences were found in levels of mercapturic acids of 1,3-butadiene, pyrene and phenanthrene metabolites, or acetaldehyde-leukocyte DNA adduct levels between the groups. Levels of the ethylene oxide mercapturic acid were significantly higher in the controls.
The higher levels of the mercapturic acid of benzene, a multi-organ carcinogen, in the women who cooked are particularly notable. Overall, the results showing increased exposure to the volatile toxicants and carcinogens acrolein, crotonaldehyde, and benzene in Chinese women who regularly cook provide a plausible lead for further investigating the role of volatile compounds generated during high temperature cooking with oils as causes of lung cancer.
A new direction for research on lung cancer etiology is suggested.
Carcinogen biomarkers; wok cooking; lung cancer
Soft drinks and other sweetened beverages may contribute to risk of type 2 diabetes and obesity. However, research has not addressed higher risk and Asian populations. The authors examined the association between soft drinks and juice and the risk of type 2 diabetes among Chinese Singaporeans enrolled in a prospective cohort study of 43,580 participants aged 45–74 years and free of diabetes and other chronic diseases at baseline. The incidence of physician-diagnosed type 2 diabetes was assessed by interview and validated; 2,273 participants developed diabetes during follow-up. After adjustment for potential lifestyle and dietary confounders, participants consuming ≥2 soft drinks per week had a relative risk of type 2 diabetes of 1.42 (95% confidence interval (CI): 1.25, 1.62) compared with those who rarely consumed soft drinks. Similarly, consumption of ≥2 juice beverages per week was associated with an increased risk (relative risk (RR) = 1.29, 95% CI: 1.05, 1.58). The association was modified by 5-year weight gain for ≥2 soft drinks per week among those who gained ≥3 kg (RR = 1.70, 95% CI: 1.34, 2.16) compared with those who gained less weight (RR = 1.20, 95% CI: 1.03, 1.41). Relatively frequent intake of soft drinks and juice is associated with an increased risk for development of type 2 diabetes in Chinese men and women.
Asian continental ancestry group; carbonated beverages; diabetes mellitus, type 2
We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×10−9; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.
The optimal range of relative weight for morbidity and mortality in Asian populations is an important question in need of more thorough investigation, especially as obesity rates increase. We aimed to examine the association between body mass index (BMI), all cause and cause-specific mortality to determine the optimal range of BMI in relation to mortality in Chinese men and women in Singapore.
We analyzed data from a prospective cohort study of 51,251 middle-aged or older (45–74) Chinese men and women in the Singapore Chinese Health Study. Participants were enrolled and data on body weight and covariates were collected in 1993–1998 and participants were followed through 2008. The analysis accounted for potential methodological issues through stratification on smoking and age, thorough adjustment of demographic and lifestyle confounders and exclusion of deaths early in the follow-up.
Increased risk of mortality was apparent in underweight (<18.5) and obese BMI categories (≥27.5) independent of age and smoking. Regardless of age or BMI, smoking considerably increased the rate of mortality and modified the association between BMI and mortality. The most favorable range of BMI for mortality rates and risk in non-smoking persons below age 65 was 18.5–21.4 kg/m2, and for non-smoking persons aged 65 and above was 21.5–24.4 kg/m2.