Background

Evidence from basic research links exposure to endocrine disrupting chemicals (EDCs) with a higher risk for breast cancer. However, there is less evidence from observational epidemiological research and the results are equivocal. Therefore, we examined the association between occupational exposure to substances where exposure to EDCs is likely and the risk of breast cancer.

Methods

A prospective study consisting of a population-based cohort of 33,458 Singaporean Chinese women aged 45-74 years enrolled in the Singapore Chinese Health Study (SCHS) from 1993 to 98 and followed through 2014. Subjects' self-reported occupational exposure and duration to industries, job titles, and substance types were garnered at baseline, and cases of incident breast cancer (N = 988) were determined by linkage with the Singapore Cancer Registry. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated for exposure to substances, job titles, and industries.

Results

There was no association between cumulative exposure to substances via occupation where EDC exposure is likely and risk of breast cancer. These results were consistent for hypothesized high (HR 0.94, 95% CI: 0.66-1.35), medium (HR 1.03 95% CI: 0.77-1.38) and low (HR 0.74, 95% CI 0.48-1.13) combined substance exposure groups when compared with those who were not exposed via occupation. Similar null associations were observed when examining job titles and industry categories.

Conclusions

There was no association between EDC related occupational exposures and breast cancer risk in working women of the Singaporean Chinese Health Study. Future studies that employ rigorous methods with regard to exposure assessment of EDCs are needed.

Purpose

Prostate cancer (PCa) is the most commonly diagnosed cancer in men, resulting in a large cancer burden given a relatively higher 5-year survival rate of patients after cancer diagnosis. The underlying etiology of prostate cancer is not well understood. Chronic inflammation plays a significant role in carcinogenesis overall and may be involved in the development of PCa, but immune-related biomarker studies in prostate cancer are limited.

Methods

The associations of serum concentrations of cytokines, systemic immune biomarkers, with risk of PCa were assessed in a randomly selected sub-cohort (n = 798, mean age = 73 years) of the Osteoporotic Fractures in Men (MrOS) study, a prospective cohort of older men. At baseline, we measured serum interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor alpha (TNFα), soluble receptors (SR) of IL-6 (IL-6SR) and TNF (TNFαSR1 and TNFαSR2), and IL-10. The risk of PCa was calculated for higher tertile levels of measured individual cytokines relative to the lowest tertile using Cox proportional hazards regression models.

Results

After an average 6 years of follow-up, 59 men developed incident PCa. Men in the middle or highest tertile of IL-10 had a statistically significant 50% lower risk of PCa compared to the lowest tertile (hazard ratio = 0.50, 95% confidence interval = 0.30-0.84). There was no significant association between any of the other cytokines measured and PCa risk.

Conclusion

IL-10, an anti-inflammatory cytokine, was associated with lower risk of PCa. Further research of IL-10 and inflammation in relation to PCa development is warranted.

Background

Limited research has examined the association between dietary patterns and mortality, especially in non-Western populations.

Objective

We examined the association of dietary patterns with all-cause mortality and cause-specific mortality in the Singapore Chinese Health Study, which included a unique ethnic population with strong Western and South Asian cultural influences.

Design

We conducted a prospective data analysis of the Singapore Chinese Health Study, which included 52,584 Chinese men and women (aged 45-74 y) who were free of diabetes, cardiovascular disease (CVD), and cancer at baseline (1993-1998) and followed through 2011 with 10,029 deaths. The following 2 major dietary patterns were identified by using a principal components analysis: a vegetable-, fruit-, and soy-rich (VFS) pattern and a dim sum- and meat-rich (DSM) dietary pattern. Pattern scores for each participant were calculated and examined with all-cause and cause-specific mortality risks by using a Cox proportional hazards regression.

Results

The VFS pattern was inversely associated with all-cause mortality and each cause-specific category (CVD, cancer, and respiratory) of mortality during the follow-up period. Compared with the lowest quintile of the VFS pattern, HRs for quintiles 2-5 for all-cause mortality were 0.90, 0.79, 0.80, and 0.75, respectively (P-trend < 0.0001). The DSM pattern was positively associated with CVD mortality in the whole population (HR for fifth quintile compared with first quintile: 1.23; 95% CI: 1.07, 1.40; P-trend = 0.001). Positive associations between the DSM pattern and cancer and all-cause mortality were only present in ever-smokers. In ever-smokers, relative to the first quintile, HRs for quintiles 2-5 of the DSM pattern for all-cause mortality were 1.04, 1.04, 1.13, and 1.24, respectively (P-trend < 0.0001). Similarly, HRs for quintiles 2-5 for cancer mortality were 1.08, 1.03, 1.25, and 1.34, respectively (P-trend < 0.0001). The DSM pattern was not associated with respiratory mortality.

Conclusion

Dietary patterns are strongly associated with mortality in Chinese Singaporeans.

Background

There is limited research examining beverage habits, one of the most habitual dietary behaviors, with mortality risk.

Objective

This study examined the association between coffee, black and green tea, sugar-sweetened beverages (soft drinks and juice), and alcohol and all-cause and cause-specific mortality.

Methods

A prospective data analysis was conducted with the use of the Singapore Chinese Health Study, including 52,584 Chinese men and women (aged 45-74 y) free of diabetes, cardiovascular disease (CVD), and cancer at baseline (1993-1998) and followed through 2011 with 10,029 deaths. Beverages were examined with all-cause and cause-specific (cancer, CVD, and respiratory disease) mortality risk with the use of Cox proportional hazards regression.

Results

The associations between coffee, black tea, and alcohol intake and all-cause mortality were modified by smoking status. Among never-smokers there was an inverse dose-response association between higher amounts of coffee and black tea intake and all-cause, respiratory-related, and CVD mortality (black tea only). The fully adjusted HRs for all-cause mortality for coffee for <1/d, 1/d, and ≥2/d relative to no coffee intake were 0.89, 0.86, and 0.83, respectively (P-trend = 0.0003). For the same black tea categories the HRs were 0.95, 0.90, and 0.72, respectively (P-trend = 0.0005). Among ever-smokers there was no association between coffee or black tea and the outcomes. Relative to no alcohol, light to moderate intake was inversely associated with all-cause mortality (HR: 0.87; 95% CI: 0.79, 0.96) in never-smokers with a similar magnitude of association in ever-smokers. There was no association between heavy alcohol intake and all-cause mortality in never-smokers and a strong positive association in ever-smokers (HR: 1.56; 95% CI: 1.40, 1.74). Green tea and sugar-sweetened beverages were not associated with all-cause or cause-specific mortality.

Conclusions

Higher coffee and black tea intake was inversely associated with mortality in never-smokers, light to moderate alcohol intake was inversely associated with mortality regardless of smoking status, heavy alcohol intake was positively associated with mortality in ever-smokers, and there was no association between sugar-sweetened beverages and green tea and mortality.

Background

The American Diabetes Association recently included glycated hemoglobin in the diagnostic criteria for diabetes, but research on the utility of this biomarker in Southeast Asians is scant. The aim of this study was to evaluate the association between percent HbA1c and incident diabetes in an Asian population of adult men and women without reported diabetes.

Methods

Data analysis of 5,770 men and women enrolled in the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999-2004) and had no cancer and no reported history of diabetes or cardiovascular disease events. Diabetes was defined as self-report of physician diagnosis, identified at the follow-up II visit (2006-2010).

Results

Hazard ratios (and 95% confidence intervals) for incident diabetes by 5 categories of HbA1c were estimated with Cox regression models and continuous HbA1c with cubic spline analysis. Compared to individuals with an HbA1c ≤ 5.7% (≤39 mmol/mol), individuals with HbA1c 5.8-5.9% (40-41 mmol/mol), 6.0-6.1% (42-43 mmol/mol), 6.2-6.4% (44-47 mmol/mol), and ≥ 6.5% (≥48 mmol/mol) had significantly increased risk for incident diabetes during follow-up. In cubic spline analysis, levels below 5.7% HbA1c were not significantly associated with incident diabetes.

Conclusions

Our study found a strong and graded association with HbA1c 5.8% and above with incident diabetes in Chinese men and women.

Objective

Glycated hemoglobin (HbA₁c) is a robust biomarker of the preceding 2 to 3 months average blood glucose level. The aim of this study was to examine the association between HbA₁c and mortality in a cohort of Southeast Asians.

Research design and methods

Analysis of 7,388 men and women, mean age 62 years, from the Singapore Chinese Health Study who provided a blood sample at the follow-up I visit (1999-2004) and reported no history of diabetes, previous adverse cardiovascular events, or cancer. A total of 888 deaths were identified through 31 December 2011 via registry linkage. Participants represented a random study sample of potential control subjects for a nested case-control genome-wide association study of type 2 diabetes in the population. Hazard ratios (HRs) for all-cause and cause-specific mortality by six categories of HbA1c were estimated with Cox regression models.

Results

Relative to participants with an HbA₁c of 5.4-5.6% (36-38 mmol/mol), participants with HbA₁c ≥6.5% (≥48 mmol/mol) had an increased risk of all-cause, cardiovascular, and cancer mortality during an average of 10.1 years of follow-up; HRs (95% CIs) were 1.96 (1.56-2.46), 2.63 (1.77-3.90), and 1.51 (1.04-2.18), respectively. No level of HbA1c was associated with increased risk of respiratory mortality. Levels <6.5% HbA₁c were not associated with mortality during follow-up. The results did not materially change after excluding observation of first 3 years post-blood draw.

Conclusions

HbA₁c levels consistent with undiagnosed type 2 diabetes (≥6.5%) are associated with an increased risk of all-cause and cause-specific mortality in Chinese men and women.

Few studies have examined the association between body mass index (BMI: kg/m(2)) and pancreatic cancer risk in Asian populations. We examined this relationship in 51,251 Chinese men and women aged 45-74 who enrolled between 1993 and 1998 in the population based, prospective Singapore Chinese Health Study. Data were collected through in-person interviews. By December 31, 2011, 194 cohort participants had developed pancreatic cancer. A Cox proportional hazards model was used to estimate hazard ratios (HR) and their 95% confidence intervals (95% CI). We hypothesized the association between BMI and pancreatic cancer risk may vary by smoking status (ever v. never) and there was evidence for this as the interaction between BMI and smoking status was significant (p = 0.018). Among ever smokers, being classified as underweight (BMI <18.5 kg/m(2)), was associated with a significantly elevated risk of pancreatic cancer relative to smokers with a BMI of 21.5-24.4 kg/m(2) (HR = 1.99, 95% CI  =  1.03-3.84). This association was strengthened after exclusion of the first three years of follow-up time. Among never smokers, there was no association between BMI and pancreatic cancer risk. However, after excluding pancreatic cancer cases and person-years in the first three years of follow-up, never smokers with a BMI ≥ 27.5 kg/m(2) showed a suggestive increased risk of pancreatic cancer relative to never smokers with a BMI of 21.5-24.4 kg/m(2) (HR  =  1.75, 95% CI  =  0.93-3.3). In conclusion, Singaporean Chinese who were underweight with a history of smoking had an increased risk of developing pancreatic cancer, whereas there was no significant association between BMI and pancreatic cancer in never smokers.

Background

Although studies suggest that omega-3 fatty acids intake may reduce cardiovascular disease (CVD) mortality risk, few studies have differentiated dietary eicosapentaenoic/docosahexaenoic acid (EPA/DHA) from alpha-linolenic acid (ALA), and epidemiological research in Asian populations is limited.

Methods

The Singapore Chinese Health Study is a population-based cohort that recruited 63,257 Chinese adults aged 45-74 years from 1993 to 1998. Usual diet was measured at recruitment using a validated semiquantitative food-frequency questionnaire, and mortality information was identified via registry linkage up to 31 December 2011. Cox proportional hazard models were used to calculate hazard ratios (HRs) with adjustment for potential confounders.

Results

We documented 4780 cardiovascular deaths (including 2697 coronary heart disease (CHD) deaths and 1298 stroke deaths) during 890,473 person-years of follow up. Omega-3 fatty acids intake was monotonically associated with reduced risk of cardiovascular mortality. Compared to the lowest quartile, the HR was 0.88 (95% confidence interval, CI, 0.81-0.96), 0.88 (95% CI 0.80-0.97), and 0.83 (95% CI 0.74-0.92) for the second, third, and highest quartile, respectively (p-trend = 0.003). Both EPA/DHA and ALA were independently associated with reduced risk of cardiovascular mortality: HR comparing extreme quartiles was 0.86 (95% CI 0.77-0.96, p-trend = 0.002) and 0.81 (95% CI 0.73-0.90, p-trend < 0.001), respectively. The associations were similar for deaths from CHD and stroke and persisted in participants who were free of CVD at baseline.

Conclusions

Higher intakes of marine (EPA/DHA) and plant (ALA) omega-3 fatty acids are both associated with reduced risk of cardiovascular mortality in a Chinese population.

We aimed to examine the prospective association between plasma FAs, oxylipins, and risk of acute myocardial infarction (AMI) in a Singapore Chinese population. A nested case-control study with 744 incident AMI cases and 744 matched controls aged 47-83 years was conducted within the Singapore Chinese Health Study. Nineteen plasma FAs and 12 oxylipins were quantified using MS. These were grouped into 12 FA clusters and 5 oxylipin clusters using hierarchical clustering, and their associations with AMI risk were assessed. Long-chain n-3 FAs [odds ratio (OR) = 0.67 per SD increase, 95% confidence interval (CI): 0.53-0.84, P < 0.001] and stearic acid (OR = 0.65, 95% CI: 0.44-0.97, P = 0.03) were inversely associated with AMI risk, whereas arachidonic acid (AA) was positively associated with AMI risk (OR = 1.25, 95% CI: 1.03-1.52, P = 0.02) in the multivariable model with adjustment for other FAs. Further adjustment for oxylipins did not substantially change these associations. An inverse association was observed between AA-derived oxylipin, thromboxane (TX)B2, and AMI risk (OR = 0.81, 95% CI: 0.71-0.93, P = 0.003). Circulating long-chain n-3 FAs and stearic acid were associated with a lower and AA was associated with a higher AMI risk in this Chinese population. The association between the oxylipin TXB2 and AMI requires further research.

EGFR polymorphisms have not been thoroughly evaluated for association with head and neck squamous cell carcinoma (HNSCC) risk. We genotyped 578 HNSCC patients and 588 cancer-free controls for 60 EGFR single nucleotide polymorphisms (SNPs) and tested associations with HNSCC risk. EGFR intronic SNPs rs12535536, rs2075110, rs1253871, rs845561 and rs6970262 and synonymous SNP rs2072454 were associated with HNSCC risk among all subjects (p < 0.05). SNPs rs12538371, rs845561, and rs6970262 were significantly associated with HNSCC risk (p < 0.05) among never tobacco users. We identified EGFR variants that likely modify risk for HNSCC including three variants that contribute to tobacco-independent risk.