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Additional file 1. Additional meta-analysis.

BackgroundWhile the associations between individual lifestyle factors and risk of hepatocellular carcinoma (HCC) have been described previously, their combined impact on HCC risk is unknown.MethodsThe association of a composite score of healthy lifestyle factors, including body mass index, alcohol consumption, cigarette smoking, alternative Mediterranean diet, and sleep duration, and HCC risk was examined in the Singapore Chinese Health Study, an ongoing prospective cohort study of 63,257 Chinese men and women. Cox proportional hazard regression method was used to estimate HR and its 95% confidence interval (CI). Conditional logistic regression method was used to evaluate this composite lifestyle score-HCC risk association among a subset of individuals who tested negative for hepatitis B surface antigen (HBsAg) and anti-hepatitis C antibody.ResultsAfter a mean follow-up of 17.7 years, 561 participants developed HCC. Individuals with higher composite scores representing healthier lifestyles (range 0-8) were at significantly lower risk of HCC. Compared with the lowest composite score category (0-4), the HRs (95% CIs) for the composite scores of 5, 6, 7, and 8 were 0.67 (0.62-0.85), 0.61 (0.48-0.77), 0.49 (0.37-0.65), and 0.13 (0.06-0.30), respectively (P trend < 0.0001). A similar inverse association was observed in participants with negative HBsAg and anti-hepatitis C virus (HCV)-negative serology (HR, 0.38; 95% CI, 0.19-0.79; for the highest vs. the lowest category of the composite scores; P trend = 0.001).ConclusionsHealthy lifestyles protect against HCC development, especially for individuals without hepatitis B virus and HCV infections.ImpactThis study highlights the importance of a comprehensive lifestyle modification strategy for HCC primary prevention.

Circulating vitamin B6 levels have been found to be inversely associated with lung cancer. Most studies have focused on the B6 form pyridoxal 5′-phosphate (PLP), a direct biomarker influenced by inflammation and other factors. Using a functional B6 marker allows further investigation of the potential role of vitamin B6 status in the pathogenesis of lung cancer. We prospectively evaluated the association of the functional marker of vitamin B6 status, the 3-hydroxykynurenine:xanthurenic acid (HK:XA) ratio, with risk of lung cancer in a nested case–control study consisting of 5,364 matched case–control pairs from the Lung Cancer Cohort Consortium (LC3). We used conditional logistic regression to evaluate the association between HK:XA and lung cancer, and random effect models to combine results from different cohorts and regions. High levels of HK:XA, indicating impaired functional B6 status, were associated with an increased risk of lung cancer, the odds ratio comparing the fourth and the first quartiles (OR4th vs. 1st) was 1.25 (95% confidence interval, 1.10–1.41). Stratified analyses indicated that this association was primarily driven by cases diagnosed with squamous cell carcinoma. Notably, the risk associated with HK:XA was approximately 50% higher in groups with a high relative frequency of squamous cell carcinoma, i.e., men, former and current smokers. This risk of squamous cell carcinoma was present in both men and women regardless of smoking status.

Background: Secondhand smoke (SHS) exposure increases the risk of coronary heart disease (CHD) by an estimated 25-30% via oxidative stress and inflammatory mechanisms that may be ameliorated by die...

Objective: To evaluate the association between body mass index and mortality from overall cardiovascular disease and specific subtypes of cardiovascular disease in east and south Asians. Design: Pooled analyses of 20 prospective cohorts in Asia, including data from 835 082 east Asians and 289 815 south Asians. Cohorts were identified through a systematic search of the literature in early 2008, followed by a survey that was sent to each cohort to assess data availability. Setting: General populations in east Asia (China, Taiwan, Singapore, Japan, and Korea) and south Asia (India and Bangladesh). Participants: 1 124 897 men and women (mean age 53.4 years at baseline). Main outcome measures: Risk of death from overall cardiovascular disease, coronary heart disease, stroke, and (in east Asians only) stroke subtypes. Results: 49 184 cardiovascular deaths (40 791 in east Asians and 8393 in south Asians) were identified during a mean follow-up of 9.7 years. East Asians with a body mass index of 25 or above had a raised risk of death from overall cardiovascular disease, compared with the reference range of body mass index (values 22.5-24.9; hazard ratio 1.09 (95% confidence interval 1.03 to 1.15), 1.27 (1.20 to 1.35), 1.59 (1.43 to 1.76), 1.74 (1.47 to 2.06), and 1.97 (1.44 to 2.71) for body mass index ranges 25.0-27.4, 27.5-29.9, 30.0-32.4, 32.5-34.9, and 35.0-50.0, respectively). This association was similar for risk of death from coronary heart disease and ischaemic stroke; for haemorrhagic stroke, the risk of death was higher at body mass index values of 27.5 and above. Elevated risk of death from cardiovascular disease was also observed at lower categories of body mass index (hazard ratio 1.19 (95% confidence interval 1.02 to 1.39) and 2.16 (1.37 to 3.40) for body mass index ranges 15.0-17.4 and less than 15.0, respectively), compared with the reference range. In south Asians, the association between body mass index and mortality from cardiovascular disease was less pronounced than that in east Asians. South Asians had an increased risk of death observed for coronary heart disease only in individuals with a body mass index greater than 35 (hazard ratio 1.90, 95% confidence interval 1.15 to 3.12). Conclusions: Body mass index shows a U shaped association with death from overall cardiovascular disease among east Asians: increased risk of death from cardiovascular disease is observed at lower and higher ranges of body mass index. A high body mass index is a risk factor for mortality from overall cardiovascular disease and for specific diseases, including coronary heart disease, ischaemic stroke, and haemorrhagic stroke in east Asians. Higher body mass index is a weak risk factor for mortality from cardiovascular disease in south Asians.

Background: Tobacco smoking is a major risk factor for many diseases. We sought to quantify the burden of tobacco-smoking-related deaths in Asia, in parts of which men's smoking prevalence is among the world's highest. Methods and Findings: We performed pooled analyses of data from 1,049,929 participants in 21 cohorts in Asia to quantify the risks of total and cause-specific mortality associated with tobacco smoking using adjusted hazard ratios and their 95% confidence intervals. We then estimated smoking-related deaths among adults aged ≥45 y in 2004 in Bangladesh, India, mainland China, Japan, Republic of Korea, Singapore, and Taiwan—accounting for ∼71% of Asia's total population. An approximately 1.44-fold (95% CI = 1.37–1.51) and 1.48-fold (1.38–1.58) elevated risk of death from any cause was found in male and female ever-smokers, respectively. In 2004, active tobacco smoking accounted for approximately 15.8% (95% CI = 14.3%–17.2%) and 3.3% (2.6%–4.0%) of deaths, respectively, in men and women aged ≥45 y in the seven countries/regions combined, with a total number of estimated deaths of ∼1,575,500 (95% CI = 1,398,000–1,744,700). Among men, approximately 11.4%, 30.5%, and 19.8% of deaths due to cardiovascular diseases, cancer, and respiratory diseases, respectively, were attributable to tobacco smoking. Corresponding proportions for East Asian women were 3.7%, 4.6%, and 1.7%, respectively. The strongest association with tobacco smoking was found for lung cancer: a 3- to 4-fold elevated risk, accounting for 60.5% and 16.7% of lung cancer deaths, respectively, in Asian men and East Asian women aged ≥45 y. Conclusions: Tobacco smoking is associated with a substantially elevated risk of mortality, accounting for approximately 2 million deaths in adults aged ≥45 y throughout Asia in 2004. It is likely that smoking-related deaths in Asia will continue to rise over the next few decades if no effective smoking control programs are implemented.

Background: Although previous meta-analyses have suggested a dose-response relationship between body mass index (BMI) and thyroid cancer risk, limited evidence has been presented about Asian populations. To assess this association among Asian populations, where underweight is more prevalent than in other regions, a pooled analysis from the Asia Cohort Consortium was conducted.Methods: Baseline height and weight were measured in five cohorts and self-reported in eight cohorts. Thyroid cancer incidence was ascertained by linkage to local cancer registries. Cohorts were treated as a stratum in the Cox proportional hazard model to estimate the pooled hazard ratios (HRs) and corresponding confidence intervals (CIs) from the estimates for each cohort. All analyses were stratified by sex.Results: A total of 538,857 men and women from 13 cohorts from mainland China, Korea, Japan, and Singapore were included in the analysis. During a mean of 15.1 years of follow-up, 1132 thyroid cancer cases were ascertained. Using a BMI of 18.5-22.9 kg/m(2) as a reference, an elevated risk of thyroid cancer was observed for groups with a BMI between 25 and 29.9 kg/m(2) (HR: 1.31, [CI: 0.95-1.80]) and a BMI of 30 kg/m(2) and greater (HR: 1.84, [CI: 0.89-3.81]) in men. Thyroid cancer risk was elevated in women with a BMI of 23-24.9 kg/m(2) (HR: 1.26, [CI: 1.07-1.48]). The HRs for 5-U increment of BMI showed a linear association among men (HR: 1.25, [CI 1.10-1.55]) but not among women (HR: 1.07, [CI: 0.97-1.18]). Although the overall thyroid cancer risk was lower among underweight men and women, the papillary cancer risk may be elevated among underweight men (HR: 2.24, [CI: 0.75-6.66]).Conclusion: While higher BMI is associated with an elevated risk of thyroid cancer in both men and women, the association of underweight BMI may differ by sex and histological subtype.