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Abstract Background Residential mobility is believed to influence the occurrence and development of cancer; however, the results are inconclusive. Furthermore, limited studies have been conducted on Asian populations. This study aimed to evaluate the relationship between residential mobility and liver cancer risk among Chinese women. Methods We enrolled 72,818 women from urban Shanghai between 1996 and 2000, and then followed them until the end of 2016. Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the association between residential mobility and liver cancer risk. A linear trend test was conducted by ranking variables. A sensitivity analysis was also conducted, excluding participants with follow-up times of less than 2 years, to prevent potential bias. Results During the 1,269,765 person-years of follow-up, liver cancer was newly diagnosed in 259 patients. Domestic migration (HR = 1.47, 95% CI, 1.44–1.50), especially immigration to Shanghai (HR = 1.47, 95% CI, 1.44–1.50) was associated with an increased risk of liver cancer. In addition, migration frequency, age at initial migration and first immigration to Shanghai had linear trends with an increased liver cancer risk (P trend

Abstract Background Using the published survival statistics from cancer registration or population‐based studies, we aimed to describe the global pattern and trend of lung cancer survival. Methods By searching SinoMed, PubMed, Web of Science, EMBASE, and SEER, all survival analyses from cancer registration or population‐based studies of lung cancer were collected by the end of November 2022. The survival rates were extracted by sex, period, and country. The observed, relative, and net survival rates of lung cancer were applied to describe the pattern and time changes from the late 1990s to the early 21st century. Results Age‐standardized 5‐year relative/net survival rate of lung cancer was typically low, with 10%–20% for most regions. The highest age‐standardized relative/net survival rate was observed in Japan (32.9%, 2010–2014), and the lowest was in India (3.7%, 2010–2014). In most countries, the five‐year age‐standardized relative/net survival rates of lung cancer were higher in females and younger people. The patients with adenocarcinoma had a better prognosis than other groups. In China, the highest 5‐year overall relative/net survival rates were 27.90% and 31.62% in men and women in Jiangyin (2012–2013). Conclusion Over the past decades, the prognosis of lung cancer has gradually improved, but significant variations were also observed globally. Worldwide, a better prognosis of lung cancer can be observed in females and younger patients. It is essential to compare and evaluate the histological or stage‐specific survival rates of lung cancer between different regions in the future.

Summary: Background: Previous metabolic profiling of liver cancer has mostly used untargeted metabolomic approaches and was unable to quantitate the absolute concentrations of metabolites. In this study, we examined the association between the concentrations of 186 targeted metabolites and liver cancer risk using prediagnostic plasma samples collected up to 14 years prior to the clinical diagnosis of liver cancer. Methods: We conducted a nested case–control study (n = 322 liver cancer cases, n = 322 matched controls) within the Shanghai Men's Health Study. Conditional logistic regression models adjusted for demographics, lifestyle factors, dietary habits, and related medical histories were used to estimate the odds ratios. Restricted cubic spline functions were used to characterise the dose–response relationships between metabolite concentrations and liver cancer risk. Findings: After adjusting for potential confounders and correcting for multiple testing, 28 metabolites were associated with liver cancer risk. Significant non-linear relationships were observed for 22 metabolites. The primary bile acid biosynthesis and phenylalanine, tyrosine and tryptophan biosynthesis were found to be important pathways involved in the aetiology of liver cancer. A metabolic score consisting of 10 metabolites significantly improved the predictive ability of traditional epidemiological risk factors for liver cancer, with an optimism-corrected AUC increased from 0.84 (95% CI: 0.81–0.87) to 0.89 (95% CI: 0.86–0.91). Interpretation: This study characterised the dose–response relationships between metabolites and liver cancer risk, providing insights into the complex metabolic perturbations prior to the clinical diagnosis of liver cancer. The metabolic score may serve as a candidate risk predictor for liver cancer. Funding: National Key Project of Research and Development Program of China [2021YFC2500404, 2021YFC2500405]; US National Institutes of Health [subcontract of UM1 CA173640].

Background: The objective was to evaluate the effects of personal characteristics on the validation of self-reported type 2 diabetes among Chinese adults in urban Shanghai. Methods: During 2015 through 2016, 4,322 participants were recruited in this validation study. We considered the criteria of diabetes verification to use the laboratory assays of fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), or self-reported use of diabetic medication. Results: When taking diabetic medication or FPG ≥7.0 mmol/L was as identified diabetes, the measurements of sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Kappa value of self-reported diabetes were 72.0%, 99.2%, 95.1%, 93.9%, and 0.78, respectively. If an additional HbA1c test was used for 708 subjects (aged

In breast cancer, genome-wide associations studies (GWAS) have highlighted loci associated with disease risk. Here, the authors perform a meta-analysis of GWAS data from Asian populations, discovering 31 potential new risk loci, 10 of which are validated in an independent disease cohort.

Abstract Background Epidemiological studies on the association between coffee intake and cancer risk have yielded inconsistent results. To summarize and appraise the quality of the current evidence, we conducted an umbrella review of existing findings from meta-analyses of observational studies. Methods We searched PubMed, Embase, Web of Science and the Cochrane database to obtain systematic reviews and meta-analyses of associations between coffee intake and cancer incidence. For each association, we estimated the summary effect size using the fixed- and random-effects model, the 95% confidence interval, and the 95% prediction interval. We also assessed heterogeneity, evidence of small-study effects, and excess significance bias. Results Twenty-eight individual meta-analyses including 36 summary associations for 26 cancer sites were retrieved for this umbrella review. A total of 17 meta-analyses were significant at P ≤ 0.05 in the random-effects model. For the highest versus lowest categories, 4 of 26 associations had a more stringent P value (P ≤ 10− 6). Associations for five cancers were significant in dose-response analyses. Most studies (69%) showed low heterogeneity (I2 ≤ 50%). Three and six associations had evidence of excessive significance bias and publication bias, respectively. Coffee intake was inversely related to the risk of liver cancer and endometrial cancer and was characterized by dose-response relationships. There were no substantial changes when we restricted analyses to meta-analysis of cohort studies. Conclusions There is highly suggestive evidence for an inverse association between coffee intake and risk of liver and endometrial cancer. Further research is needed to provide more robust evidence for cancer at other sites.

Sleep duration is associated with an adverse lipid profile. Here, the authors perform genome-wide gene-by-sleep interaction analysis and find 49 previously unreported lipid loci when considering short or long total sleep time.

Background: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets. Methods: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets. Findings: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P

GWAS have identified more than 500 genetic loci associated with blood lipid levels. Here, the authors report a genome-wide analysis of interactions between genetic markers and physical activity, and find that physical activity modifies the effects of four genetic loci on HDL or LDL cholesterol.

Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.

We previously identified 10 lung adenocarcinoma susceptibility loci in a genome-wide association study (GWAS) conducted in the Female Lung Cancer Consortium in Asia (FLCCA), the largest genomic study of lung cancer among never-smoking women to date. Furthermore, household coal use for cooking and heating has been linked to lung cancer in Asia, especially in Xuanwei, China. We investigated the potential interaction between genetic susceptibility and coal use in FLCCA. We analyzed GWAS-data from Taiwan, Shanghai, and Shenyang (1472 cases; 1497 controls), as well as a separate study conducted in Xuanwei (152 cases; 522 controls) for additional analyses. We summarized genetic susceptibility using a polygenic risk score (PRS), which was the weighted sum of the risk-alleles from the 10 previously identified loci. We estimated associations between a PRS, coal use (ever/never), and lung adenocarcinoma with multivariable logistic regression models, and evaluated potential gene-environment interactions using likelihood ratio tests. There was a strong association between continuous PRS and lung adenocarcinoma among never coal users (Odds Ratio (OR) = 1.69 (95% Confidence Interval (CI) = 1.53, 1.87), p=1 × 10−26). This effect was attenuated among ever coal users (OR = 1.24 (95% CI: 1.03, 1.50), p = 0.02, p-interaction = 6 × 10−3). We observed similar attenuation among coal users from Xuanwei. Our study provides evidence that genetic susceptibility to lung adenocarcinoma among never-smoking Asian women is weaker among coal users. These results suggest that lung cancer pathogenesis may differ, at least partially, depending on exposure to coal combustion products. Notably, these novel findings are among the few instances of sub-multiplicative gene-environment interactions in the cancer literature.

Endometrial cancer is the most common invasive gynaecological cancer in developed countries. Here a meta-analysis identifies an additional nine novel endometrial cancer risk loci and eQTL analysis reveals risk variants associate with reduced expression of negative regulators of oncogenic signal transduction proteins.

Abstract Impact of combined lifestyles on risk of mortality needs to be explored quantitatively. We aimed to evaluate the associations of combined lifestyle factors with total and cause-specific mortality in Chinese men. We used data from the Shanghai Men’s Health Study (2002–2013), an on-going population-based prospective cohort study of men (aged 40 to 74 years). Four traditional unfavorable lifestyle factors were included: smoking, heavy alcohol use, unhealthy diet and physical inactivity. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). Among about 61,480 men in the cohort, a total of 4,952 men died, of which 1,637 men died from cardiovascular diseases (CVD), 2,122 from cancer during a median of 9.29 years’ follow-up. The HRs of men with four risk practices comparing to those with zero were 2.92 (95%CI: 2.53, 3.38) for all-cause mortality, 3.15 (95%CI: 2.44, 4.05) for CVD mortality, and 3.18 (95%CI: 2.55, 3.97) for cancer mortality. The population attributable risks (PARs) were 0.41, 0.40 and 0.38 for total, CVD and cancer mortality, accordingly. As combined unhealthy lifestyle behaviors had substantial impact on total and cause-specific mortality, promotion of healthy lifestyle should be a public health priority.

ObjectiveTo study the association of educational level and risk of death from all causes, cardiovascular disease (CVD) and cancer among Asian populations.DesignA pooled analysis of 15 population-based cohort studies.Setting and participants694 434 Asian individuals from 15 prospective cohorts within the Asia Cohort Consortium.InterventionsNone.Main outcome measuresHRs and 95% CIs for all-cause mortality, as well as for CVD-specific mortality and cancer-specific mortality.ResultsA total of 694 434 participants (mean age at baseline=53.2 years) were included in the analysis. During a mean follow-up period of 12.5 years, 103 023 deaths were observed, among which 33 939 were due to cancer and 34 645 were due to CVD. Higher educational levels were significantly associated with lower risk of death from all causes compared with a low educational level (≤primary education); HRs and 95% CIs for secondary education, trade/technical education and ≥university education were 0.88 (0.85 to 0.92), 0.81 (0.73 to 0.90) and 0.71 (0.63 to 0.80), respectively (ptrend=0.002). Similarly, HRs (95% CIs) were 0.93 (0.89 to 0.97), 0.86 (0.78 to 0.94) and 0.81 (0.73 to 0.89) for cancer death, and 0.88 (0.83 to 0.93), 0.77 (0.66 to 0.91) and 0.67 (0.58 to 0.77) for CVD death with increasing levels of education (both ptrend

Background Trimethylamine‐N‐oxide (TMAO), a diet‐derived, gut microbial–host cometabolite, has been associated with adverse cardiovascular outcomes in patient populations; however, evidence is lacking from prospective studies conducted in general populations and non‐Western populations. Methods and Results We evaluated urinary levels of TMAO and its precursor metabolites (ie, choline, betaine, and carnitine) in relation to risk of coronary heart disease (CHD) among Chinese adults in a nested case–control study, including 275 participants with incident CHD and 275 individually matched controls. We found that urinary TMAO, but not its precursors, was associated with risk of CHD. The odds ratio for the highest versus lowest quartiles of TMAO was 1.91 (95% CI, 1.08–3.35; Ptrend=0.008) after adjusting for CHD risk factors including obesity, diet, lifestyle, and metabolic diseases and 1.75 (95% CI, 0.96–3.18; Ptrend=0.03) after further adjusting for potential confounders or mediators including central obesity, dyslipidemia, inflammation, and intake of seafood and deep‐fried meat or fish, which were associated with TMAO level in this study. The odds ratio per standard deviation increase in log‐TMAO was 1.30 (95% CI, 1.03–1.63) in the fully adjusted model. A history of diabetes mellitus modified the TMAO–CHD association. A high TMAO level (greater than or equal to versus lower than the median) was associated with odds ratios of 6.21 (95% CI, 1.64–23.6) and 1.56 (95% CI, 1.00–2.43), respectively, among diabetic and nondiabetic participants (Pinteraction=0.02). Diabetes mellitus status also modified the associations of choline, betaine, and carnitine with risk of CHD; significant positive associations were found among diabetic participants, but null associations were noted among total and nondiabetic participants. Conclusions Our study suggests that TMAO may accelerate the development of CHD, highlighting the importance of diet–gut microbiota–host interplay in cardiometabolic health.

Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.

Epidemiological studies have reported inconsistent association between obesity and risk of bladder cancer, and the dose-response relationship between them has not been clearly defined.We carried out a meta-analysis to summarize available evidence from epidemiological studies on this point. Relevant articles were identified by searching the PubMed and Web of Science databases through September 30, 2014. We pooled the relative risks from individual studies using random-effect model, and the dose-response relationship was estimated by using restricted cubic spline model.Fifteen cohort studies with 38,072 bladder cancer cases among 14,201,500 participants were included. Compared to normal weight, the pooled relative risks and corresponding 95% confidence intervals of bladder cancer were 1.07(1.01-1.14) and 1.10(1.06-1.14) for preobese and obesity, with moderate (I² = 37.6%, P = 0.029) and low (I² = 15.5%, P = 0.241) heterogeneities between studies, respectively. In a dose-response meta-analysis, body mass index (BMI) was associated with bladder cancer risk in a linear fashion (P(non-linearity) = 0.467) and the risk increased by 4.2% for each 5 kg/m2 increase. No significant publication bias was found (P = 0.912 for Begg's test, P = 0.712 for Egger's test).Findings from this dose-response meta-analysis suggest obesity is associated with linear-increased risk of bladder cancer.

Asians have high prevalence of central obesity despite the low prevalence of general obesity. We evaluated associations between the central obesity measure, waist-hip ratio (WHR) with total and cause-specific mortality in middle-aged and elderly Chinese participants. Data arise from two prospective population-based cohort studies: the Shanghai Men's Health Study involves 53,425 men (participation rate = 74.0%), age 40-74 at baseline, and the Shanghai Women's Health Study involves 63,017 women (participation rate = 92.7%), age 40-70 at baseline. Information on lifestyle factors and anthropometric measurements were taken at baseline interview. Vital status and causes of death were obtained via surveys and annual linkages to relevant Shanghai registries through December 31, 2011. After median follow-up time of 7.5 years for the Shanghai Men's Health Study and 13.2 years for the Shanghai Women's Health Study, there were 2,058 and 3,167 deaths, respectively. In models adjusted for BMI and other potential confounders, WHR was associated with all-cause mortality; hazard ratios (HRs) (95% confidence intervals) across the first to fifth quintile increased from 1 (Reference), 1.10 (0.95,1.27), 1.21 (1.04,1.41), 1.11 (0.96,1.30), to 1.42 (1.22,1.65) in men and from 1 (Reference), 1.10 (0.96,1.27), 1.11 (0.97,1.27), 1.20 (1.05,1.37), to 1.48 (1.30,1.69) in women. WHR had a stronger association with cardiovascular disease, with multivariate-adjusted HRs of 1.5 to 1.7 observed for the highest versus lowest quintile of WHR. Dose-response associations were also seen for cancer and other-cause deaths. Stratified analyses suggested a stronger association with mortality among normal weight (BMI

BackgroundTobacco 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 findingsWe 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.ConclusionsTobacco 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. Please see later in the article for the Editors' Summary.

To evaluate associations of premature ovarian failure (POF) with mortality and morbidity in Asian populations.We identified 1,003 cases of POF among 36,402 postmenopausal women who participated in the Shanghai Women's Health Study, a population-based cohort study. Cox regression and logistic regression models were applied in data analysis.After adjustment for potential confounding factors, we found that POF increased the risk of total and cancer-specific mortality (HR (95%CIs): 1.29 (1.08-1.54) and 1.38 (1.05-1.81), respectively). POF was also associated with high prevalence of autoimmune disease (OR (95%CI): 1.56 (1.04-2.35)) but decreased incidence of breast cancer (OR (95%CI): 0.59 (0.38-0.91)). Similar results were observed when hormone replacement therapy users were excluded from the analysis. POF is associated with high waist-to-hip ratio.Our results suggest that women with POF experience increased mortality and that these women may benefit from heightened surveillance and appropriate interventions.

Most previous studies of meat intake and total or cause-specific mortality were conducted in North America, whereas studies in other areas have been limited and reported inconsistent results. This study investigated the association of red meat or poultry intake with risk of total and cause-specific mortality, including cancer and cardiovascular disease (CVD), in two large population-based prospective cohort studies of 134,290 Chinese adult women and men in Shanghai. Meat intakes were assessed through validated food frequency questionnaires administered in person at baseline. Vital status and dates and causes of deaths were ascertained through annual linkage to the Shanghai Vital Statistics Registry and Shanghai Cancer Registry databases and home visits every 2-3 years. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of death associated with quintiles of meat intake. During 803,265 person-years of follow up for women and 334,281 person-years of follow up for men, a total of 4,210 deaths in women and 2,733 deaths in men accrued. The median intakes of red meat were 43 g/day among women and 54 g/day among men, and pork constituted at least 95% of total meat intake for both women and men. Red meat intake was associated with increased total mortality among men, but not among women; the HR (95% CI) comparing the highest with the lowest quintiles were 1.18 (1.02-1.35) and 0.92 (0.82-1.03), respectively. This sex difference was statistically significant (P = 0.01). Red meat intake was associated with increased risk of ischemic heart disease mortality (HR = 1.41, 95% CI = 1.05-1.89) and with decreased risk of hemorrhagic stroke mortality (HR = 0.62, 95% CI = 0.45-0.87). There were suggestive inverse associations of poultry intake with risk of total and all-CVD mortality among men, but not among women. Further investigations are needed to elucidate the sex-specific associations between red meat intake and mortality.

OBJECTIVES: We examined the incidence trends of bladder and kidney cancers using a population-based cancer registration data. METHODS: Age-standardized incidence rates were analyzed using data from the Shanghai Cancer Registry during 1973 to 2005. Annual percentage changes and 95% confidence intervals were calculated to evaluate the incidence changes. Age-period-cohort analysis was further implemented to assess the contributions of age, period and cohort effects to the trends using the intrinsic estimator method. RESULTS: In total, 12,676 bladder and 5,811 kidney cancer patients were registered in urban Shanghai. The age-standardized rates of bladder cancer in males increased from 6.39 to 7.66 per 100,000, or 0.62% per year, whereas the rates in females increased from 1.95 to 2.09 per 100,000, or 0.33% per year. For kidney cancer, the age-standardized rates in males increased from 1.20 to 5.64 per 100,000, or 6.98% per year. Similarly in females, the rates increased from 0.85 to 3.33 per 100,000, or 5.93% per year. Age-period-cohort analysis showed increasing curves of age and period effects but generally decreasing cohort effects for bladder and kidney cancers. CONCLUSIONS: Our results show increasing incidence trends of bladder and kidney cancers in Chinese men and women, especially for kidney cancer.

In vitro studies have demonstrated the role of the BCL-2 family of genes in endometrial carcinogenesis. The role of genetic variants in BCL-2 genes and their interactions with non-genetic factors in the development of endometrial cancer has not been investigated in epidemiological studies.We examined the relationship between BCL-2 gene family variants and endometrial cancer risk among 1,028 patients and 1,922 age-matched community controls from Shanghai, China. We also investigated possible interactions between genetic variants and established risk factors (demographic, lifestyle and clinical). Individuals were genotyped for 86 tagging single nucleotide polymorphisms (SNPs) in the BCL2, BAX, BAD and BAK1 genes.Significant associations with endometrial cancer risk were found for 9 SNPs in the BCL2 gene (P trend

Age at natural menopause (ANM) is a complex trait with high heritability and is associated with several major hormonal-related diseases. Recently, several genome-wide association studies (GWAS), conducted exclusively among women of European ancestry, have discovered dozens of genetic loci influencing ANM. No study has been conducted to evaluate whether these findings can be generalized to Chinese women.We evaluated the index single nucleotide polymorphisms (SNPs) in 19 GWAS-identified genetic susceptibility loci for ANM among 3,533 Chinese women who had natural menopause. We also investigated 3 additional SNPs which were in LD with the index SNP in European-ancestry but not in Asian-ancestry populations. Two genetic risk scores (GRS) were calculated to summarize SNPs across multiple loci one for all SNPs tested (GRSall), and one for SNPs which showed association in our study (GRSsel). All 22 SNPs showed the same association direction as previously reported. Eight SNPs were nominally statistically significant with P≤0.05: rs4246511 (RHBDL2), rs12461110 (NLRP11), rs2307449 (POLG), rs12611091 (BRSK1), rs1172822 (BRSK1), rs365132 (UIMC1), rs2720044 (ASH2L), and rs7246479 (TMEM150B). Especially, SNPs rs4246511, rs365132, rs1172822, and rs7246479 remained significant even after Bonferroni correction. Significant associations were observed for GRS. Women in the highest quartile began menopause 0.7 years (P = 3.24×10(-9)) and 0.9 years (P = 4.61×10(-11)) later than those in the lowest quartile for GRSsel and GRSall, respectively.Among the 22 investigated SNPs, eight showed associations with ANM (P

Type 2 diabetes mellitus (T2DM) is a prevalent chronic disease worldwide. The prevalence of T2DM is increasing rapidly in China. Understanding the contribution of modifiable lifestyle factors on T2DM risk is imperative to prevent the development of T2DM in China.We examined associations between lifestyle factors including physical activity, smoking and alcohol consumption with incidence of T2DM among middle-aged and elderly men in urban Shanghai. Information on socio-demographics, lifestyle habits, dietary habits, and disease history was collected via in-person interviews. Anthropometric measurements were taken. A total of 51 464 Chinese men aged 40-74 years free of T2DM, coronary heart disease (CHD), and stroke at baseline were included in the current study. Incident T2DM was identified through follow-up surveys conducted every 2-3 years. Cox proportional hazard analyses were conducted to evaluate associations between lifestyle risk factors and incidence of T2DM.We documented 1304 new cases of T2DM during 276 929 person-years of follow-up (average: 5.4 years). Physical activity was inversely associated with T2DM risk. Daily living, commuting, and total physical activity METs had inverse negative dose-response relationships with T2DM (P-trend = 0.0033, 0.0022, and

Genetic factors play an important role in the etiology of both sporadic and familial breast cancer. We aimed to discover novel genetic susceptibility loci for breast cancer. We conducted a four-stage genome-wide association study (GWAS) in 19,091 cases and 20,606 controls of East-Asian descent including Chinese, Korean, and Japanese women. After analyzing 690,947 SNPs in 2,918 cases and 2,324 controls, we evaluated 5,365 SNPs for replication in 3,972 cases and 3,852 controls. Ninety-four SNPs were further evaluated in 5,203 cases and 5,138 controls, and finally the top 22 SNPs were investigated in up to 17,423 additional subjects (7,489 cases and 9,934 controls). SNP rs9485372, near the TGF-β activated kinase (TAB2) gene in chromosome 6q25.1, showed a consistent association with breast cancer risk across all four stages, with a P-value of 3.8×10(-12) in the combined analysis of all samples. Adjusted odds ratios (95% confidence intervals) were 0.89 (0.85-0.94) and 0.80 (0.75-0.86) for the A/G and A/A genotypes, respectively, compared with the genotype G/G. SNP rs9383951 (P = 1.9×10(-6) from the combined analysis of all samples), located in intron 5 of the ESR1 gene, and SNP rs7107217 (P = 4.6×10(-7)), located at 11q24.3, also showed a consistent association in each of the four stages. This study provides strong evidence for a novel breast cancer susceptibility locus represented by rs9485372, near the TAB2 gene (6q25.1), and identifies two possible susceptibility loci located in the ESR1 gene and 11q24.3, respectively.

More than 40 genetic susceptibility loci have been reported for type 2 diabetes (T2D). Recently, the combined effect of genetic variants has been investigated by calculating a genetic risk score. We evaluated 36 genome-wide association study (GWAS) identified SNPs in 2,679 T2D cases and 3322 controls in middle-age Han Chinese. Fourteen SNPs were significantly associated with T2D in analysis adjusted for age, sex and BMI. We calculated two genetic risk scores (GRS) (GRS1 with all the 36 SNPs and GRS2 with the 14 SNPs significantly associated with T2D). The odds ratio for T2D with each GRS point (per risk allele) was 1.08 (95% CI: 1.06-1.09) for GRS1 and 1.15 (95% CI: 1.13-1.18) for GRS2. The OR for quintiles were 1.00, 1.26, 1.69, 1.95 and 2.18 (P

Lack of cancer incidence information for adolescents and young adults led us to describe incidence trends within the young population of 15 to 49 year-olds in urban Shanghai between 1973 and 2005.During 1973 to 2005, data on 43,009 (45.8%) male and 50,828 (54.2%) female cancer cases aged 15-49 years from the Shanghai Cancer Registry were analyzed. Five-year age-specific rates, world age-standardized rates, percent change (PC), and annual percent change (APC) were calculated using annual data on population size and its estimated age structure.During the 33-year study period, overall cancer incidence of adolescents and young adults among males marginally decreased by 0.5% per year (P

To evaluate the associations of age at menarche and the leg length-to-sitting-height ratio, markers of adolescent growth, with risk of diabetes in later life.Information from 69,385 women and 55,311 men, aged 40-74 years from the Shanghai Women's Health Study and Shanghai Men's Health Study, were included in the current analyses. Diabetes status was ascertained through biennial in person follow-up. Cox models, with age as the time scale, were used.There were 2369 cases of diabetes (1831 women; 538 men) during an average of 7.3 and 3.6 years of follow-up of the women and men, respectively. In females, menarche age was inversely associated with diabetes risk after adjustment for birth cohort, education, and income (HR = 0.95, 0.92-0.98). In both genders, leg length-to-sitting-height ratio was inversely related to diabetes (HR = 0.88, 0.80-0.97 for men; HR = 0.91, 0.86-0.96 for women) after adjustment for birth cohort, education, and income. Further adjustment for adult BMI at study enrollment completely eliminated the associations of age at menarche (HR = 0.99, 0.96-1.02) and the leg length-to-sitting-height ratio (HR = 1.00, 0.91-1.10 for men; HR = 1.01, 0.96-1.07 for women) with diabetes risk.Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leg-length-to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity.

BackgroundPrevious studies have suggested that marital status is associated with mortality, but few studies have been conducted in China where increasing aging population and divorce rates may have major impact on health and total mortality.MethodsWe examined the association of marital status with mortality using data from the Shanghai Women's Health Study (1996-2009) and Shanghai Men's Health Study (2002-2009), two population-based cohort studies of 74,942 women aged 40-70 years and 61,500 men aged 40-74 years at the study enrollment. Deaths were identified by biennial home visits and record linkage with the vital statistics registry. Marital status was categorized as married, never married, divorced, widowed, and all unmarried categories combined. Cox regression models were used to derive hazard ratios (HR) and 95% confidence interval (CI).ResultsUnmarried and widowed women had an increased all-cause HR = 1.11, 95% CI: 1.03, 1.21 and HR = 1.10, 95% CI: 1.02, 1.20 respectively) and cancer (HR = 1.17, 95% CI: 1.04, 1.32 and HR = 1.18, 95% CI: 1.04, 1.34 respectively) mortality. Never married women had excess all-cause mortality (HR = 1.46, 95% CI: 1.03, 2.09). Divorce was associated with elevated cardiovascular disease (CVD) mortality in women (HR = 1.47, 95% CI: 1.01, 2.13) and elevated all-cause mortality (HR = 2.45, 95% CI: 1.55, 3.86) in men. Amongst men, not being married was associated with excess all-cause (HR = 1.45, 95% CI: 1.12, 1.88) and CVD (HR = 1.65, 95% CI: 1.07, 2.54) mortality.ConclusionsMarriage is associated with decreased all cause mortality and CVD mortality, in particular, among both Chinese men and women.

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.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

The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15-2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39-2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13-1.48) risk of death from all-causes and 91% increased (95%CI: 1.41-2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12-3.33) compared with non-diabetic patients.The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts.

Although cigarette smoking, excessive alcohol drinking, obesity, and several other well-studied unhealthy lifestyle-related factors each have been linked to the risk of multiple chronic diseases and premature death, little is known about the combined impact on mortality outcomes, in particular among Chinese and other non-Western populations. The objective of this study was to quantify the overall impact of lifestyle-related factors beyond that of active cigarette smoking and alcohol consumption on all-cause and cause-specific mortality in Chinese women.We used data from the Shanghai Women's Health Study, an ongoing population-based prospective cohort study in China. Participants included 71,243 women aged 40 to 70 years enrolled during 1996-2000 who never smoked or drank alcohol regularly. A healthy lifestyle score was created on the basis of five lifestyle-related factors shown to be independently associated with mortality outcomes (normal weight, lower waist-hip ratio, daily exercise, never exposed to spouse's smoking, higher daily fruit and vegetable intake). The score ranged from zero (least healthy) to five (most healthy) points. During an average follow-up of 9 years, 2,860 deaths occurred, including 775 from cardiovascular disease (CVD) and 1,351 from cancer. Adjusted hazard ratios for mortality decreased progressively with an increasing number of healthy lifestyle factors. Compared to women with a score of zero, hazard ratios (95% confidence intervals) for women with four to five factors were 0.57 (0.44-0.74) for total mortality, 0.29 (0.16-0.54) for CVD mortality, and 0.76 (0.54-1.06) for cancer mortality. The inverse association between the healthy lifestyle score and mortality was seen consistently regardless of chronic disease status at baseline. The population attributable risks for not having 4-5 healthy lifestyle factors were 33% for total deaths, 59% for CVD deaths, and 19% for cancer deaths.In this first study, to our knowledge, to quantify the combined impact of lifestyle-related factors on mortality outcomes in Chinese women, a healthier lifestyle pattern-including being of normal weight, lower central adiposity, participation in physical activity, nonexposure to spousal smoking, and higher fruit and vegetable intake-was associated with reductions in total and cause-specific mortality among lifetime nonsmoking and nondrinking women, supporting the importance of overall lifestyle modification in disease prevention. Please see later in the article for the Editors' Summary.

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r(2)

Genetic factors play an important role in the etiology of breast cancer. We carried out a multi-stage genome-wide association (GWA) study in over 28,000 cases and controls recruited from 12 studies conducted in Asian and European American women to identify genetic susceptibility loci for breast cancer. After analyzing 684,457 SNPs in 2,073 cases and 2,084 controls in Chinese women, we evaluated 53 SNPs for fast-track replication in an independent set of 4,425 cases and 1,915 controls of Chinese origin. Four replicated SNPs were further investigated in an independent set of 6,173 cases and 6,340 controls from seven other studies conducted in Asian women. SNP rs4784227 was consistently associated with breast cancer risk across all studies with adjusted odds ratios (95% confidence intervals) of 1.25 (1.20-1.31) per allele (P = 3.2 x 10(-25)) in the pooled analysis of samples from all Asian samples. This SNP was also associated with breast cancer risk among European Americans (per allele OR = 1.19, 95% CI = 1.09-1.31, P = 1.3 x 10(-4), 2,797 cases and 2,662 controls). SNP rs4784227 is located at 16q12.1, a region identified previously for breast cancer risk among Europeans. The association of this SNP with breast cancer risk remained highly statistically significant in Asians after adjusting for previously-reported SNPs in this region. In vitro experiments using both luciferase reporter and electrophoretic mobility shift assays demonstrated functional significance of this SNP. These results provide strong evidence implicating rs4784227 as a functional causal variant for breast cancer in the locus 16q12.1 and demonstrate the utility of conducting genetic association studies in populations with different genetic architectures.