Shanghai Women's Health Study Research Articles

A nested case-control study of untargeted plasma metabolomics and lung cancer among never-smoking women within the prospective Shanghai Women's Health Study.

The etiology of lung cancer in never-smokers remains elusive, despite 15% of lung cancer cases in men and 53% in women worldwide being unrelated to smoking. Here, we aimed to enhance our understanding of lung cancer pathogenesis among never-smokers using untargeted metabolomics. This nested case-control study included 395 never-smoking women who developed lung cancer and 395 matched never-smoking cancer-free women from the prospective Shanghai Women's Health Study with 15,353 metabolic features quantified in pre-diagnostic plasma using liquid chromatography high-resolution mass spectrometry. Recognizing that metabolites often correlate and seldom act independently in biological processes, we utilized a weighted correlation network analysis to agnostically construct 28 network modules of correlated metabolites. Using conditional logistic regression models, we assessed the associations for both metabolic network modules and individual metabolic features with lung cancer, accounting for multiple testing using a false discovery rate (FDR) < 0.20. We identified a network module of 121 features inversely associated with all lung cancer (p = .001, FDR = 0.028) and lung adenocarcinoma (p = .002, FDR = 0.056), where lyso-glycerophospholipids played a key role driving these associations. Another module of 440 features was inversely associated with lung adenocarcinoma (p = .014, FDR = 0.196). Individual metabolites within these network modules were enriched in biological pathways linked to oxidative stress, and energy metabolism. These pathways have been implicated in previous metabolomics studies involving populations exposed to known lung cancer risk factors such as traffic-related air pollution and polycyclic aromatic hydrocarbons. Our results suggest that untargeted plasma metabolomics could provide novel insights into the etiology and risk factors of lung cancer among never-smokers.

Sex-specific impact of dietary patterns on liver cancer incidence: updated results from two population-based cohort studies in China.

The associations between dietary patterns and liver cancer risk have received much attention, but evidence among the Chinese population is scarce. This study aims to update the results of two cohort studies and provide the sex-specific associations in the Chinese population. This study was based on two cohorts from the Shanghai Men's Health Study (SMHS) and the Shanghai Women's Health Study (SWHS). Diet information was collected by validated food frequency questionnaires. Dietary patterns were derived by factor analysis. Cox regression model was utilized to estimate the hazard ratio (HR) and 95% confidence interval (CI) for associations between dietary patterns and liver cancer risk. During median follow-up years of 11.2 (male) and 17.1 (female) years, 427 males and 252 females were identified as incident primary liver cancer cases. In males, vegetable-based dietary pattern was inversely associated with liver cancer (HRQ4-Q1: 0.67, 95%CI 0.51-0.88, Ptrend < 0.001). Interaction analysis indicated that in males lower vegetable-based dietary pattern score and older age/medical history of chronic hepatitis combined increase the hazard of liver cancer more than the sum of them, with a 114% and 1061% higher risk, respectively. In females, the fruit-based dietary pattern was associated with a reduced risk of liver cancer (HRQ4-Q1: 0.63, 95%CI 0.42-0.95, Ptrend = 0.03). In both males and females, null associations were observed between the meat-based dietary pattern and the risk of liver cancer. A vegetable-based dietary pattern in males and a fruit-based dietary pattern in females tended to have a protective role on liver cancer risk. This study provided updated information that might be applied to guide public health action for the primary prevention of liver cancer.

Choice and application of time scale selection for Cox proportional hazards regression model in cohort studies

Cox proportional hazards regression model (Cox model) is the most commonly used multivariate approach in time-to-event data analysis. A vital issue in fitting Cox model is choosing the appropriate time scale related to the occurrence of the outcome events. However, few domestic studies have focused on selecting and applying time scales for Cox model in the analysis of cohort study data. This study briefly introduced and compared several time scales in the reports from literature; and used data from the Shanghai Women's Health Study to illustrate the impact of different time scales on data analysis results, using the association between central obesity and the risk of liver cancer as an example. On this basis, several suggestions on selecting time scales in Cox model are proposed to provide a reference for the analysis of cohort study data.

Associations of lifestyle with physical, hearing, visual, and mental functional impairments among older adults: Findings from two prospective cohort studies

ObjectiveTo examine the associations between lifestyle habits and functional impairments among older adults. MethodsThe study includes 20,545 women and 14,374 men aged 70 years or older at the time of the function assessment. Participants were from two prospective cohort studies: the Shanghai Women's Health Study (SWHS, enrollment from 1996 to 2000) and the Shanghai Men's Health Study (SMHS, enrollment from 2002 to 2006). Lifestyle information was collected at study enrollment and a healthy lifestyle score (HLS) was derived. Functional impairment information was collected at the follow-up survey conducted in 2012-2017. Logistic regression analyses were applied to estimate the associations of HLS with functional impairments. ResultsThe average age at lifestyle and functional impairment assessment was 62.3 (range: 49.9-70.9) and 77.7 (range: 70.0-89.4) for women and 67.5 (range: 55.1-74.9) and 77.4 (range: 70.0-88.6) for men. After a median follow-up of 14.4 years, we found that the HLS was inversely associated with overall severe functional impairment: odds ratio (95% confidence interval), 0.78(0.71-0.86) and individual severe functional impairment: 0.67(0.62-0.73) for independent walking, 0.85(0.77-0.94) for hearing/vision, 0.79(0.70-0.88) for memory, and 0.74(0.67-0.82) for decision-making impairment, comparing the highest with the lowest HLS categories. Such associations were similar among individuals with/without cardiometabolic diseases at baseline. The associations between each lifestyle factor and functional impairments differed. ConclusionA healthy lifestyle was associated with reduced odds of physical and mental impairment among older Chinese adults, emphasizing the importance of promoting and maintaining a healthy lifestyle to prevent or postpone age-related functional impairments.

Cumulative consumption of tea is associated with lower risk of liver cancer: Updated results from the Shanghai Women's Health Study.

Prospective epidemiological studies have provided limited evidence for an association between tea consumption and liver cancer risk. Based on a population-based prospective cohort study in middle-aged Chinese women, we investigated the association between tea consumption and the risk of primary liver cancer. Detailed information on tea drinking habits and other potential confounders was obtained at the baseline interview. Incident liver cancer cases were identified through record linkage with the population-based cancer registry and verified through home visits and review of medical charts by medical experts. Multiple aspects of tea drinking habits including starting age, duration, intensity and cumulative consumption of any type of tea and green tea were considered. Multivariable-adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) were derived from the Cox regression models. After a median follow-up time of 18.12 (interquartile range=1.59) years, 253 incident liver cancer cases were identified from 71 841 cohort members. Compared with never tea drinkers, the risk of liver cancer for participants who have consumed over 30 kg of dried tea leaves cumulatively was 0.56 (95% CI: 0.32-0.97). For those who drank green tea only, the aHR was 0.54 (95% CI: 0.30-0.98). This updated study suggested an inverse association between cumulative consumption of tea, especially green tea and the risk of primary liver cancer.

Association of Ginseng Consumption With All-cause and Cause-specific Mortality: Shanghai Women's Health Study.

BackgroundGinseng, an herbal remedy, has been commonly used in Asian countries to promote longevity and health for over 2,000 years. However, the association of ginseng consumption with all-cause and cause-specific mortality is still unclear. We analyzed the association of total and major cause-specific mortality (cardiovascular disease [CVD], cancer, and other death) with consumption of ginseng (primarily American and white ginseng).MethodsThis study included 56,183 female participants with an average follow-up of 14.7 years in the Shanghai Women’s Health Study, an ongoing prospective cohort study. Data were assessed via an in-person interview conducted at baseline recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for ginseng-mortality associations after adjusting for confounders.ResultsCompared with those who never used ginseng, regular ginseng use was associated with significantly reduced all-cause mortality (HR 0.92; 95% CI, 0.87–0.98). This inverse association was seen primarily among those who consumed ginseng for perceived general health benefit (HR 0.90; 95% CI, 0.85–0.96). A significant dose-response association was observed between duration of ginseng use and total mortality (HR 0.85, for using ≥6 years vs never use; P for trend <0.001), CVD mortality (HR 0.83; P for trend = 0.019), and other-cause mortality (HR 0.76; P for trend = 0.001). However, no dose-response association was observed between amount of ginseng consumption and mortality outcomes.ConclusionRegular ginseng consumption, particularly over a long duration, was associated with decreased risk of all causes of death, death due to CVD, and death due to certain other diseases.

Urine biomarkers enable pancreatic cancer detection up to 2 years before diagnosis.

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is mainly attributed to late diagnosis. We assessed the predictive performance of our previously reported urine biomarker panel for earlier detection of PDAC (LYVE1, REG1B and TFF1) in prediagnostic samples, alone and in combination with plasma CA19-9. This nested case-control study included 99 PDAC cases with urine samples prospectively collected up to 5 years prior to PDAC diagnosis and 198 matched controls. The samples were obtained from the Shanghai Women's Health Study (SWHS), the Shanghai Men's Health Studies (SMHS) and the Southern Community Cohort Study (SCCS). The urine biomarkers were measured by ELISA. Plasma CA19-9 was quantified by Luminex. Multiple logistic regression and Wilcoxon rank-sum and Mann-Whitney test were used for analysis. The internal validation approach was applied and the validated AUC estimators are reported on. The algorithm of urinary protein panel, urine creatinine and age named PancRISK, displayed similar AUC as CA19-9 up to 1year before PDAC diagnosis (AUC=0.79); however, the combination enhanced the AUCs to 0.89, and showed good discriminative ability (AUC=0.77) up to 2 years. The combination showed sensitivity (SN) of 72% at 90% specificity (SP), and SP of 59% at 90% SN up to 1year and 60% SN with 80% SP and 53% SP with 80% SN up to 2 years before PDAC diagnosis. Adding the clinical information on BMI value resulted in the overall improvement in performance of the PancRISK score. When combined with CA19-9, the urinary panel reached a workable model for detecting PDAC cases up to 2 years prior to diagnosis.

Isoflavone and soy food intake and risk of lung cancer in never smokers: report from prospective studies in Japan and China.

Evidence from several cohorts has suggested that a higher intake of isoflavone is associated with lower risk of lung cancer in never smokers, but the association has not been investigated by histologic type of lung cancer. Adenocarcinoma is a common histologic type found in never smokers. We hypothesized that a higher intake of isoflavone is associated with a lower risk of lung adenocarcinoma among never smokers. Here, we examined the associations of isoflavone and soy food intake with lung cancer and its histologic types in never smokers. We performed a pooled analysis using data from the Japan Public Health Center-based Prospective Study, Shanghai Women's Health Study and Shanghai Men's Study with 147,296 never smokers aged 40-74years with no history of cancer. During 1,990,040 person-years of follow-up, 1247 lung cancer cases were documented. Dietary isoflavone and soy food intake were assessed using a food-frequency questionnaire. Multivariable Cox proportional hazards models assessed the associations between isoflavone and soy intake with incidence of lung cancer by histologic type. A higher intake of dietary isoflavone and soy food were associated with reduced risk of lung adenocarcinoma. The multivariable hazard ratios (HRs) (95% CI) of risk of lung adenocarcinoma for the highest versus lowest intakes of isoflavone and soy food were 0.74 (0.60-0.92) and 0.78 (0.63-0.96), respectively. The multivariable HRs of risk of lung adenocarcinoma associated with each 10mg/day increase in isoflavone and each 50g/day increase in soy food intake were 0.81 (0.70-0.94) and 0.84 (0.73-0.96), respectively. Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers.

Quality of dietary carbohydrate is more important than its quantity in lipid peroxidation

High glycemic index (GI) diets have been linked to elevated risk of cardiometabolic diseases. One possible underlying mechanism comes from high GI diet's potential to promote lipid peroxidation. We aim to evaluate whether and to what extent dietary carbohydrate quality and quantity are associated with systemic levels of lipid peroxidation in females. In this cross-sectional analysis of 2163 middle-aged women, a subset of the Shanghai Women's Health Study, we measured lipid peroxidation biomarkers F2-isoprostanes (F2-IsoPs) and its metabolite, 2,3-dinor-5,6-dihydro-15-F2t-IsoP (F2-IsoP-M), in urine. The quality of carbohydrate was defined by dietary GI, assessed using a validated FFQ via in-person interviews. A multivariable linear regression model with restricted cubic spline functions was used to evaluate the association of measured biomarkers with carbohydrate intake and dietary GI. After adjustment for potential confounding factors such as cigarette smoking, BMI, and comorbidities, among others, we found that F2-IsoP-M concentrations were positively associated with both carbohydrate intake and dietary GI. Carbohydrate intake and dietary GI were weakly correlated (r=0.12). When further mutually adjusted for the 2 factors, the positive association with F2-IsoP-M remained statistically significant for GI (P=0.004) but not for carbohydrate intake (P=0.50). Compared with those in the 10th percentile of dietary GI, fold increases (95% CI) in F2-IsoP-M concentrations for those in the 30th, 50th, 70th, and 90th percentiles were 1.03 (1.00, 1.07), 1.06 (1.01, 1.10), 1.09 (1.03, 1.14), and 1.13 (1.05, 1.21), respectively. Moreover, there appeared a threshold regarding the association between dietary GI and F2-IsoP-M concentrations, with the dose-effect slope of GI being 2.3 times greater when GI was≥75 relative to GI<75. This study provides evidence that the quality of dietary carbohydrate may be more important than the quantity of the intake with regard to systemic lipid peroxidation.

Tea Consumption and Gut Microbiome in Chinese Men and Women

Abstract Objectives To evaluate the associations of tea drinking habits with gut microbiome diversity and composition among senior Chinese adults. Methods Included in the study were 1179 men and 1078 women from the Shanghai Men's Health Study and Shanghai Women's Health Study who were free of cancer, cardiovascular disease, and diabetes at stool collection (2015–2018) and had no diarrhea or antibiotic use in the last 7 days before stool collection. The gut microbiome was profiled by 16S rRNA sequencing. Tea drinking habits were assessed at the cohorts’ baseline and follow-up surveys (1996–2011), including status (current or not), type (green tea or others), amount (tertile cutoffs: 2 and 3.3 cups/day in men; 1.3 and 2 cups/day in women), and duration (tertile cutoffs: 30.8 and 41.0 years in men; 15.1 and 32.8 years in women). The associations of tea variables with microbiome diversity and taxa abundance were evaluated by linear or negative binomial hurdle models after appropriate data transformation and adjusting for age, education, income, tobacco smoking, alcohol drinking, physical activity, body mass index, diet quality score, and hypertension status. False discovery rate &amp;lt; 0.1 at each taxonomic level was considered statistically significant. Results The mean ± SD age at stool collection was 67.2 ± 9.0 years in men and 69.6 ± 8.5 years in women. None of the tea drinking variables showed significant association with microbiome ɑ-diversity in men or women; however, tea drinking status, type, amount, and duration were all significantly associated with β-diversity (Bray–Curtis distance) in men (P &amp;lt; 0.001). Significant associations with taxa abundance were also observed only in men. Current tea drinking, particularly green tea drinking, was associated with increased abundance of order Synergistales and class Mollicutes and its order RF39 (PFDR &amp;lt; 0.10). In addition, increased abundance of families Coriobacteriaceae, Odoribacteraceae and genera Collinsella, Odoribacter were observed among men who drank &amp;gt;3.3 cups per day (high amount vs. non-drinkers). Conclusions Tea drinking may affect gut microbiome β-diversity and abundance of some bacteria in Chinese men. Future studies are needed to examine the potential sex-specific effect of tea drinking on gut microbiome and the role of these bacteria in mediating the health benefits of tea. Funding Sources The National Institutes of Health.

Endogenous sex hormones, aromatase activity and lung cancer risk in postmenopausal never-smoking women.

Although reproductive factors have been repeatedly associated with lung cancer risk, no study to date has directly evaluated the relationship with endogenous sex hormones nor with aromatase activity in postmenopausal never-smoking women. A case-control study of 397 incident lung cancer cases and their individually matched controls, nested within the Shanghai Women's Health Study, was conducted among postmenopausal women who were lifetime never smokers. Prediagnostic concentrations of sex hormones was quantitated using LC-MS/MS assays in plasma. The product-substrate molar ratio of estrone to androstenedione was used as an index of aromatase activity (IAA). Multivariable conditional logistic regression models were used to calculate odds ratios (ORs) for lung cancer. Baseline concentrations of estradiol, free testosterone and IAA were inversely associated with subsequent risk of lung cancer in multivariable-adjusted models. When further adjusted for body mass index, the inverse association with estradiol was attenuated and no longer statistically significant, but the association with free testosterone and IAA remained. In analyses confined to participants having never used menopausal hormone therapy in 376 case-control pairs, the inverse association with free testosterone and IAA was slightly strengthened. OR for the highest vs the lowest quartile of free testosterone was 0.55 (95% CI=0.34-0.90; Ptrend =.03), and the corresponding OR for IAA was 0.57 (95% CI=0.34-0.96; Ptrend =.04). Our study, for the first time, suggests that higher levels of circulating free testosterone and estimated aromatase activity may be associated with lower lung cancer risk in postmenopausal never-smoking women.

Statistical methods for relative risk estimation and applications in case-cohort study

Objective: To systematically introduce the design of case-cohort study and the statistical methods of relative risk estimation and their application in the design. Methods: First, we introduced the basic principles of case-cohort study design. Secondly, Prentice's method, Self-Prentice method and Barlow method were described in the weighted Cox proportional hazard regression models in detail, finally, the data from the Shanghai Women's Health Study were used as an example to analyze the association between obesity and liver cancer incidence in the full cohort and case-cohort sample, and the results of parameters from each method were compared. Results: Significant association was observed between obesity and risk for liver cancer incidence in women in both the full cohort and the case-cohort sample. In the Cox proportional hazard regression model, the partial regression coefficients of the full cohort and the case-cohort sample fluctuated with the adjustment of confounding factors, but the hazard ratio estimates of them were close. There was a difference in the standard error of the partial regression coefficient between the full cohort and the case-cohort sample. The standard error of the partial regression coefficient of the case-cohort sample was larger than that of the full cohort, resulting in a wider 95% confidence interval of the relative risk. In the weighted Cox proportional hazard regression model, the standard error of the partial regression coefficient of Prentice's method was closer to the parameter estimates from full cohort than Self-Prentice method and Barlow method, and the 95% confidence interval of hazard ratio was closer to that of the full cohort. Conclusions: Case-cohort design could yield parameter results closer to the full cohort by collecting and analyzing data from sub-cohort members and patients with the disease, and reduce sample size and improve research efficiency. The results suggested that Prentice's method would be preferred in case-cohort design.

Association between Tea Consumption and Hypertension Risk among Middle-Aged and Older Chinese Adults

BackgroundCurrent evidence on tea consumption and hypertension is inconclusive, and prospective studies among habitual tea drinkers remain limited. ObjectiveWe investigated the associations of habitual tea consumption with hypertension risk and longitudinal blood pressure changes in 2 large cohorts. MethodsThis study included participants aged 40–75 y from the Shanghai Women's Health Study (n = 31,351) and the Shanghai Men's Health Study (n = 28,342), without hypertension, diabetes, cardiovascular disease, or cancer at baseline. Information on tea consumption was assessed during in-person interviews at enrollment and follow-up visits. Incident hypertension was identified by self-reported diagnosis, medication use, or blood pressure measurements. ResultsCurrent tea drinkers had a 7% higher risk than the non–current tea drinker group [HRs (95% CIs): women, 1.07 (1.01, 1.14); men, 1.07 (1.02, 1.12)]. The amount of tea drinking showed significant dose–response associations with hypertension: compared with the non-current group, HRs (95% CIs) for women and men were 1.01 (0.90, 1.14) and 1.02 (0.96, 1.08) for low (women/men: <100/200 g/mo), 1.07 (1.01, 1.15) and 1.05 (0.99, 1.12) for medium (women/men: 100–250/200–250 g/mo), and 1.18 (1.01, 1.39) and 1.10 (1.03, 1.17) for the high-amount group (women/men: >250 g/mo). Among participants without hypertension, compared with non–current tea drinkers, least-squares means of 3-y changes in blood pressure were 0.3–0.4 mm Hg higher for women and men as current drinkers and 0.7–0.9 mm Hg higher for men in the high-consumption group. Compared with those who never drank tea, women who drank tea consistently had 0.5 (0.2, 0.7) mm Hg higher diastolic blood pressure (DBP), whereas men had 0.5 (0.04, 0.9) mm Hg higher systolic blood pressure and 0.3 (0.04, 0.6) mm Hg higher DBP, respectively. ConclusionsOur findings suggest that habitual tea drinking is associated with a slightly higher risk of hypertension and a minor increase in blood pressure among middle-aged and older Chinese adults, which warrants confirmation by long-term intervention studies.

252Development and validation of a breast cancer absolute risk prediction model in Chinese population

Abstract Background Compared with developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate, lower survival rate, and vast geographic variation. However, there is no national validated model in China to aid early detection yet. Methods A large nation-wide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks. A total of 300,824 women free of prior cancer were recruited during 2004-2008 and followed up to 31 December 2016. Absolute risks were calculated by incorporating national age- and residence-specific incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women's Health Study (SWHS), to externally validate the calibration and discriminating accuracy. Results During a median of 10.2 years of follow-up in the CKB, 2,287 cases were observed. The final model included education, BMI, height, family history of cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed ratios of 1.00 (95% confidence interval (CI), 0.96-1.04) and 0.94 (95% CI, 0.89-0.99), respectively. After eliminating the effect of age and residence, the adjusted areas under the curve were 0.615 (95% CI, 0.600-0.630) and 0.585 (95% CI, 0.564-0.605), respectively. Conclusions Based only on non-laboratory predictors, our model has an excellent calibration and moderate discriminating capacity. The model may be a useful tool to raise individuals’ awareness and aid risk-stratified screening and prevention strategies. Key messages We developed a breast cancer prediction model for Chinese women, which performed well in internal and external validation.

Legume Consumption and Gut Microbiome in Elderly Chinese Men and Women.

Legumes, important components of a healthy diet, may exert their health benefits through the influence of the gut microbiome. However, this hypothesis has not been well investigated. This study aimed to examine the associations between long-term legume consumption and the gut microbiome among elderly Chinese. The gut microbiome was profiled by 16S ribosomal RNA sequencing in 2302 Chinese adults enrolled in 2 large cohort studies, the Shanghai Women's Health Study and Shanghai Men's Health Study. Legume consumption, including peanuts, soy foods, and other beans, was assessed by food-frequency questionnaires prior to the stool collection. The associations of legume consumption with microbiome diversity and taxa abundance were evaluated by linear or negative binomial hurdle models, adjusting for sociodemographics, lifestyle factors, and BMI. False discovery rate (FDR)-corrected P values (PFDR) < 0.1 were considered significant. Respectively, 52% and 48% of study participants were male and female. The mean age at stool collection was 68.03 y for females and 70.28 y for males. Total legume consumption was not associated with gut microbiome ɑ-diversity; however, male peanut consumers had a higher Chao1 index (β = 22.52, P=0.01), whereas peanut consumption was associated with decreased Shannon (β = -0.03, P=0.02) and Simpson (β = -0.002, P=0.04) indexes among females. In female and male combined analyses, total legume consumption was associated with increased Enterobacteriales (β = 0.30, PFDR=0.06). Within this order, an unclassified genus in the family Enterobacteriaceae was positively associated with total legume (β = 0.46, PFDR=0.03) and peanut (β = 0.59, PFDR=0.01) consumption. Stratified analyses showed significant associations were primarily confined to females and participants without metabolic conditions. Legume consumption was associated with gut microbiome diversity and abundance of some bacteria in elderly Chinese. Associations were significant only among 1 sex group. Further research, including large-scale prospective studies and feeding trials, is needed to fully understand the role of the gut microbiome in legume-health associations.

Soy Intake and Colorectal Cancer Risk: Results from a Pooled Analysis of Prospective Cohort Studies Conducted in China and Japan

Soy is commonly consumed in east Asian countries and is suggested to reduce colorectal cancer (CRC) risk. However, results from epidemiologic studies are inconsistent, despite the anti-inflammatory and antiproliferative properties of soy isoflavones and soy protein. We evaluated the association between soy isoflavones and soy protein and CRC risk using 4 prospective cohort studies from China and Japan. Data were pooled from the Shanghai Women's Health Study (SWHS), Shanghai Men's Health Study (SMHS), Japan Public Health Center-based Prospective Study Cohort 1 (JPHC1), and Cohort 2 (JPHC2). Cox proportional hazards models estimated HRs and corresponding 95% CIs for the association of soy protein and isoflavone intake with CRC risk. The study included 205,060 individuals, among whom 2971 were diagnosed with incident CRC over an average follow-up of 12.7 y. No statistically significant associations with CRC risk were observed for soy protein or isoflavone intake. No association was observed among ever smokers consuming higher isoflavones (HRisoflavones: 0.83; 95% CI: 0.68, 1.00) and soy protein (HRsoy protein: 0.81; 95% CI: 0.39, 1.10). However, risk reductions were observed among premenopausal women with a body mass index [BMI (kg/m2)] <23.0 at baseline for higher isoflavone (HRisoflavones: 0.58, 95% CI: 0.34, 0.98). No evidence for an overall reduction in CRC risk by increasing soy food intake (i.e., protein or isoflavones) was observed. However, the association between soy and CRC risk may vary by BMI, smoking, and menopausal status among women. Future investigations are needed to further understand the biologic mechanisms observed.

Association of Adult Weight Gain With Major Health Outcomes Among Middle-aged Chinese Persons With Low Body Weight in Early Adulthood

The association of weight gain from early to middle adulthood with disease risk has not been adequately studied. To investigate the association of adult weight gain with major health outcomes in a Chinese population with low body weight in early adulthood. This population-based cohort study assessed data from 48 377 women and 35 989 men aged 40 to 59 years at recruitment in 2 prospective cohort studies in China. The Shanghai Women's Health Study recruited 74 941 women, aged 40 to 70 years, from January 1, 1996, to December 31, 2000, and the Shanghai Men's Health Study recruited 61 482 men, aged 40 to 74 years, from January 1, 2002, to December 31, 2006. This analysis was conducted from September 1, 2017, to April 30, 2018. Weight gain from 20 years of age to 40 to 59 years of age. Mortality and incidence of cancers and other chronic diseases. This analysis included 48 377 women (mean [SD] age, 47.8 [5.3] years) and 35 989 men (mean [SD] age, 49.6 [5.1] years). Per 5-kg weight gain from early to middle adulthood was associated with an approximately 10% (hazard ratio [HR], 1.09; 95% CI, 1.04-1.14 for men; HR, 1.14; 95% CI, 1.11-1.19 for women) elevated all-cause mortality and a greater than 20% (HR, 1.26; 95% CI, 1.16-1.38 for men; HR, 1.23; 95% CI, 1.14-1.33 for women) cardiovascular disease-related mortality in later life among individuals who reached a body mass index (BMI) of 23 or higher at middle adulthood. Body mass index at middle adulthood also modified the association of weight gain with risk of obesity-related cancers, with weight gain of 20 kg or more associated with increased risks both for men (HR, 1.34; 95% CI, 1.07-1.67) and for women (HR 1.45; 95% CI, 1.24-1.68). No similar associations were found for individuals with a BMI of 18.5 to 22.9. Regardless of BMI, weight gain was associated with elevated risks of type 2 diabetes, hypertension, fatty liver disease, stroke, gout, and gallstones, particularly for type 2 diabetes (HR, 7.87; 95% CI, 6.91-8.97 for women; HR, 4.95; 95% CI, 4.23-5.79 for men) and fatty liver disease (HR, 3.68; 95% CI, 3.42-3.95 for women; HR, 2.83, 95% CI, 2.56-3.13 for men) in individuals with weight gain of 20 kg or more compared with those with a healthy weight. This study found that weight gain from early to middle adulthood was associated with disease incidence and mortality in later life. The BMI at middle adulthood modified the association of weight gain with mortality and cancer incidence but not risk of other major chronic diseases.

Urinary PGE-M Levels and Risk of Ovarian Cancer.

Regular aspirin use may lower ovarian cancer risk by blocking the cyclooxygenase enzymes, resulting in lower expression of prostaglandins, including prostaglandin E2 (PGE2). We evaluated whether higher prediagnosis PGE-M (a urinary biomarker of PGE2) was associated with increased ovarian cancer risk in three prospective cohorts. We conducted a case-control study nested in the Nurses' Health Study (NHS), NHSII, and Shanghai Women's Health Study. Our analyses included 304 cases of epithelial ovarian cancer diagnosed from 1996 to 2015 and 600 matched controls. We measured urinary PGE-M using LC/MS with normalization to creatinine. Measures from each study were recalibrated to a common standard. We estimated ORs and 95% confidence intervals (CI) using conditional logistic regression, with PGE-M levels modeled in quartiles. Multivariable models were adjusted for ovarian cancer risk factors. There was no evidence of an association between urinary PGE-M levels and ovarian cancer risk for women with PGE-M levels in the top versus bottom quartile (OR = 0.80; 95% CI, 0.51-1.27; P trend = 0.37). We did not observe heterogeneity by histotype (P = 0.53), and there was no evidence of effect modification by body mass index (P interaction = 0.82), aspirin use (P interaction = 0.59), or smoking (P interaction = 0.14). Prediagnosis urinary PGE-M levels were not significantly associated with ovarian cancer risk. Larger sample sizes are needed to consider a more modest association and to evaluate associations for specific tumor subtypes. Systemic prostaglandin levels do not appear strongly associated with ovarian cancer risk. Future research into aspirin use and ovarian cancer risk should consider local prostaglandins and prostaglandin-independent mechanisms.

Association of Untargeted Urinary Metabolomics and Lung Cancer Risk Among Never-Smoking Women in China

Chinese women have the highest rate of lung cancer among female never-smokers in the world, and the etiology is poorly understood. To assess the association between metabolomics and lung cancer risk among never-smoking women. This nested case-control study included 275 never-smoking female patients with lung cancer and 289 never-smoking cancer-free control participants from the prospective Shanghai Women's Health Study recruited from December 28, 1996, to May 23, 2000. Validated food frequency questionnaires were used for the collection of dietary information. Metabolomic analysis was conducted from November 13, 2015, to January 6, 2016. Data analysis was conducted from January 6, 2016, to November 29, 2018. Untargeted ultra-high-performance liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance metabolomic profiles were characterized using prediagnosis urine samples. A total of 39 416 metabolites were measured. Incident lung cancer. Among the 564 women, those who developed lung cancer (275 participants; median [interquartile range] age, 61.0 [52-65] years) and those who did not develop lung cancer (289 participants; median [interquartile range] age, 62.0 [53-66] years) at follow-up (median [interquartile range] follow-up, 10.9 [9.0-11.7] years) were similar in terms of their secondhand smoke exposure, history of respiratory diseases, and body mass index. A peak metabolite, identified as 5-methyl-2-furoic acid, was significantly associated with lower lung cancer risk (odds ratio, 0.57 [95% CI, 0.46-0.72]; P < .001; false discovery rate = 0.039). Furthermore, this peak was weakly correlated with self-reported dietary soy intake (ρ = 0.21; P < .001). Increasing tertiles of this metabolite were associated with lower lung cancer risk (in comparison with first tertile, odds ratio for second tertile, 0.52 [95% CI, 0.34-0.80]; and odds ratio for third tertile, 0.46 [95% CI, 0.30-0.70]), and the association was consistent across different histological subtypes and follow-up times. Additionally, metabolic pathway analysis found several systemic biological alterations that were associated with lung cancer risk, including 1-carbon metabolism, nucleotide metabolism, oxidative stress, and inflammation. This prospective study of the untargeted urinary metabolome and lung cancer among never-smoking women in China provides support for the hypothesis that soy-based metabolites are associated with lower lung cancer risk in never-smoking women and suggests that biological processes linked to air pollution may be associated with higher lung cancer risk in this population.

Serum ghrelin and esophageal and gastric cancer in two cohorts in China.

Ghrelin is a hormone produced in the oxyntic glands of the stomach. Previous work by our group has suggested that serum ghrelin concentrations are inversely associated with gastric and esophageal cancer risk. We measured ghrelin concentrations in the Linxian General Population Nutrition Intervention Trial (NIT), and the Shanghai Women's Health Study (SWHS). In NIT, we analyzed serum samples from 298 esophageal squamous cell carcinoma (ESCC) cases, 518 gastric cardia adenocarcinoma (GCA) cases, 258 gastric noncardia adenocarcinoma (GNCA) cases and 770 subcohort controls (case-cohort). In SWHS, we measured ghrelin in plasma samples from 249 GNCA cases and 498 matched controls (nested case-control). Ghrelin was measured using radioimmunoassay. In NIT and SWHS, low ghrelin concentrations were associated with an increased risk of developing GNCA and GCA. The hazard ratio (HR Q1:Q4 ) for GNCA in NIT was 1.35 (95% CI: 0.89-2.05; p-trend = 0.02); the odds ratio in SWHS was 1.66 (95% CI: 1.02-2.70; p-trend = 0.06). Low ghrelin was associated with a twofold increase of GCA (HR Q1:Q4 = 2.00, 95% CI: 1.45-2.77; p-trend<0.001). In contrast, a lower risk of ESCC (NIT ESCC HR Q1:Q4 = 0.65, 95% CI: 0.45-0.92; p-trend = 0.02) was found in NIT. Low baseline ghrelin concentrations were associated with an increased risk for GNCA and GCA in the NIT and the SWHS. In contrast, low ghrelin concentrations at baseline were associated with a reduced risk of developing ESCC in the NIT. Ghrelin may be an early marker of future cancer risk for developing upper gastrointestinal cancer in regions of high incidence.