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Simple Summary: Studies on circulating protein for colorectal cancer risk in a prospective study design is lacking. The aim of the present study was to scan and identify the protein markers by using proteomics technologies in a two-stage case-control study nested within the Shanghai Women's Health Study (SWHS), a population-based prospective cohort study. In the discovery set, we found 27 circulating proteins with a nominally significant association. Six of them, including CD79B, DDR1, EFNA4, FLRT2, LTA4H, and NCR1, were validated in the validation phase of the study. This study is the first to evaluate over 1000 circulating proteins in prediagnostic blood samples for their associations with CRC risk in East Asians. Background: Proteomics-based technologies are emerging tools used for cancer biomarker discovery. Limited prospective studies have been conducted to evaluate the role of circulating proteins in colorectal cancer (CRC) development. Methods: A two-stage case-control proteomics study nested in the Shanghai Women's Health Study was conducted. A total of 1104 circulating proteins were measured in the discovery phase, consisting of 100 incident CRC cases and 100 individually matched controls. An additional 60 case-control pairs were selected for validation. Protein profiling at both stages was completed using the Olink platforms. Conditional logistic regression was used to evaluate the associations between circulating proteins and CRC risk. The elastic net method was employed to develop a protein score for CRC risk. Results: In the discovery set, 27 proteins showed a nominally significant association with CRC risk, among which 22 were positively and 5 were inversely associated. Six of the 27 protein markers were significantly associated with CRC risk in the validation set. In the analysis of pooled discovery and validation sets, odds ratios (ORs) per standard deviation (SD) increase in levels of these proteins were 1.54 (95% confidence interval (CI): 1.15–2.06) for CD79B; 1.71 (95% CI: 1.24–2.34) for DDR1; 2.04 (95% CI: 1.39–3.01) for EFNA4; 1.54 (95% CI: 1.16–2.02) for FLRT2; 2.09 (95% CI: 1.47–2.98) for LTA4H and 1.88 (95% CI: 1.35–2.62) for NCR1. Sensitivity analyses showed consistent associations for all proteins with the exclusion of cases diagnosed within the first two years after the cohort enrollment, except for CD79B. Furthermore, a five-protein score was developed based on the six proteins identified and showed significant associations with CRC risk in both discovery and validation sets (Discovery: OR1-SD = 2.46, 95% CI: 1.53–3.95; validation: OR1-SD = 4.16, 95% CI: 1.92–8.99). Conclusions: A panel of five protein markers was identified as potential biomarkers for CRC risk. Our findings provide novel insights into the etiology of CRC and may facilitate the risk assessment of the malignancy. [ABSTRACT FROM AUTHOR]

Helicobacter pylori infection has been suggested to be associated with lung cancer risk. However, information is lacking on whether the association differs by H. pylori antigen. We conducted a nested case-control study within the Southern Community Cohort Study, including 295 incident lung cancer cases and 295 controls. Helicobacter pylori multiplex serology assay was performed to detect antibodies to 15 H. pylori proteins. Conditional logistic regression was used to estimate odds ratios (ORs) and confidence intervals (95% CIs) after adjustment for covariates. Overall H. pylori + was associated with a non-statistically significant increased risk of lung cancer (OR: 1.29; 95% CI: 0.85–1.95). Significant associations, however, were observed for H. pylori + VacA+ (OR: 1.64; 95% CI: 1.02–2.62) and H. pylori + Catalase+ (OR: 1.75; 95% CI: 1.11–2.77). The positive association of H. pylori + Catalase+ with lung cancer risk was predominantly seen among African Americans (OR: 2.09; 95% CI: 1.11–3.95) but not European Americans (OR: 1.20; 95% CI: 0.56–2.54). Among participants who smoked ≥ 30 pack-years, overall H. pylori + (OR: 1.85; 95% CI: 1.02–3.35), H. pylori + CagA+ (OR: 2.77; 95% CI: 1.35–5.70), H. pylori + VacA+ (OR: 2.53; 95% CI: 1.25–5.13) and H. pylori + HP1564+ (OR: 2.01; 95% CI: 1.07–3.77) were associated with increased risk of lung cancer. Our study provides novel evidence that associations of H. pylori infection with lung cancer risk differ by H. pylori biomarker, may be more evident among African Americans and may be modified by smoking habits. Furthermore, studies are warranted to confirm our findings. [ABSTRACT FROM AUTHOR]

Simple Summary: The risk of lung cancer associated with tooth loss has not been fully addressed, especially for the potential interaction with smoking. This cohort study with meta-analysis first investigated the association between tooth loss and lung cancer risk stratified by smoking status using the Shanghai Men's and Women's Health Studies and then summarized epidemiologic findings to date, incorporating the current study and other published studies. Our findings suggest that tooth loss is associated with an increased risk of developing lung cancer, but smoking could modify the association. A meta-analysis of eight epidemiological studies also supports a strong link of tooth loss to lung cancer risk, particularly among current smokers. Improving dental care and oral health may be an effective strategy for lung cancer prevention in addition to smoking cessation. Epidemiological evidence on tooth loss and lung cancer risk remains limited, especially for smoking-specific associations. To investigate the association between tooth loss and lung cancer risk by smoking status, we first analyzed data from the Shanghai Men's Health Study (n = 49,868) and the Shanghai Women's Health Study (n = 44,309). Cox regression models were applied to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) for lung cancer risk in relation to tooth loss. We also conducted a meta-analysis to summarize epidemiologic findings to date, incorporating results from the current study and six previously published studies. For 7.3 median follow-up years, 973 incident lung cancer cases (613 men and 360 women) were ascertained. After adjustment for major covariates, tooth loss was associated with an increased risk of lung cancer among men (HR [95% CI] for >10 teeth vs. none = 1.59 [1.21–2.11]) but not among women (0.86 [0.50–1.46]). The positive association was stronger among male current smokers (1.75 [1.26–2.45], p-interaction by smoking status = 0.04). In a meta-analysis incorporating 4052 lung cancer cases and 248,126 non-cases, tooth loss was associated with a 1.64-fold increased risk of developing lung cancer (relative risk [RR, 95% CI] for the uppermost with the lowest category = 1.64 [1.44–1.86]). The positive association was more evident among current smokers (1.86 [1.41–2.46]), but no significant associations were found among never or former smokers. Our findings suggest that tooth loss may be associated with an increased risk of lung cancer, and the association could be modified by smoking status. [ABSTRACT FROM AUTHOR]

Background Transcriptome-wide association studies have been successful in identifying candidate susceptibility genes for colorectal cancer (CRC). To strengthen susceptibility gene discovery, we conducted a large transcriptome-wide association study and an alternative splicing transcriptome-wide association study in CRC using improved genetic prediction models and performed in-depth functional investigations. Methods We analyzed RNA-sequencing data from normal colon tissues and genotype data from 423 European descendants to build genetic prediction models of gene expression and alternative splicing and evaluated model performance using independent RNA-sequencing data from normal colon tissues of the Genotype-Tissue Expression Project. We applied the verified models to genome-wide association studies (GWAS) summary statistics among 58 131 CRC cases and 67 347 controls of European ancestry to evaluate associations of genetically predicted gene expression and alternative splicing with CRC risk. We performed in vitro functional assays for 3 selected genes in multiple CRC cell lines. Results We identified 57 putative CRC susceptibility genes, which included the 48 genes from transcriptome-wide association studies and 15 genes from splicing transcriptome-wide association studies, at a Bonferroni-corrected P  value less than  .05. Of these, 16 genes were not previously implicated in CRC susceptibility, including a gene PDE7B (6q23.3) at locus previously not reported by CRC GWAS. Gene knockdown experiments confirmed the oncogenic roles for 2 unreported genes, TRPS1 and METRNL , and a recently reported gene, C14orf166. Conclusion This study discovered new putative susceptibility genes of CRC and provided novel insights into the biological mechanisms underlying CRC development. [ABSTRACT FROM AUTHOR]

Purpose: We prospectively examined associations of lung cancer risk with food intake of B vitamins involved in one-carbon metabolism and the use of folic acid-containing supplements among a low-income population of black and white adults in the Southeastern US. Methods: Within the Southern Community Cohort Study, we included 1064 incident lung cancer cases among 68,236 participants aged 40–79 years at study enrollment. Food intake and the use of folic acid-containing supplements were assessed using a validated food frequency questionnaire at study enrollment. Multivariate Cox regression was used to estimate hazards ratios (HRs) and the 95% confidence intervals (CIs). Results: Folate and/or folic acid intake from food were not associated with lung cancer risk; HRs (95% CI) for highest compared with lowest quartile were 1.08 (0.91–1.29) for total dietary folate, 1.00 (0.84–1.19) for food folate, and 1.09 (0.91–1.30) for food folic acid, respectively. Similarly, no associations were observed after stratifying by sex, race and smoking status, except for a positive association with total dietary folate intake among black women (HR 1.46, 95% CI 1.04–2.05 for the highest quartile compared with the lowest quartile, P trend = 0.02). Neither the use of folic acid-containing supplements nor food intake of vitamin B6, vitamin B12 and riboflavin were associated with lung cancer risk. Conclusions: Our findings do not support a protective effect of folate or folic acid for lung cancer prevention in a low-income population of black and white adults in the Southeastern US. Our finding of a positive association with total dietary folate intake among black women needs to be interpreted with caution and replicated in other studies. [ABSTRACT FROM AUTHOR]

Background: Most previous studies evaluating the association between leisure-time physical activity (LTPA) and risk of death were conducted among generally healthy individuals of European ancestry. We investigated the association of LTPA with all-cause and cause-specific mortality among East Asian populations, including healthy individuals and those with existing chronic diseases, which has been less well characterized.Methods: We performed pooled analyses among 467 729 East Asian individuals recruited in nine prospective cohorts included in the Asia Cohort Consortium. Cox proportional hazards regressions were used to derive hazard ratios (HRs) and 95% confidence intervals (CIs) associated with LTPA after adjusting for age, sex, education and marital and smoking status.Results: During a mean follow-up period of 13.6 years, 65 858 deaths were identified. Compared with those who reported no or less than 1 h of LTPA per week, an inverse association was observed between the amount of LTPA and all-cause and cause-specific mortality (P for trend < 0.001). The strength of the inverse association was stronger for death due to cardiovascular diseases and causes other than cancer deaths. An inverse association of LTPA with total mortality was observed among individuals with a severe and often life-threatening disease: cancer, stroke or coronary heart disease [hazard ratio (HR) = 0.81, 95% CI = 0.73-0.89 for high vs low LTPA) and those with other chronic diseases such as diabetes or hypertension (HR = 0.86, 95% CI = 0.80-0.93 for high vs low LTPA). No clear modifying effects by sex, body mass index or smoking status were identified.Conclusions: Regular participation in LTPA is associated with reduced mortality in middle-aged and elder Asians regardless pre-existing health conditions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential influence of dietary Se intake on mortality among Chinese populations.Design: We prospectively evaluated all-cause, CVD and cancer mortality risks associated with dietary Se intake in participants of the Shanghai Women's Health Study (SWHS) and the Shanghai Men's Health study (SMHS). Dietary Se intake was assessed by validated FFQ during in-person interviews. Cox proportional hazards models were used to calculate hazard ratios (HR) and 95 % CI.Setting: Urban city in China.Subjects: Chinese adults (n 133 957).Results: During an average follow-up of 13·90 years in the SWHS and 8·37 years in the SMHS, 5749 women and 4217 men died. The mean estimated dietary Se intake was 45·48 μg/d for women and 51·34 μg/d for men, respectively. Dietary Se intake was inversely associated with all-cause mortality and CVD mortality in both women and men, with respective HR for the highest compared with the lowest quintile being 0·79 (95 % CI 0·71, 0·88; P trend<0·0001) and 0·80 (95 % CI 0·66, 0·98; P trend=0·0268) for women, and 0·79 (95 % CI 0·70, 0·89; P trend=0·0001) and 0·66 (95 % CI 0·54, 0·82; P trend=0·0002) for men. No significant associations were observed for cancer mortality in both women and men. Results were similar in subgroup and sensitivity analyses.Conclusions: Dietary Se intake was inversely associated with all-cause and cardiovascular mortality in both sexes, but not cancer mortality. [ABSTRACT FROM AUTHOR]

Background: Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers.Methods and Findings: A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate.Conclusions: Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers. [ABSTRACT FROM AUTHOR]

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 <25) than over-weight (BMI ≥25) individuals. Positive associations with mortality were observed in subgroups defined by follow-up duration, comorbidity, age, smoking, and physical activity. Greater central adiposity is associated with increased mortality in Chinese adults, even among individuals with low BMI. Physicians and the public should be aware of central adiposity’s independent effects on health. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of uric acid (UA) levels with a panel of markers of oxidative stress and inflammation. Methods: Plasma UA levels, along with a panel of oxidative stress and inflammatory markers, were measured in 755 Chinese women. Results: Plasma UA levels were inversely associated with urinary levels of the oxidative stress marker F2-isoprostanes and positively correlated to levels of inflammatory markers, such as C-reactive protein and some proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) in blood as well as prostaglandin E2metabolites in urine. Conclusions: Plasma UA levels correlate to oxidation and inflammation biomarkers in opposite directions in women. [ABSTRACT FROM AUTHOR]

Background: Leisure time exercise has been linked to lower circulating levels of inflammatory markers. Few studies have examined the association of nonexercise physical activity with markers of inflammation and oxidative stress. Methods: This cross-sectional analysis included 1005 Chinese women aged 40-70 years. Usual physical activity was assessed through in-person interviews using a validated physical activity questionnaire. Plasma proinflammatory cytokines and urinary F2-isoprostanes were measured. Multivariable linear models were used to evaluate the association of inflammatory and oxidative stress markers with nonexercise physical activity and its major components. Results: Nonexercise physical activity accounted for 93.8% of overall physical activity energy expenditure. Levels of nonexercise physical activity were inversely associated with circulating concentrations of interleukin (IL)-6 ( Ptrend=0.004), IL-1β ( Ptrend=0.03) and tumor necrosis factor-alpha (TNF-α) ( Ptrend=0.01). Multivariable-adjusted concentrations of these cytokines were 28.2% for IL-6, 22.1% for IL-1β, and 15.9% for TNF-α lower in the highest quartile of nonexercise physical activity compared with the lowest quartile. Similar inverse associations were found for two major components of nonexercise physical activity, walking and biking for transportation, and household activity. No significant associations were observed between nonexercise physical activity and oxidative stress markers. Conclusion: Daily nonexercise physical activity is associated with lower levels of systemic inflammation. This finding may have important public health implications because this type of activity is the main contributor to overall physical activity among middle-aged and elderly women. [ABSTRACT FROM AUTHOR]

The potential long-term association between carbohydrate intake and the risk of coronary heart disease (CHD) remains unclear, especially among populations who habitually have high-carbohydrate diets. We prospectively examined intakes of carbohydrates and staple grains as well as glycemic index and glycemic load in relation to CHD among 117,366 Chinese women and men (40–74 years of age) without history of diabetes, CHD, stroke, or cancer at baseline in Shanghai, China. Diet was assessed using validated food frequency questionnaires. Incident CHD cases were ascertained during follow-ups (in women, the mean was 9.8 years and in men, the mean was 5.4 years) and confirmed by medical records. Carbohydrate intake accounted for 67.5% of the total energy intake in women and 68.5% in men. Seventy percent of total carbohydrates came from white rice and 17% were from refined wheat products. Positive associations between carbohydrate intakess and CHD were found in both sexes (all P for heterogeneity > 0.35). The combined multivariate-adjusted hazard ratios for the lowest to highest quartiles of carbohydrate intake, respectively, were 1.00, 1.38, 2.03, and 2.88 (95% confidence interval: 1.44, 5.78; P for trend = 0.001). The combined hazard ratios comparing the highest quartile with the lowest were 1.80 (95% confidence interval: 1.01, 3.17) for refined grains and 1.87 (95% confidence interval: 1.00, 3.53) for glycemic load (both P for trend = 0.03). High carbohydrate intake, mainly from refined grains, is associated with increased CHD risk in Chinese adults. [ABSTRACT FROM PUBLISHER]

Background: 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. Methods: 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. Results: 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 <0.0001, respectively). Regular participation in exercise or sports reduced T2DM risk (HR = 0.86, 95%CI: 0.76–0.98). Moderate alcohol intake (1–3 drinks/day) was inversely related to T2DM risk (HR = 0.80, 95%CI: 0.67–0.94). Cigarette smoking, on the other hand, was associated with increased T2DM risk; HRs were 1.25 (95%CI: 1.00–1.56) for smoking more than 20 cigarettes per day and 1.28 (95%CI: 1.04–1.57) for smoking more than 40 pack-years. Conclusions: Physical activity and moderate alcohol intake are inversely associated with T2DM risk, whereas smoking was positively associated with T2DM risk among middle-age and elderly Chinese men. Preventive measures should be developed to focus on these modifiable lifestyle habits to reduce the upward trend of T2DM. [ABSTRACT FROM AUTHOR]

Abstract: Background: The hypertriglyceridemic waist phenotype (defined using both elevated waist circumference and triglycerides) and visceral adiposity index (VAI, defined using waist circumference, body mass index, triglycerides, and high-density lipoprotein cholesterol) have been suggested to be inexpensive yet effective markers of visceral (intra-abdominal) obesity and related dysmetabolic state. These markers may be particularly useful to Asian populations who generally have a low body weight but are prone to visceral adiposity. Methods: We examined associations of the hypertriglyceridemic waist phenotype and VAI with risk of coronary heart disease (CHD) in a nested case-control study conducted within two prospective cohort studies of Chinese adults. We identified 355 incident cases of CHD and 697controls matched for sex, age, and date and time of baseline sample collection. Anthropometric and lipid measurements were performed and used to define the hypertriglyceridemic waist phenotype and VAI according to published methods. Conditional logistic regression was used to evaluate the associations. Results: Cases had a higher prevalence of the hypertriglyceridemic waist phenotype and higher VAI score than controls in both sexes. Adjusted odds ratios of CHD associated with hypertriglyceridemic waist were 5.18 (95% CI, 2.46–10.9) and 4.63 (2.03–10.5) for women and men, respectively. Adjusted odds ratios of CHD comparing the highest vs. lowest quartile of VAI were 4.44 (95% CI, 2.24–8.82) and 4.23 (1.99–9.00) for women and men, respectively. Conclusion: Our study demonstrates, for the first time, that the hypertriglyceridemic waist phenotype and high VAI score are associated with substantially elevated risk of CHD in Chinese men and women. [Copyright &y& Elsevier]

OBJECTIVES: This study evaluated associations of various anthropometric measures of adiposity with a panel of inflammatory and oxidative stress markers in a relatively lean population of Chinese women. METHODS: This analysis included 1,005 Chinese women aged 40-70 years. Plasma concentrations of inflammatory and oxidative stress markers were measured. Anthropometric measurements were taken by trained interviewers. RESULTS: Body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) were all positively and linearly associated with the inflammatory markers, CRP, TNF-α, soluble TNF-receptor 1 (sTNF-R1), and IL-6. A significant positive association of these measures of adiposity with the oxidative stress marker F_2-IsoP-M, a metabolite of F_2-IsoPs, but with not F_2-IsoPs was found. Differences in biomarkers between extreme quartiles of anthropometric measurements varied widely, ranging from 9.7% for sTNF-R1 to 162.0% for CRP. For each specific biomarker, various anthropometric measurements exhibited similar ability to explain variations in the biomarker, with the biggest partial r^{2} (11%) observed for CRP. CONCLUSIONS: This study suggests that both general adiposity (measured by BMI) and central adiposity (measured by WC and WHtR) are positively and similarly associated with various markers of inflammation and oxidative stress in relatively lean Chinese women. The metabolite F_2-IsoP-M of F_2-IsoPs may be a better marker of in vivo oxidative stress than its parent compounds. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The authors prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and performed a meta-analysis of published data. Included in the analysis were 71,550 women recruited into the Shanghai Women's Health Study (Shanghai, China) in 1997–2000. Usual soy food intake was assessed at baseline and reassessed during follow-up through in-person interviews. During a mean follow-up period of 9.1 years, 370 incident lung cancer cases were identified; 340 patients were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer (Ptrend = 0.004); the hazard ratio for the highest quintile of intake compared with the lowest was 0.63 (95% confidence interval: 0.44, 0.90). This inverse association appeared predominately among women with later age at menopause (Pinteraction = 0.01) and for aggressive lung cancer as defined by length of survival (<12 months vs. ≥12 months; Pheterogeneity = 0.057). Meta-analysis of 7 studies conducted among nonsmokers found a summary relative risk of 0.59 (95% confidence interval: 0.49, 0.71) for the highest categories of soy or isoflavone intake versus the lowest. This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive tumors, and its effect may be modified by endogenous estrogens. [ABSTRACT FROM PUBLISHER]

Correspondence to: Xiao-Ou Shu, MD, PhD, Vanderbilt Epidemiology Center, 2525 West End Ave, Ste 600 (IMPH), Nashville, TN 37203-1738 (e-mail: xiao-ou.shu@vanderbilt.edu) and Yong-Bing Xiang, MD, MSc, Shanghai Cancer Institute, No. 25, Lane 2200, Xie Tu Road, Shanghai 200032, People’s Republic of China (e-mail: ybxiang@shsci.org).Background Epidemiologic studies on the relationship between vitamin intake and liver cancer risk are sparse and inconsistent. Methods We evaluated vitamin intake from diet and supplements and risk of liver cancer in 132 837 women and men from China who were recruited into the Shanghai Women’s Health Study from 1997 to 2000 or the Shanghai Men’s Health Study from 2002 to 2006. In-person interviews, using a validated food-frequency questionnaire, were conducted to collect data on dietary habits. Follow-up consisted of in-person surveys and record linkage. Hazard ratios and 95% confidence intervals were estimated using Cox proportional hazard models with adjustment for potential confounders to compare liver cancer risk among participants with high vs low vitamin intake. All statistical tests were two-sided. Results After excluding the first 2 years of follow-up, 267 participants (including 118 women and 149 men) developed liver cancer during an average of 10.9 (Shanghai Women’s Health Study) or 5.5 (Shanghai Men’s Health Study) years of follow-up. Dietary vitamin E intake was inversely associated with liver cancer risk (Ptrend = .01), as was vitamin E supplement use (hazard ratio = 0.52, 95% confidence interval = 0.30 to 0.90). This association was consistent among participants with and without self-reported liver disease or a family history of liver cancer. Vitamin C and multivitamin use was associated with increased risk among participants with self-reported liver disease or family history of liver cancer, whereas intake of vitamin C and other vitamins from dietary sources was unrelated to liver cancer risk. Conclusions Vitamin E intake, either from diet or supplements, may reduce the risk of liver cancer. [ABSTRACT FROM PUBLISHER]

The effects of diet on breast cancer are controversial and whether the effects vary with hormone receptor status has not been well investigated. This study evaluated the associations of dietary factors with risk for breast cancer overall and by the hormone receptor status of tumors among Chinese women. The Shanghai Breast Cancer Study, a large, population-based, case-control study, enrolled 3,443 cases and 3,474 controls in 1996–1998 (phase I) and 2002–2005 (phase II); 2676 cases had estrogen receptor (ER) and progesterone receptor (PR) data. Dietary intake was assessed using a validated, quantitative, food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were derived from multivariate, polychotomous, unconditional logistic regression models. Total vegetable intake was inversely related to breast cancer risk, with an adjusted OR for the highest quintile of 0.80 (95% CI = 0.67–0.95; P trend = 0.02). Reduced risk was also related to high intake of allium vegetables (P trend = 0.01) and fresh legumes (P trend = 0.0008). High intake of citrus fruits and rosaceae fruits were inversely associated with breast cancer risk (P trend = 0.003 and 0.004, respectively), although no consistent association was seen for total fruit intake. Elevated risk was observed for all types of meat and fish intake (all P trend < 0.05), whereas intakes of eggs and milk were associated with a decreased risk of breast cancer (both P trend <0.05). There was little evidence that associations with dietary intakes varied across the 4 tumor subtypes or between ER+/PR+ and ER-/PR- tumors (P for heterogeneity >0.05). Our results suggest that high intake of total vegetables, certain fruits, milk, and eggs may reduce the risk of breast cancer, whereas high consumption of animal-source foods may increase risk. The dietary associations did not appear to vary by ER/PR status. [ABSTRACT FROM PUBLISHER]

Aims: 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. Materials and Methods: 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. Results: 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. Conclusions: Our study suggests that markers of an early age at peak height velocity, i.e. early menarche age and low leglength- to-sitting height ratio, may be associated with diabetes risk later in life and this association is likely to be mediated through obesity. [ABSTRACT FROM AUTHOR]

Etiologic differences between subtypes of breast cancer defined by estrogen receptor (ER) and progesterone receptor (PR) status are not well understood. The authors evaluated associations of hormone-related factors with breast cancer subtypes in a population-based case-control study involving 1,409 ER-positive (ER+)/PR-positive (PR+) cases, 712 ER-negative (ER−)/PR-negative (PR−) cases, 301 ER+/PR− cases, 254 ER−/PR+ cases, and 3,474 controls aged 20–70 years in Shanghai, China (phase I, 1996–1998; phase II, 2002–2005). Polytomous logistic regression and Wald tests for heterogeneity across subtypes were conducted. Breast cancer risks associated with age at menarche, age at menopause, breastfeeding, age at first livebirth, waist-to-hip ratio, and oral contraceptive use did not differ by hormone receptor status. Among postmenopausal women, higher parity (≥2 children vs. 1) was associated with reduced risk (odds ratio (OR) = 0.69, 95% confidence interval (CI): 0.52, 0.91) and higher body mass index (BMI; weight (kg)/height (m)2) with increased risk (highest quartile: OR = 2.40, 95% CI: 1.65, 3.47) of the ER+/PR+ subtype but was unrelated to the ER−/PR− subtype (for parity, Pheterogeneity = 0.02; for BMI, Pheterogeneity < 0.01). Hormone replacement therapy (OR = 2.25, 95% CI: 1.40, 3.62) and alcohol consumption (OR = 1.59, 95% CI: 1.01, 2.51) appeared to be preferentially associated with the ER+/PR− subtype. These findings indicate that BMI, parity, hormone replacement therapy, and alcohol consumption may play different roles in subtypes of breast cancer. More research is needed to better understand the etiology of 2 relatively rare subtypes, ER+/PR− tumors and ER−/PR+ tumors. [ABSTRACT FROM PUBLISHER]

Methionine, folate, vitamin B6, vitamin B12, niacin, and riboflavin intakes may be related to breast carcinogenesis. These associations may vary by breast cancer type. Using the prospective cohort Shanghai Women's Health Study (1997–2008) including 718 Chinese breast cancer cases, the authors evaluated baseline dietary intake of these factors and breast cancer risk and whether the associations varied by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) status. They estimated associations using hazard ratios and 95% confidence intervals from Cox proportional hazards regression models and stratified analyses by menopausal status and ER/PR status. Lowest quantile of intake was used as the comparison group. For postmenopausal women, dietary intakes of methionine and B vitamins were not associated with breast cancer risk. For premenopausal women, higher intake of folate was associated with decreased breast cancer risk (hazard ratio = 0.58, 95% confidence interval: 0.34, 0.99 for the highest vs. lowest quintile of intake). Only niacin intake was associated with ER+/PR+ breast cancer risk (hazard ratio = 1.62, 95% confidence interval: 1.07, 2.46; P for trend = 0.04 for the highest vs. lowest quartile of intake). Findings support the hypothesis that high folate intake may reduce breast cancer risk and that the association may vary by menopausal and ER/PR status. [ABSTRACT FROM PUBLISHER]

The fibroblast growth factor receptor 2 gene (FGFR2) has been associated with the risk of breast cancer in multiple ethnic populations, and its effect has been suggested to be hormone-dependent. A large, 2-stage, population-based case-control study was conducted in urban Shanghai, China, during the periods of 1996–1998 and 2002–2005. Exposure and genotyping information from 2,073 patients with breast cancer and 2,084 age-matched population controls was available for evaluation of the interactions between FGFR2 polymorphisms and exogenous estrogen exposure in the development of breast cancer. A logistic regression model was used to compute adjusted odds ratios and 95% confidence intervals. Of 20 genotyped and 25 imputed single nucleotide polymorphisms (SNPs), 22 were significantly associated with breast cancer. Three genotyped SNPs in close linkage disequilibrium, rs2303568, rs3135730, and rs1078806, and an imputed SNP of rs755793 in complete linkage disequilibrium with other 8 SNPs were observed to interact significantly with oral contraceptive (OC) use. The SNP-cancer association was evident only among OC users, and the OC use was only associated with the risk of breast cancer among carriers of these minor alleles at these loci. These findings suggest that genetic variants in FGFR2 may modify the role of OC use in causing breast cancer in Chinese women. [ABSTRACT FROM PUBLISHER]

Background: Studies have found that tea polyphenols inhibit aromatase. Because of the substantial difference in levels of estrogens between premenopausal and postmenopausal women, the relationship between tea consumption and breast cancer risk may depend on menopausal status. Methods: We examined this hypothesis in the Shanghai Women''s Health Study, a population-based cohort study of 74,942 Chinese women. Results: We found a time-dependent interaction between green tea consumption and age of breast cancer onset (p for interaction, 0.03). In comparison with non-tea drinkers, women who started tea-drinking at 25 years of age or younger had a hazard ratio (HR) of 0.69 (95% confidence interval [CI]: 0.41–1.17) to develop premenopausal breast cancer. On the other hand, compared with non-tea drinkers, women who started tea drinking at 25 years of age or younger had an increased risk of postmenopausal breast cancer with an HR of 1.61 (95% CI: 1.18–2.20). Additional analyses suggest regularly drinking green tea may delay the onset of breast cancer. Conclusions: Further studies are needed to confirm our findings. [Copyright &y& Elsevier]

Purpose: Gallstone disease is more common among overweight individuals, particularly in women. We conducted a cross-sectional case-control study of Chinese women nested in the Shanghai Women''s Health Study (SWHS) to evaluate the association of gallstone disease with body mass index (BMI), waist to hip ratio (WHR), and physical activity (PA). Methods: The study included 8,485 women with self-reported, physician-diagnosed, prevalent gallstone disease and 16,970 frequency-matched controls by birth year and age at gallstone diagnosis (4-year intervals). Information on height, weight history, waist and hip circumferences, physical activities, and other exposures was obtained by in-person interview. Results: : Usual BMI (p trend < 0.001) and WHR (p trend < 0.001) were both related to a high prevalence of gallstone disease, and a significant interaction between BMI and WHR on gallstone risk was found (odds ratio [OR] = 3.82, 95%CI [95% confidence interval] 2.47–5.23 for those with both highest BMI and WHR relative to those with lowest BMI and WHR, p interaction = 0.03). Gallstone risk was positively associated with cumulative occupational sitting time (p trend = 0.01) and inversely associated with occupational cumulative energy expenditure (p trend = 0.03) as well as with household PA (p trend = 0.02). Conclusions: Our findings further support that overall and central excessive adiposity is an independent risk factor for gallstones in women. In addition, regardless of adiposity level, being physically active may ameliorate the risk of this disease. [Copyright &y& Elsevier]

To assess the association between paternal military service and risk for childhood leukemia, the authors analyzed data from three case-control studies conducted by the Children's Cancer Group from 1983 to 1993. A total of 605 acute myeloid leukemia (AML, age ≪ 18 years) cases, 2,117 acute lymphoblastic leukemia (ALL, age ≪ 14 years) cases, and 3,155 individually matched controls were included in these studies. Paternal military history and other exposure data were obtained in 2,343 matched case-control sets, including 1,805 ALL and 528 AML cases. Paternal general military service was not associated with the leukemia risk. A small, but significant, increase in the risk for AML was seen, however, among offspring of veterans who had served in Vietnam or Cambodia (odds ratio (OR) = 1.7; 95% confidence interval (Cl): 1.0, 2.9), after adjustment for paternal education, race, income, smoking, X-ray exposure, and marijuana use. The risk was predominantly present in children diagnosed before the age of 2 (OR = 4.6; 95% Cl: 1.3, 16.1), although there were inconsistencies in the risks associated with length of time served and interval between service and diagnosis of leukemia. Military service in Vietnam or Cambodia was unrelated to the risk for ALL. The etiologic importance, if any, of these observations has yet to be determined. Am J Epidemiol 2000;151:231 —40. [ABSTRACT FROM PUBLISHER]

Circulating estrogen levels have been related to the risk of several female cancers. Blood levels of estrogen are controlled by estrogen synthesis enzymes. Genetic variation of estrogen genes thus may influence circulating estrogen levels. We investigated the associations of genetic polymorphisms in CYP19A1, a critical gene involved in estrogen synthesis, with plasma levels of sex hormones among postmenopausal Chinese women.Included in this study were 345 postmenopausal community controls from a population-based case-control study conducted in Shanghai. Fasting blood samples from those women were measured for blood estradiol, estrone, estrone sulfate, and testosterone. A total of 19 genetic polymorphisms in CYP19A1 were genotyped using ABI7900 or PCR-restriction fragment length polymorphism methods. Differences in plasma levels of hormones by genotype were examined using variance analysis.The geometric means of plasma levels of estradiol, estrone, estrone sulfate, and testosterone were 10.1, 16.8, 969.0, and 202.9 pg/ml, respectively, for this study population. We found that plasma levels of estrone were associated with rs28566535 (P=0.0180), rs730154 (P=0.0141), and rs936306 (P=0.0274) in block 2. In the same block, the haplotype CGCTA was related to level of estrone (P=0.0064). Single nucleotide polymorphism rs1902584 in block 1 was associated with estradiol only in overweight postmenopausal women. No clear association with sex hormones was noted for the other genetic polymorphisms evaluated in the study.Single nucleotide polymorphisms in blocks 1 and 2 of the CYP19A1 gene are related to plasma levels of estrogen among postmenopausal Chinese women and may therefore play an important role in the etiology of hormone-related cancers. [ABSTRACT FROM AUTHOR]

Abstract: The Cytochrome P450 1B1 (CYP1B1) is one of the major CYP450 enzymes catalyzing 4-hydroxylation, an important elimination step for estrogens. Relatively little is known, however, about the impact of this gene on the onset and cessation of menstruation, which are the significant milestones in a woman''s life and predictors of many hormone related diseases. In this report, we described the association of four SNPs in the CYP1B1 gene, Arg48Gly, Ala119Ser, Leu432Val, and Asp449Asp, with the ages of menarche and menopause, years of menstruation and total number of menstrual cycles. Included in the study were 1958 community controls from two recently completed population-based case-control studies of breast cancer and endometrial cancer. No association was observed between the CYP1B1 polymorphisms and the age of menarche among either pre- or post-menopausal women. Among the women who experienced natural menopause, the three non-synonymous SNPs were significantly associated with menopausal age, years of menstruation, and total number of menstrual cycles. The Gly and Ser alleles of Arg48Gly and Ala119Ser were associated with later menopause, more years of menstruation and more menstrual cycles, while women with allele Val at Leu432Val had a 0.9 year earlier menopause, 1.0 year shorter reproductive span, and 12.6 fewer menstrual cycles than those women without this allele. In conclusion, the results from this study suggested that CYP1B1 genetic polymorphisms may be associated with the natural onset of menopause. [Copyright &y& Elsevier]

Abstract: Previous studies have found that estrogen enhances the effect of insulin-like growth factor-I (IGF-I) levels on breast cancer cell growth. Participants in the Shanghai Breast Cancer Study (SBCS) consumed large amounts of soy that was high in isoflavones, which act as weak estrogens and as anti-estrogens. We assessed whether soy protein intake modified the effect of IGF-I levels on breast cancer risk. The SBCS is a population-based case-control study of breast cancer among women aged 25-64 conducted between 1996 and 1998 in urban Shanghai. In-person interviews were completed with 1,459 incident breast cancer cases ascertained through a population-based cancer registry and 1,556 controls randomly selected from the general population (with respective response rates of 91% and 90%). This analysis is restricted to the 397 cases and 397 matched controls for whom information on IGF-I levels was available. For premenopausal breast cancer, we found nearly significant interactions between soy protein intake and IGF-I levels (P = 0.080) and insulin-like growth factor-binding protein-3 (IGFBP-3) levels (P = 0.057). The direction of the interaction appeared to be negative for IGF-I levels but was positive for IGFBP-3 levels. No interaction was evident between soy protein intake and IGF-I or IGFBP-3 levels among postmenopausal women. Our results suggest that soy protein intake may negatively modulate the effect of IGF-I and may positively modulate the effect of IGFBP-3 levels on premenopausal breast cancer risk. Further studies are needed to confirm our finding and to understand the biological mechanisms of these potential interactions. [ABSTRACT FROM AUTHOR]

Oral contraceptive (OC) use has been associated with alterations in carbohydrate metabolism. We examined the effect of OC use on the risk of diabetes among Chinese women. A nested case-control study was conducted among 57,130 women screened for diabetes at enrollment for the Shanghai Women''s Health Study, a population-based cohort study of Chinese women aged 40–70 years in Shanghai, China. Included in this study were 259 women newly diagnosed with diabetes and 2072 age-matched controls (8 controls per case), randomly selected from women who tested negative for urine glucose. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) were used to measure the strength of the association between OC use and diabetes risk. Overall, OC use was not associated with the risk of diabetes. Stratified analysis by menopausal status revealed a dose–response relationship between the duration of OC use and the risk of diabetes among premenopausal women (p for trend = 0.02), with a 3.2-fold elevated risk observed among those who used OC longer than 1 year. Risk of diabetes diminished with increasing time since last OC use (p = 0.02). Use of intrauterine devices was associated with a reduced risk of diabetes in both pre- and postmenopausal women (OR = 0.67, CI: 0.48–0.93). These findings suggest that recent use (within 5 years) and continued use (>1 year) of OCs may increase the risk of diabetes among Chinese women. However, the attributable risk for diabetes among OC users in the general population, if confirmed by further studies, appears to be small. [Copyright &y& Elsevier]

Background: Alterations of the HER2 (also known as erbB-2 or neu) proto-oncogene have been implicated in the carcinogenesis and prognosis of breast cancer. A polymorphism at codon 655 (GTC/valine to ATC /isoleucine [Val(655)Ile]) in the transmembrane domain-coding region of this gene has been identified and may be associated with the risk of breast cancer. We evaluated this hypothesis in a subgroup of women who participated in a large-scale, population-based, case-control study of breast cancer in Shanghai, China.Methods: Genomic DNA from 339 patients with breast cancer and 361 healthy control subjects was examined for the Val(655)Ile polymorphism with a polymerase chain reaction-restriction fragment-length polymorphism-based assay. All study subjects completed a structured questionnaire during an in-person interview. All P values are from two-sided tests.Results: We found that 25.1% of the case patients and 21.7% of the control subjects were heterozygous for the Val allele and 3.2% of the case patients and 0. 3% of the control subjects were homozygous for this allele (P =.005). Compared with women with the Ile/Ile genotype, women who had the Ile/Val or Val/Val genotype had an elevated risk of breast cancer (odds ratio [OR] = 1.4; 95% confidence interval [CI] = 1.0-2.0; P =. 05) after adjustment for age, educational level, study period, history of breast fibroadenoma, leisure physical activity, and age at first live birth. The risk was elevated even more among women who were homozygous for the Val allele (OR = 14.1; 95% CI = 1.8-113.4). The association was more pronounced among younger women (45 years). The adjusted OR associated with the Val allele was 1.7 (95% CI = 1.1-2.6) for younger women and 1.0 (95% CI = 0.5-1.9) for older women.Conclusions: Results of this study suggest that polymorphisms of the HER2 gene may be important susceptibility biomarkers for breast cancer risk, particularly among younger women. [ABSTRACT FROM AUTHOR]

Background: Little research has focused on the relationship between gut microbiome and chemotherapy‐induced toxicity. Methods: This prospective study involves 301 patients with breast cancer who had prechemotherapy stool samples collected. Gut microbiome was sequenced by shotgun metagenomics; associations with chemotherapy‐induced toxicities during first‐line treatment by gut microbial diversity, composition, and metabolic pathways with severe (i.e., grade ≥3) hematological and gastrointestinal toxicities were evaluated via multivariable logistic regression. Results: High prechemotherapy α‐diversity was associated with a significantly reduced risk of both severe hematological toxicity (odds ratio [OR] = 0.94; 95% CI, 0.89–0.99; p =.048) and neutropenia (OR = 0.94; 95% CI, 0.89–0.99; p =.016). A high abundance of phylum Synergistota, class Synergistia, and order Synergistales were significantly associated with a reduced risk of severe neutropenia; conversely, enrichment of phylum Firmicutes C, class Negativicutes, phylum Firmicutes I, and class Bacilli A, order Paenibacillales were significantly associated with an increased risk of severe neutropenia (p range: 0.012–2.32 × 10–3; false discovery rate <0.1). Significant positive associations were also observed between severe nausea/vomiting and high Chao1 indexes, β‐diversity (p <.05), 20 species belonging to the family Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae (p value range: 6.14 × 10–3 to 1.33 × 10–5; false discovery rate <0.1), and three metabolic pathways involved in reductive tricarboxylic acid cycle I and cycle II, and an incomplete reductive tricarboxylic acid cycle (p <.01). Conversely, a high abundance of species Odoribacter laneus and the pathway related to the L‐proline biosynthesis II were inversely associated with severe nausea/vomiting. Conclusions: Our study suggests that gut microbiota may be a potential preventive target to reduce chemotherapy‐induced toxicity. The gut microbiome has been shown to affect chemotherapy efficacy, but its association with chemotherapy‐induced toxicity has been little investigated. Prechemotherapy gut microbiome diversity and abundance of certain bacteria were associated with chemotherapy‐induced toxicities, suggesting that gut microbiome manipulation could be a potential target for reducing chemotherapy‐induced toxicity. [ABSTRACT FROM AUTHOR]

Background: We characterized age at diagnosis and estimated sex differences for lung cancer and its histological subtypes among individuals who never smoke. Methods: We analyzed the distribution of age at lung cancer diagnosis in 33,793 individuals across 8 cohort studies and two national registries from East Asia, the United States (US) and the United Kingdom (UK). Student's t-tests were used to assess the study population differences (Δ years) in age at diagnosis comparing females and males who never smoke across subgroups defined by race/ethnicity, geographic location, and histological subtypes. Results: We found that among Chinese individuals diagnosed with lung cancer who never smoke, females were diagnosed with lung cancer younger than males in the Taiwan Cancer Registry (n = 29,832) (Δ years = −2.2 (95% confidence interval (CI):−2.5, −1.9), in Shanghai (n = 1049) (Δ years = −1.6 (95% CI:-2.9, −0.3), and in Sutter Health and Kaiser Permanente Hawaiʽi in the US (n = 82) (Δ years = −11.3 (95% CI: −17.7, −4.9). While there was a suggestion of similar patterns in African American and non-Hispanic White individuals. the estimated differences were not consistent across studies and were not statistically significant. Conclusions: We found evidence of sex differences for age at lung cancer diagnosis among individuals who never smoke. [ABSTRACT FROM AUTHOR]

Presents information on a study on the association between breastfeeding and the reduced risk of the development of acute childhood leukemia. Materials and methods; Results; Conclusions.

Details a population-based case-control study of role of paternal smoking in the etiology of childhood cancer among offspring of nonsmoking mothers in Shanghai, China. Use of odd ratios to measure the association between paternal smoking and risk of childhood cancers; Increase in risks with the increase in pack-years of paternal preconception smoking.

Discusses a study on whether or not parental drinking and smoking during pregnancy are linked with an increase risk of cancer in offspring by Xiao-Ou Shu and other scientists. Content of cigarette smoke; Research methodology; Results of research; Discussion of results.

Introduction: Theoretically, some metabolic traits may predispose older individuals to weight loss during aging, leading to increased all-cause mortality and many serious health issues. Biomarkers to robustly predict progressive weight loss during aging are, however, lacking. We prospectively assessed if urinary levels of F2-isoprostanes and their peroxisomal β-oxidation metabolite, 2,3-dinor-5,6-dihydro-15-F2t-isoprostane (F2-IsoP-M), were associated with subsequent weight loss in middle-aged and older women. Methods: Included in the analysis were 2,066 women aged 40–70 years, a subset of a prospective cohort study. F2-isoprostanes (F2-IsoPs) and its β-oxidation metabolite, F2-IsoP-M, were measured in urine using gas chromatography-mass spectrometry. Measurements of anthropometry and exposures to major determinants of body weight were performed at baseline and repeated thrice over 15-year follow-up. The longitudinal associations of F2-IsoP-M and the F2-IsoP-M to its parent compound, F2-IsoP, ratio (MPR) with repeatedly measured weight changes were examined using linear mixed-effect models. Results: After adjusting for time-varying covariates: energy intake, physical activity, and comorbidity index, among others, levels of F2-IsoP-M and the MPR were both inversely associated with percentage of weight change. Weight in the highest quartile of these two biomarkers was 1.33% (95% CI = −2.41, −0.24) and 1.09% (95% CI = −2.16, −0.02) lower than those in the lowest quartile group, with p for trend of 0.01 and 0.03, respectively. The inverse association was consistently seen across follow-up periods, although appearing stronger with prolonged follow-up. There was no association between the parent compound, F2-IsoPs, and weight change. Conclusion: This study demonstrates the first piece of evidence to associate F2-IsoP metabolism, peroxisomal β-oxidation, with weight loss in older women. Further investigations into the role of lipid peroxidation and peroxisomal β-oxidation in weight change among older individuals are warranted. [ABSTRACT FROM AUTHOR]

Background: Little is known about the time course of mortality reduction following smoking cessation in Asians who have smoking behaviours distinct from their Western counterparts. We evaluated the level of reduction in all-cause, cardiovascular disease (CVD) and lung cancer mortality by years since quitting smoking, in Asia.Methods: Using Cox regression, we analysed individual participant data (n = 709 151) from 16 prospective cohorts conducted in China, Japan, Korea/Singapore, and India/Bangladesh, separately by cohorts. Cohort-specific hazard ratios (HRs) were combined using a random-effects meta-analysis.Results: During a mean follow-up of 12.0 years, 108 287 deaths were ascertained-35 658 from CVD and 7546 from lung cancer. Among Asian men, a dose-response relationship of risk reduction in deaths from all causes, CVD and lung cancer was observed with an increase in years after smoking cessation. Compared with never smokers, however, all-cause and CVD mortality among former smokers remained elevated 10-14 years after quitting [multivariable-adjusted HR (95% confidence interval (CI) = 1.25 (1.13-1.37) and 1.20 (1.02-1.41), respectively]. Lung cancer mortality stayed almost 2-fold higher than among never smokers 15-19 years after smoking cessation [1.97 (1.41-2.73)], particularly among former heavy smokers [2.62 (1.71-4.00)]. Women who quitted for ≥5 years retained a significantly elevated mortality from all causes, CVD and lung cancer. Overall patterns of the cessation-mortality associations were similar across countries.Conclusions: Our findings suggest that adverse effects of tobacco smoking persist for an extended time period, even for more than two decades, which is beyond the time windows defined in current clinical guidelines for risk assessment of lung cancer and CVD. [ABSTRACT FROM AUTHOR]

Background: Robust and reliable prognosis prediction models have not been developed and validated for Asian patients with breast cancer, a rapidly growing yet understudied population in the United States.Methods: We used longitudinal data from the Shanghai Breast Cancer Survival Study, a population-based prospective cohort study (n = 5042), to develop prediction models for 5- and 10-year disease-free survival (DFS) and overall survival (OS). The initial models considered age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, and estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status. We then evaluated whether the addition of modifiable lifestyle factors (physical activity, soy isoflavones intake, and postdiagnostic weight change) improved the models. All final models have been validated internally and externally in the National Cancer Database when applicable.Results: Our final models included age at diagnosis, tumor grade, tumor size, number of positive nodes, TNM stage, chemotherapy, tamoxifen therapy, ER status, PR status, 6-month postdiagnostic weight change, interaction between ER status and tamoxifen therapy, and interaction between age and TNM stage. The internal validation yielded C-statistics of 0.76, 0.74, 0.78, and 0.75 for 5-year DFS, 10-year DFS, 5-year OS, and 10-year OS, respectively. The external validation yielded C-statistics of 5- and 10-year OS both at 0.78 for Chinese ethnicity, 0.79 for East Asian ethnicity, and 0.75 and 0.76 for all ethnic groups combined.Conclusion: We developed prediction models for breast cancer prognosis from a large prospective study. Our prognostic models performed very well in women from the United States-particularly in Asian American women-and demonstrated high prediction accuracy and generalizability. [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested that physical activity may modulate gut microbiome composition. We investigated associations of long-term regular exercise with gut microbiota among middle-aged and older urban Chinese individuals. Gut microbiota was assessed using 16S ribosomal ribonucleic acid gene sequencing of stool samples from 2,151 participants from the Shanghai Women's Health Study and Shanghai Men's Health Study. Participants were free of cancer, diabetes, and cardiovascular diseases at the time of stool sample collection. Physical activity was assessed in repeat surveys between 1996 and 2015 using validated questionnaires. Regular exercise was defined as any type of leisure-time physical activity with a standard metabolic equivalent score >3.0. Stool samples were collected using the 95% ethanol method between 2015 and 2018 with an average of 3.0 years (SD = 0.9) after the latest exposure assessment. General linear regression and permutational multivariate analysis of variance were carried out to evaluate associations of microbial α- and β-diversity with regular exercise participation. Logistic regression and linear regression models were used to evaluate the prevalence and relative abundance of individual taxa in association with regular exercise. Regular exercise was significantly associated with β-diversity (Bray–Curtis and Jaccard dissimilarities, both false discovery rates = 0.03%, 0.12% and 0.09% variance explained, respectively) but not with α-diversity. Relative abundance of genus Ruminococcus was significantly lower among regular exercisers compared with nonexercisers (median relative abundance: 0.64% vs. 0.81%, false discovery rate <0.10). Further studies are needed to validate the findings from this study and evaluate health benefits of regular exercise on gut microbiota. [ABSTRACT FROM AUTHOR]

Objective: American adults gain on average 1-2 lb/year. Sociodemographic and lifestyle factors have been shown to influence body weight. This influence has not yet been well characterized among blacks and low-income Americans, who are at high risk for obesity and related diseases. Methods: Included in the study were 12,261 blacks and 6,307 whites, 40-69 years old, who participate in the Southern Community Cohort Study, had no history of diabetes, cardiovascular disease, or cancer, and reported ≥2 body weight measures, one at baseline and another during follow-up. Mixed model was used to evaluate 5-year weight change in relation to baseline factors and changes in factors during follow-up. Analyses were conducted among all subjects and stratified by sex and race and baseline obesity status. Differences in 5-year weight change>1 lb with FDR-p<0.10 were considered significant. Results: During follow-up (median: 6 years; range: 0.5-15 years), participants gained 2.5 lb/year. After mutual adjustments, greater 5-year weight gain was seen among men (+1.61 lb) than women and associated with getting married (+1.67 lb), quitting smoking (+4.72 lb), and transition to menopause (+1.98 lb). The association for marital status change was most evident among white men (+5.80 lb) and the association for quitting smoking was most evident among subjects with baseline BMI>35 (+8.95 lb). Diet and other lifestyle factors (e.g., physical activity) overall contributed modestly to 5-year weight change in this population, although associations were observed for per serving increase in greens and beans among white women (-4.61 lb) and dairy among white men (+3.30 lb) and Healthy Eating Index among subjects with BMI>35 (-2.02 lb per 10 points increase). Conclusion: Changes in smoking, marriage, and menopause status contribute to body weight change among low-income Americans. Certain dietary factors are also related to weight change, but the association may vary by sex, race, and obesity status. Disclosure: J. Yang: None. X. Shu: None. D. Yu: None. [ABSTRACT FROM AUTHOR]

Background: Plasma proteins are potential biomarkers for complex diseases. We aimed to identify plasma protein biomarkers for lung cancer. Methods: We investigated genetically predicted plasma levels of 1130 proteins in association with lung cancer risk among 29,266 cases and 56,450 controls of European descent. For proteins significantly associated with lung cancer risk, we evaluated associations of genetically predicted expression of their coding genes with the risk of lung cancer. Results: Nine proteins were identified with genetically predicted plasma levels significantly associated with overall lung cancer risk at a false discovery rate (FDR) of <0.05. Proteins C2, MICA, AIF1, and CTSH were associated with increased lung cancer risk, while proteins SFTPB, HLA-DQA2, MICB, NRP1, and GMFG were associated with decreased lung cancer risk. Stratified analyses by histological types revealed the cross-subtype consistency of these nine associations and identified an additional protein, ICAM5, significantly associated with lung adenocarcinoma risk (FDR < 0.05). Coding genes of NRP1 and ICAM5 proteins are located at two loci that have never been reported by previous GWAS. Genetically predicted blood levels of genes C2, AIF1, and CTSH were associated with lung cancer risk, in directions consistent with those shown in protein-level analyses. Conclusion: Identification of novel plasma protein biomarkers provided new insights into the biology of lung cancer. [ABSTRACT FROM AUTHOR]

Background: DNA methylation plays a critical role in breast cancer development. Previous studies have identified DNA methylation marks in white blood cells as promising biomarkers for breast cancer. However, these studies were limited by low statistical power and potential biases. Using a new methodology, we investigated DNA methylation marks for their associations with breast cancer risk.Methods: Statistical models were built to predict levels of DNA methylation marks using genetic data and DNA methylation data from HumanMethylation450 BeadChip from the Framingham Heart Study (n = 1595). The prediction models were validated using data from the Women's Health Initiative (n = 883). We applied these models to genomewide association study (GWAS) data of 122 977 breast cancer patients and 105 974 controls to evaluate if the genetically predicted DNA methylation levels at CpG sites (CpGs) are associated with breast cancer risk. All statistical tests were two-sided.Results: Of the 62 938 CpG sites CpGs investigated, statistically significant associations with breast cancer risk were observed for 450 CpGs at a Bonferroni-corrected threshold of P less than 7.94 × 10-7, including 45 CpGs residing in 18 genomic regions, that have not previously been associated with breast cancer risk. Of the remaining 405 CpGs located within 500 kilobase flaking regions of 70 GWAS-identified breast cancer risk variants, the associations for 11 CpGs were independent of GWAS-identified variants. Integrative analyses of genetic, DNA methylation, and gene expression data found that 38 CpGs may affect breast cancer risk through regulating expression of 21 genes.Conclusion: Our new methodology can identify novel DNA methylation biomarkers for breast cancer risk and can be applied to other diseases. [ABSTRACT FROM AUTHOR]

Background: Lifetime use of bituminous ('smoky') coal is associated with nearly a 100-fold higher risk of lung cancer mortality compared with anthracite ('smokeless') coal use in rural Xuanwei, China, among women. Risk of mortality from ischaemic heart disease (IHD) and stroke for these coal types has not been evaluated.Methods: A cohort of 16 323 non-smoking women in Xuanwei, who were lifetime users of either smoky or smokeless coal, were followed up from 1976 to 2011. We estimated hazard ratios (HRs) and 95% confidence intervals (CI) to evaluate lifetime use of coal types and stoves in the home in relation to risk of IHD and stroke mortality.Results: Among lifetime users of smokeless coal, higher average exposure intensity (≥4 tons/year vs <2.5 tons/year, HR = 7.9, 95% CI = 3.5-17.8; Ptrend =<0.0001) and cumulative exposure (>64 ton-years vs ≤28 ton-years, HR = 6.5, 95% CI = 1.5-28.3; Ptrend =0.003) during follow-up and over their lifetime was associated with increased IHD mortality, and ventilated stove use dramatically reduced this risk (HR = 0.2, 95% CI 0.1-0.5). Higher cumulative exposure to smoky coal during follow-up showed positive associations with IHD mortality, but the evidence for other metrics was less consistent compared with associations with smokeless coal use.Conclusions: Higher use of smokeless coal, which is burned throughout China and is generally regarded to be a cleaner fuel type, is associated with IHD mortality. Use of cleaner fuels or stove interventions may be effective in reducing the increasing burden of IHD in developing regions that currently rely on smokeless coal for cooking and heating. [ABSTRACT FROM AUTHOR]

Purpose: Gallstone disease is known to be more common among obese individuals, particularly women. The effect of weight change and physical activity (PA) on gallstone risk, however, has seldom been examined. We evaluated the association of gallstone disease with weight, weight change, and PA among Chinese women in Shanghai. Methods: We conducted a case–control study nested in the Shanghai Women''s Health Study, including 8485 women with self-reported, physician-diagnosed, prevalent gallstone disease and 16,970 frequency-matched controls by birth year and age at gallstone diagnosis (4-year intervals). Information on height, weight history, PA, and other exposures was obtained by in-person interviews between 1997 and 2000. Exposures after gallstone diagnosis were truncated. Occupational PA (OPA) levels were derived from indices of sitting time and energy expenditure based on job history. Housework PA (HPA) was measured using daily hours spent on housework. Odds ratios (OR) and 95% confidence intervals (CI) were derived from logistic regression analyses. Results: Odds ratios for gallstone increased significantly with usual body mass index (BMI) and BMI at age 50, but not BMI at age 20. After adjusting for usual BMI, weight gain between ages 20 and 50 further increased the risk (OR=1.9, CI=1.6, 2.3 for subjects in the upper tertile of BMI increase). The effects of both overweight and weight gain were more prominent for postmenopausal women. Gallstone prevalence was inversely associated with HPA, with 30% reduction in risk for women with highest level of HPA (OR=0.70, CI=0.58, 0.84). Gallstone prevalence also was positively associated with increasing sitting time at work, although overall no significant association was found for OPA. HPA did not significantly modify weight-related gallstone associations. Conclusion: Overweight and weight gain increase the risk of gallstone in women, and regular PA may reduce risk. The effects of overweight, weight gain, and PA on gallstone prevalence appear to be independent of each other. [Copyright &y& Elsevier]

Introduction: Considering the joint association of neighborhood socioeconomic environment and individual-level health behaviors with health outcomes may help officials design effective disease prevention strategies. This study evaluates the joint influences of neighborhood socioeconomic environment and individual health behaviors on mortality in a cohort primarily comprising people with low individual-level SES.Methods: The prospective Southern Community Cohort Study includes 77,896 white and African American participants recruited in the years 2002-2009; 55% of participants had a household income <$15,000 at baseline interview. Mortality from cancer (n=2,471), cardiovascular diseases (n=3,005), and all-causes (n=10,099) was identified from the National Death Index through December 31, 2013 (median follow-up, 8 years). Data were analyzed in 2016 and 2017. Associations were assessed between mortality, a neighborhood deprivation index composed of 11 census tract-level variables, five health behaviors, and a composite healthy lifestyle score.Results: Living in a neighborhood with the greatest socioeconomic disadvantage was associated with higher all-cause mortality in both men (hazard ratio=1.41, 95% CI=1.27, 1.57) and women (hazard ratio=1.77, 95% CI=1.57, 2.00). Associations were attenuated after adjustment for individual-level SES and major risk factors (hazard ratio for men=1.09, 95% CI=0.98, 1.22, and hazard ratio for women=1.26, 95% CI=1.12, 1.42). The dose-response association between neighborhood disadvantage and mortality was less apparent among smokers. Nevertheless, individuals who lived in disadvantaged neighborhoods and had the unhealthiest lifestyle scores experienced the highest mortality.Conclusions: Disadvantaged neighborhood socioeconomic environments are associated with increased mortality in a cohort of individuals of low SES. Positive individual-level health behaviors may help negate the adverse effect of disadvantage on mortality. [ABSTRACT FROM AUTHOR]

Purpose: 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. Methods: 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 40–74 years 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. Results: 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 10 mg/day increase in isoflavone and each 50 g/day increase in soy food intake were 0.81 (0.70–0.94) and 0.84 (0.73–0.96), respectively. Conclusion: Higher intake of isoflavone and soy food was associated with lower risk of lung adenocarcinoma in never smokers. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxane chemotherapy. We investigated the associations of demographic and treatment variables with the risk of developing CIPN using electronic health record data. We found higher doses, more taxane cycles, female sex, overweight and obesity, or a history of diabetes were associated with developing CIPN in patients treated with taxane, while concurrent chemotherapy or concurrent radiotherapy were related to a reduced risk. Further studies are needed to uncover the underlying reasons for the observed associations. Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common therapeutic complication affecting cancer patients' quality-of-life. We evaluated clinical characteristics, demographics, and lifestyle factors in association with CIPN following taxane treatment. Methods: Data were extracted from the electronic health record of 3387 patients diagnosed with a primary cancer and receiving taxane (i.e., paclitaxel or docetaxel) at Vanderbilt University Medical Center. Neuropathy was assessed via a validated computer algorithm. Univariate and multivariate regression models were applied to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) of CIPN-associated factors. Results: Female sex (OR = 1.28, 95% CI = 1.01–1.62), high body-mass index (BMI) (OR = 1.31, 95% CI = 1.06–1.61 for overweight, and OR = 1.49, 95% CI = 1.21–1.83 for obesity), diabetes (OR = 1.66, 95% CI = 1.34–2.06), high mean taxane dose (OR = 1.05, 95% CI = 1.03–1.08 per 10 mg/m2), and more treatment cycles (1.12, 95% CI = 1.10–1.14) were positively associated with CIPN. Concurrent chemotherapy (OR = 0.74, 95% CI = 0.58–0.94) and concurrent radiotherapy (OR = 0.77, 95% CI = 0.59–1.00) were inversely associated with CIPN. Obesity and diabetes both had a stronger association with docetaxel CIPN compared to paclitaxel, although interaction was only significant for diabetes and taxane (p = 0.019). Increased BMI was associated with CIPN only among non-diabetic patients (OR:1.34 for overweight and 1.68 for obesity), while diabetes increased CIPN risk across all BMI strata (ORs were 2.65, 2.41, and 2.15 for normal weight, overweight, and obese, respectively) compared to normal-weight non-diabetic patients (p for interaction = 0.039). Conclusions: Female sex, obesity, and diabetes are significantly associated with taxine-induced CIPN. Further research is needed to identify clinical and pharmacologic strategies to prevent and mitigate CIPN in at-risk patient populations. [ABSTRACT FROM AUTHOR]