The Time-Dependent Association Between Irritable Bowel Syndrome and All-Cause and Cause-Specific Mortality: A Prospective Cohort Study Within the UK Biobank.

INTRODUCTION: Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, but few studies have evaluated mortality risks among individuals with IBS. We explored the association between IBS and all-cause and cause-specific mortality in the UK Biobank. METHODS: We included 502,369 participants from the UK Biobank with mortality data through 2022. IBS was defined using baseline self-report and linkage to primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality using multivariable Cox proportional hazards regression models within partitioned follow-up time categories (0-5, >5-10, and >10 years). RESULTS: A total of 25,697 participants (5.1%) had a history of IBS at baseline. After a median follow-up of 13.7 years, a total of 44,499 deaths occurred. Having an IBS diagnosis was strongly associated with lower risks of all-cause (HR = 0.70, 95% CI = 0.62-0.78) and all-cancer (HR = 0.69, 95% CI = 0.60-0.79) mortality in the first 5 years of follow-up. These associations were attenuated over follow-up, but even after 10 years of follow-up, associations remained inverse (all-cause: HR = 0.89, 95% CI = 0.84-0.96; all-cancer: HR = 0.87, 95% CI = 0.78-0.97) after full adjustment. Individuals with IBS had decreased risk of mortality from breast, prostate, and colorectal cancers in some of the follow-up time categories. DISCUSSION: We found that earlier during follow-up, having diagnosed IBS was associated with lower mortality risk, and the association attenuated over time. Additional studies to understand whether specific factors, such as lifestyle and healthcare access, explain the inverse association between IBS and mortality are needed.

Dental health and lung cancer risk in the Golestan Cohort Study.

BACKGROUND: Poor oral health has been linked to various systemic diseases, including multiple cancer types, but studies of its association with lung cancer have been inconclusive. METHODS: We examined the relationship between dental status and lung cancer incidence and mortality in the Golestan Cohort Study, a large, prospective cohort of 50,045 adults in northeastern Iran. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between three dental health measures (i.e., number of missing teeth; the sum of decayed, missing, or filled teeth (DMFT); and toothbrushing frequency) and lung cancer incidence or mortality with adjustment for multiple potential confounders, including cigarette smoking and opium use. We created tertiles of the number of lost teeth/DMFT score in excess of the loess adjusted, age- and sex-specific predicted numbers, with subjects with the expected number of lost teeth/DMFT or fewer as the reference group. RESULTS: During a median follow-up of 14 years, there were 119 incident lung cancer cases and 98 lung cancer deaths. Higher DMFT scores were associated with a progressively increased risk of lung cancer (linear trend, p = 0.011). Compared with individuals with the expected DMFT score or less, the HRs were 1.27 (95% CI: 0.73, 2.22), 2.15 (95% CI: 1.34, 3.43), and 1.52 (95% CI: 0.81, 2.84) for the first to the third tertiles of DMFT, respectively. The highest tertile of tooth loss also had an increased risk of lung cancer, with a HR of 1.68 (95% CI: 1.04, 2.70) compared with subjects with the expected number of lost teeth or fewer (linear trend, p = 0.043). The results were similar for lung cancer mortality and did not change substantially when the analysis was restricted to never users of cigarettes or opium. We found no associations between toothbrushing frequency and lung cancer incidence or mortality. CONCLUSION: Poor dental health indicated by tooth loss or DMFT, but not lack of toothbrushing, was associated with increased lung cancer incidence and mortality in this rural Middle Eastern population.

The association between poor oral health and risk of breast cancer in the UK Biobank.

PURPOSE: Specific oral health conditions may be risk factors for breast cancer. This study aimed to investigate the associations of oral health conditions with breast cancer risk. METHODS: A total of 234,363 women from the UK Biobank prospective cohort were included in this study. We examined the association of self-reported painful/bleeding gums, loose teeth, mouth ulcers, toothache, and use of dentures with the risk of breast cancer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations were calculated with adjustment for multiple confounders. RESULTS: No associations of self-reported painful/bleeding gums (HR = 1.04, 95% CI 0.98-1.10), loose teeth (HR = 0.92, 95% CI 0.82-1.02), mouth ulcers (HR = 0.99, 95% CI 0.93-1.06), toothache (HR = 1.03, 95% CI 0.92-1.14), or denture use (HR = 0.96, 95% CI 0.91-1.02) with breast cancer risk were found. No statistical heterogeneity was observed in analyses stratified by baseline smoking and menopausal status. CONCLUSION: We observed no association between self-reported oral health conditions with the risk of breast cancer. Additional research with clinical examinations or oral health biomarkers in diverse populations is warranted.

The oral microbiome and breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

Markers of metabolic health and gut microbiome diversity: findings from two population-based cohort studies.

AIMS/HYPOTHESIS: The gut microbiome is hypothesised to be related to insulin resistance and other metabolic variables. However, data from population-based studies are limited. We investigated associations between serologic measures of metabolic health and the gut microbiome in the Northern Finland Birth Cohort 1966 (NFBC1966) and the TwinsUK cohort. METHODS: Among 506 individuals from the NFBC1966 with available faecal microbiome (16S rRNA gene sequence) data, we estimated associations between gut microbiome diversity metrics and serologic levels of HOMA for insulin resistance (HOMA-IR), HbA1c and C-reactive protein (CRP) using multivariable linear regression models adjusted for sex, smoking status and BMI. Associations between gut microbiome diversity measures and HOMA-IR and CRP were replicated in 1140 adult participants from TwinsUK, with available faecal microbiome (16S rRNA gene sequence) data. For both cohorts, we used general linear models with a quasi-Poisson distribution and Microbiome Regression-based Kernel Association Test (MiRKAT) to estimate associations of metabolic variables with alpha- and beta diversity metrics, respectively, and generalised additive models for location scale and shape (GAMLSS) fitted with the zero-inflated beta distribution to identify taxa associated with the metabolic markers. RESULTS: In NFBC1966, alpha diversity was lower in individuals with higher HOMA-IR with a mean of 74.4 (95% CI 70.7, 78.3) amplicon sequence variants (ASVs) for the first quartile of HOMA-IR and 66.6 (95% CI 62.9, 70.4) for the fourth quartile of HOMA-IR. Alpha diversity was also lower with higher HbA1c (number of ASVs and Shannon's diversity, p < 0.001 and p = 0.003, respectively) and higher CRP (number of ASVs, p = 0.025), even after adjustment for BMI and other potential confounders. In TwinsUK, alpha diversity measures were also lower among participants with higher measures of HOMA-IR and CRP. When considering beta diversity measures, we found that microbial community profiles were associated with HOMA-IR in NFBC1966 and TwinsUK, using multivariate MiRKAT models, with binomial deviance dissimilarity p values of <0.001. In GAMLSS models, the relative abundances of individual genera Prevotella and Blautia were associated with HOMA-IR in both cohorts. CONCLUSIONS/INTERPRETATION: Overall, higher levels of HOMA-IR, CRP and HbA1c were associated with lower microbiome diversity in both the NFBC1966 and TwinsUK cohorts, even after adjustment for BMI and other variables. These results from two distinct population-based cohorts provide evidence for an association between metabolic variables and gut microbial diversity. Further experimental and mechanistic insights are now needed to provide understanding of the potential causal mechanisms that may link the gut microbiota with metabolic health.

Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study.

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.

Comparison of fecal and oral collection methods for studies of the human microbiota in two Iranian cohorts.

BACKGROUND: To initiate fecal and oral collections in prospective cohort studies for microbial analyses, it is essential to understand how field conditions and geographic differences may impact microbial communities. This study aimed to investigate the impact of fecal and oral sample collection methods and room temperature storage on collection samples for studies of the human microbiota. RESULTS: We collected fecal and oral samples from participants in two Iranian cohorts located in rural Yazd (n = 46) and urban Gonbad (n = 38) and investigated room temperature stability over 4 days of fecal (RNAlater and fecal occult blood test [FOBT] cards) and comparability of fecal and oral (OMNIgene ORAL kits and Scope mouthwash) collection methods. We calculated interclass correlation coefficients (ICCs) based on 3 alpha and 4 beta diversity metrics and the relative abundance of 3 phyla. After 4 days at room temperature, fecal stability ICCs and ICCs for Scope mouthwash were generally high for all microbial metrics. Similarly, the fecal comparability ICCs for RNAlater and FOBT cards were high, ranging from 0.63 (95% CI: 0.46, 0.75) for the relative abundance of Firmicutes to 0.93 (95% CI: 0.89, 0.96) for unweighted Unifrac. Comparability ICCs for OMNIgene ORAL and Scope mouthwash were lower than fecal ICCs, ranging from 0.55 (95% CI: 0.36, 0.70) for the Shannon index to 0.79 (95% CI: 0.69, 0.86) for Bray-Curtis. Overall, RNAlater, FOBT cards and Scope mouthwash were stable up to 4 days at room temperature. Samples collected using FOBT cards were generally comparable to RNAlater while the OMNIgene ORAL were less similar to Scope mouthwash. CONCLUSIONS: As microbiome measures for feces samples collected using RNAlater, FOBT cards and oral samples collected using Scope mouthwash were stable over four days at room temperature, these would be most appropriate for microbial analyses in these populations. However, one collection method should be consistently since each method may induce some differences.

Associations of periodontal disease and tooth loss with all-cause and cause-specific mortality in the Sister Study.

AIM: Studies have found that periodontal disease and tooth loss are associated with increased mortality; however, associations with cause-specific mortality and all-cause mortality within specific subgroups have not been thoroughly investigated. MATERIALS AND METHODS: We examined the association of self-reported periodontal disease and disease/decay-related tooth loss with subsequent all-cause and cause-specific mortality in the Sister Study, a prospective cohort study of 50,884 women aged 35-74 years at baseline, whose sister was diagnosed with breast cancer. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the associations were calculated with adjustment for relevant confounders. RESULTS: With a mean follow-up of 10.9 years (range 0.1-14.3), 2058 women died. Participants with periodontal disease had a slightly higher rate of all-cause mortality (HR = 1.08, 95% CI 0.98-1.19), while participants with tooth loss had an increased rate of all-cause mortality (HR = 1.15, 95% CI 1.05-1.26). For cause-specific mortality, women with tooth loss had increased rates of death from circulatory system diseases, respiratory system diseases, and endocrine/metabolic diseases. Results varied in stratified models, but no heterogeneity across strata was found. CONCLUSIONS: In this large prospective study, periodontal disease and tooth loss were associated with all-cause and certain specific cause-specific mortality outcomes.

Microbial characterization of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma from a high-risk region of China.

BACKGROUND: Little is known about the microbiota and upper gastrointestinal tumors. Esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) occur in adjacent organs, co-occur geographically, and share many risk factors despite being of different tissue types. METHODS: This study characterized the microbial communities of paired tumor and nontumor samples from 67 patients with ESCC and 36 patients with GCA in Henan, China. DNA was extracted with the MoBio PowerSoil kit. The V4 region of the 16S ribosomal RNA gene was sequenced with MiniSeq and was processed with Quantitative Insights Into Microbial Ecology 1. The linear discriminant analysis effect size method was used to identify differentially abundant microbes, the Wilcoxon rank-sum test was used to test α diversity differences, and permutational multivariate analysis of variance was used to test for differences in ß diversity. RESULTS: The microbial environments of ESCC and GCA tissues were all composed primarily of Firmicutes, Bacteroidetes, and Proteobacteria. ESCC tumor tissues contained more Fusobacterium (3.2% vs 1.3%) and less Streptococcus (12.0% vs 30.2%) than nontumor tissues. GCA nontumor tissues had a greater abundance of Helicobacter (60.5% vs 11.8%), which may have been linked to the lower α diversity (58.0 vs 102.5; P = .0012) in comparison with tumor tissues. A comparison of ESCC and GCA nontumor tissues showed that the microbial composition (P = .0040) and the α diversity (87.0 vs 58.0; P = .00052) were significantly different. No significant differences were detected for α diversity within ESCC and GCA tumor tissues. CONCLUSIONS: This study showed differences in the microbial compositions of paired ESCC and GCA tumor and nontumor tissues and differences by organ site. Large-scale, prospective cohort studies are needed to confirm these findings.

Quantification of Human Microbiome Stability Over 6 Months: Implications for Epidemiologic Studies.

Temporal variation in microbiome measurements can reduce statistical power in research studies. Quantification of this variation is essential for designing studies of chronic disease. We analyzed 16S ribosomal RNA profiles in paired biological specimens separated by 6 months from 3 studies conducted during 1985-2013 (a National Cancer Institute colorectal cancer study, a Costa Rica study, and the Human Microbiome Project). We evaluated temporal stability by calculating intraclass correlation coefficients (ICCs). Sample sizes needed in order to detect microbiome differences between equal numbers of cases and controls for a nested case-control design were calculated on the basis of estimated ICCs. Across body sites, 12 phylum-level ICCs were greater than 0.5. Similarly, 11 alpha-diversity ICCs were greater than 0.5. Fecal beta-diversity estimates had ICCs over 0.5. For a single collection with most microbiome metrics, detecting an odds ratio of 2.0 would require 300-500 cases when matching 1 case to 1 control at P = 0.05. Use of 2 or 3 sequential specimens reduces the number of required subjects by 40%-50% for low-ICC metrics. Relative abundances of major phyla and alpha-diversity metrics have low temporal stability. Thus, detecting associations of moderate effect size with these metrics will require large sample sizes. Because beta diversity for feces is reasonably stable over time, smaller sample sizes can detect associations with community composition. Sequential prediagnostic specimens from thousands of prospectively ascertained cases are required to detect modest disease associations with particular microbiome metrics.

Sleep characteristics, light at night and breast cancer risk in a prospective cohort.

Increasing numbers of women in the US are getting too little sleep. Inadequate sleep has been associated with impaired metabolic function and endocrine disruption. Sister Study cohort participants (n = 50,884), completed baseline and follow-up questionnaires on sleep patterns. Incident breast cancers estrogen receptor (ER) status of the tumor were ascertained from questionnaires and medical records. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs). Analyses of sleep characteristics reported at the first follow-up interview included only participants who were breast cancer-free at time of follow-up interview. Over ∼7 years of follow-up, 2,736 breast cancer cases (invasive and ductal carcinoma in situ) were diagnosed. There was little evidence that usual sleep duration or other sleep characteristics were associated with breast cancer. However, relative to those with no difficulty sleeping, women who reported having difficulty sleeping ≥ 4 nights a week were at an increased risk of overall (HR = 1.32, 95% CI: 1.09-1.61) and postmenopausal breast cancer (HR = 1.51, 95% CI 1.24-1.85). Risk of ER+ invasive cancer was elevated for women who reported having a light or television on in the room while sleeping (HR = 1.20, 95% CI: 0.97-1.47) or who typically got less sleep than they needed to feel their best (HR = 1.21, 95% CI: 0.98-1.50). In our study, most sleep characteristics, including sleep duration, were not associated with an increased risk although higher risk was observed for some markers of inadequate or poor quality sleep.

Comparison of Collection Methods for Fecal Samples in Microbiome Studies.

Prospective cohort studies are needed to assess the relationship between the fecal microbiome and human health and disease. To evaluate fecal collection methods, we determined technical reproducibility, stability at ambient temperature, and accuracy of 5 fecal collection methods (no additive, 95% ethanol, RNAlater Stabilization Solution, fecal occult blood test cards, and fecal immunochemical test tubes). Fifty-two healthy volunteers provided fecal samples at the Mayo Clinic in Rochester, Minnesota, in 2014. One set from each sample collection method was frozen immediately, and a second set was incubated at room temperature for 96 hours and then frozen. Intraclass correlation coefficients (ICCs) were calculated for the relative abundance of 3 phyla, 2 alpha diversity metrics, and 4 beta diversity metrics. Technical reproducibility was high, with ICCs for duplicate fecal samples between 0.64 and 1.00. Stability for most methods was generally high, although the ICCs were below 0.60 for 95% ethanol in metrics that were more sensitive to relative abundance. When compared with fecal samples that were frozen immediately, the ICCs were below 0.60 for the metrics that were sensitive to relative abundance; however, the remaining 2 alpha diversity and 3 beta diversity metrics were all relatively accurate, with ICCs above 0.60. In conclusion, all fecal sample collection methods appear relatively reproducible, stable, and accurate. Future studies could use these collection methods for microbiome analyses.

Comparison of Fecal Collection Methods for Microbiota Studies in Bangladesh.

To our knowledge, fecal microbiota collection methods have not been evaluated in low- and middle-income countries. Therefore, we evaluated five different fecal sample collection methods for technical reproducibility, stability, and accuracy within the Health Effects of Arsenic Longitudinal Study (HEALS) in Bangladesh. Fifty participants from the HEALS provided fecal samples in the clinic which were aliquoted into no solution, 95% ethanol, RNAlater, postdevelopment fecal occult blood test (FOBT) cards, and fecal immunochemical test (FIT) tubes. Half of the aliquots were frozen immediately at -80°C (day 0) and the remaining samples were left at ambient temperature for 96 h and then frozen (day 4). Intraclass correlation coefficients (ICC) were calculated for the relative abundances of the top three phyla, for two alpha diversity measures, and for four beta diversity measures. The duplicate samples had relatively high ICCs for technical reproducibility at day 0 and day 4 (range, 0.79 to 0.99). The FOBT card and samples preserved in RNAlater and 95% ethanol had the highest ICCs for stability over 4 days. The FIT tube had lower stability measures overall. In comparison to the "gold standard" method using immediately frozen fecal samples with no solution, the ICCs for many of the microbial metrics were low, but the rank order appeared to be preserved as seen by the Spearman correlation. The FOBT cards, 95% ethanol, and RNAlater were effective fecal preservatives. These fecal collection methods are optimal for future cohort studies, particularly in low- and middle-income countries.IMPORTANCE The collection of fecal samples in prospective cohort studies is essential to provide the opportunity to study the effect of the human microbiota on numerous health conditions. However, these collection methods have not been adequately tested in low- and middle-income countries. We present estimates of technical reproducibility, stability at ambient temperature for 4 days, and accuracy comparing a "gold standard" for fecal samples in no solution, 95% ethanol, RNAlater, postdevelopment fecal occult blood test cards, and fecal immunochemical test tubes in a study conducted in Bangladesh. Fecal occult blood test cards and fecal samples stored in 95% ethanol or RNAlater adequately preserve fecal samples in this setting. Therefore, new studies in low- and middle-income countries should include collection of fecal samples using fecal occult blood test cards, 95% ethanol, or RNAlater for prospective cohort studies.

Epidemiologic studies of the human microbiome and cancer.

The human microbiome, which includes the collective genome of all bacteria, archaea, fungi, protists, and viruses found in and on the human body, is altered in many diseases and may substantially affect cancer risk. Previously detected associations of individual bacteria (e.g., Helicobacter pylori), periodontal disease, and inflammation with specific cancers have motivated studies considering the association between the human microbiome and cancer risk. This short review summarises microbiome research, focusing on published epidemiological associations with gastric, oesophageal, hepatobiliary, pancreatic, lung, colorectal, and other cancers. Large, prospective studies of the microbiome that employ multidisciplinary laboratory and analysis methods, as well as rigorous validation of case status, are likely to yield translational opportunities to reduce cancer morbidity and mortality by improving prevention, screening, and treatment.

Coffee Drinking Is Widespread in the United States, but Usual Intake Varies by Key Demographic and Lifestyle Factors.

BACKGROUND: Despite widespread popularity and possible health effects, the prevalence and distribution of coffee consumption in US adults are poorly characterized. OBJECTIVE: We sought to estimate usual daily coffee intakes from all coffee-containing beverages, including decaffeinated and regular coffee, among US adults according to demographic, socioeconomic, and health-related factors. METHODS: Dietary intake data from ≤2 nonconsecutive 24-h dietary recalls and a food-frequency questionnaire administered during the NHANES 2003-2006 were used to estimate the person-specific probability of consuming coffee on a particular day and the usual amount consumed on consumption days. Trends in population mean coffee consumption over time were evaluated by using multiple linear regression and 1-d 24-h recall data from NHANES 2003-2012. Analyses were weighted to be representative of the US adult population aged ≥20 y. RESULTS: An estimated 154 million adults, or 75% of the US population, aged ≥20 y reported drinking coffee; 49% reported drinking coffee daily. Prevalence did not vary by sex, education, income, or self-reported general health (all P ≥ 0.05) but did vary by age, race/ethnicity, smoking status, and alcohol drinking (all P < 0.05). Among coffee drinkers, the mean ± SE usual intake was 14.1 ± 0.5 fluid ounces/d (417 ± 15 mL/d). Mean usual intakes were higher in men than women, in older age groups than in those aged 20 to <30 y, in non-Hispanic whites than in non-Hispanic blacks or Hispanic/other races, in smokers than in never smokers, and in daily alcohol consumers than in nonconsumers (all P < 0.05). Population mean coffee consumption was stable from 2003 to 2012 (P-trend = 0.09). CONCLUSIONS: Coffee is widely consumed in the United States, with usual intakes varying by lifestyle and demographic factors, most notably by age. Longitudinal studies are needed to determine whether observed differences by age reflect birth cohort effects or changes in drinking patterns over the lifetime.

Association between tobacco use and the upper gastrointestinal microbiome among Chinese men.

PURPOSE: Tobacco causes many adverse health conditions and may alter the upper gastrointestinal (UGI) microbiome. However, the few studies that studied the association between tobacco use and the microbiome were small and underpowered. Therefore, we investigated the association between tobacco use and the UGI microbiome in Chinese men. METHODS: We included 278 men who underwent esophageal cancer screening in Henan Province, China. Men were categorized as current, former, or never smokers from questionnaire data. UGI tract bacterial cells were characterized using the Human Oral Microbial Identification Microarray. Counts of unique bacterial species and genera estimated alpha diversity. For beta diversity, principal coordinate (PCoA) vectors were generated from an unweighted UniFrac distance matrix. Polytomous logistic regression models were used for most analyses. RESULTS: Of the 278 men in this study, 46.8% were current smokers and 12.6% were former smokers. Current smokers tended to have increased alpha diversity (mean 42.3 species) compared to never smokers (mean 38.9 species). For a 10 species increase, the odds ratio (OR) for current smoking was 1.29 (95% CI 1.04-1.62). Beta diversity was also associated with current smoking. The first two PCoA vectors were strongly associated with current smoking (PCoA1 OR 0.66; 95% CI 0.51-0.87; PCoA2 OR 0.73; 95% CI 0.56-0.95). Furthermore, Dialister invisus and Megasphaera micronuciformis were more commonly detected in current smokers than in never smokers. CONCLUSIONS: Current smoking was associated with both alpha and beta diversity in the UGI tract. Future work should consider how the UGI microbiome is associated with smoking-related diseases.

Correlates of self-reported dietary cruciferous vegetable intake and urinary isothiocyanate from two cohorts in China.

OBJECTIVE: To assess correlations between cruciferous vegetable intake and urinary isothiocyanate (ITC) level, in addition to glutathione S-transferase (GST) genotypes and other individual factors. DESIGN: The study included cohort participants whose urinary ITC levels had been previously ascertained. Urinary ITC was assessed using HPLC. Usual dietary intake of cruciferous vegetables was assessed using a validated FFQ and total dietary ITC intake was calculated. Recent cruciferous vegetable intake was determined. GST genotypes were assessed using duplex real-time quantitative PCR assays. Spearman correlations were calculated between the covariates and urinary ITC levels and linear regression analyses were used to calculate the mean urinary ITC excretion according to GST genotype. SETTING: Urban city in China. SUBJECTS: The study included 3589 women and 1015 men from the Shanghai Women's and Men's Health Studies. RESULTS: Median urinary ITC level was 1.61 nmol/mg creatinine. Self-reported usual cruciferous vegetable intake was weakly correlated with urinary ITC level (r s=0.1149; P<0.0001), while self-reported recent intake was more strongly correlated with urinary ITC (r s=0.2591; P<0.0001). Overall, the GST genotypes were not associated with urinary ITC level, but significant differences according to genotype were observed among current smokers and participants who provided an afternoon urine sample. Other factors, including previous gastrectomy or gastritis, were also related to urinary ITC level. CONCLUSIONS: The study suggests that urinary secretion of ITC may provide additional information on cruciferous vegetable intake and that GST genotypes are related to urinary ITC level only in some subgroups.

Age at menarche and risk of ovarian cancer: a meta-analysis of epidemiological studies.

Epidemiological studies have reported inconsistent associations between menarcheal age and ovarian cancer risk. To our knowledge, a meta-analysis for the association between menarcheal age and ovarian cancer has not been reported. Relevant published studies of menarcheal age and ovarian cancer were identified using MEDLINE, EMBASE and Web of Science through the end of April 2012. Two authors (T-T.G. and Q-J.W.) independently assessed eligibility and extracted data. We pooled the relative risks (RRs) from individual studies using a random-effects model and performed heterogeneity and publication bias analyses. A total of 27 observational studies consisting of 22 case-control and five cohort studies were included in our analysis. In a pooled analysis of all studies, a statistically significant inverse association was observed between menarcheal age (for the oldest compared to the youngest category) and ovarian cancer risk (RR = 0.85; 95% confidence interval [CI] = 0.75-0.97). The pooled RRs of ovarian cancer for the oldest versus the youngest categories of menarcheal age in prospective and case-control studies were 0.89 (95% CI = 0.76-1.03) and 0.84 (95% CI = 0.70-0.99), respectively. Inverse associations between menarcheal age and ovarian cancer risk were observed in most subgroups; however, the significant association was restricted to invasive and borderline serous ovarian cancer. In conclusion, findings from this meta-analysis support that menarcheal age was inversely associated with the risk of ovarian cancer. More large studies are warranted to stratify these results by different cancer grading and histotype of ovarian cancer.

Fruit and vegetable intake and the risk of colorectal cancer: results from the Shanghai Men's Health Study.

PURPOSE: The observed associations of fruit and vegetable consumption with the risk of colorectal cancer have been inconsistent. Therefore, we aimed to evaluate the association of fruit and vegetable consumption with the risk of colorectal cancer among Chinese men. METHODS: 61,274 male participants aged 40-74 years were included. A validated food frequency questionnaire was administered to collect information on usual dietary intake, including 8 fruits and 38 vegetables commonly consumed by residents of Shanghai. Follow-up for diagnoses of colon or rectal cancer was available through 31 December 2010. Dietary intakes were analyzed both as categorical and continuous variables. Multivariable-adjusted hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were calculated for colorectal, colon, and rectal cancers using Cox proportional hazards models. RESULTS: After 390,688 person-years of follow-up, 398 cases of colorectal cancer (236 colon and 162 rectal) were observed in the cohort. Fruit consumption was inversely associated with the risk of colorectal cancer (fifth vs. first quintile HR 0.67; 95 % CI 0.48, 0.95; p trend = 0.03), whereas vegetable intake was not significantly associated with risk. The associations for subgroups of fruits and legumes, but not other vegetable categories, were generally inversely associated with the risk of colon and rectal cancers. CONCLUSIONS: Fruit intake was generally inversely associated with the risk of colorectal cancer, whereas vegetable consumption was largely unrelated to risk among middle-aged and older Chinese men.

Variants in CCK and CCKAR genes to susceptibility to biliary tract cancers and stones: a population-based study in Shanghai, China.

BACKGROUND AND AIM: Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (CCK) is an important modulator of gallbladder motility which functions by activating CCK type-A receptor (CCKAR). The aim of this study was to determine whether genetic variants in CCK and CCKAR are associated with the risk of biliary tract cancers and stones. METHODS: We investigated the associations between nine single nucleotide polymorphisms in CCK and CCKAR in a population-based case-control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct, and 53 ampulla of Vater cancer cases), 429 biliary stone cases, and 447 population controls in Shanghai, China. RESULTS: We found that women with the CCKAR rs1800855 AA genotype had an increased risk of gallbladder cancer (odds ratio = 2.37, 95% confidence interval (CI): 1.36-4.14) compared with subjects with the TT genotype, and remained significant after Bonferroni correction (P = 0.0056). Additionally, female carriers of the CCKAR haplotype C-T-C-T (rs2071011-rs915889-rs3822222-rs1800855) had a reduced risk of gallbladder cancer (odds ratio = 0.61, 95% confidence interval: 0.43-0.86) compared with those with the G-C-C-A haplotype; the association also remained significant after Bonferroni correction. CONCLUSIONS: These findings suggest that variants in the CCKAR gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.