Helicobacter pylori (H. pylori) infection is considered the leading cause of gastric cancer. Gastric cancer is currently a common cancer with high incidence and mortality rates, but it is expected ...that the incidence rate will gradually decrease as the H. pylori infection prevalence decreases in the future. When evaluating the effectiveness of gastric cancer prevention strategies, it is essential to note the differences in long‐term cumulative risks between H. pylori‐infected and uninfected populations, but this has not yet been precisely evaluated. In our study, we aimed to estimate the cumulative incidence risks of developing gastric cancer from birth to 85 years among H. pylori‐infected and uninfected populations by using population‐based cancer registry data and birth year‐specific H. pylori infection prevalence rates. Death from gastric cancer and other causes of death were considered in the estimations of the adjusted cumulative incidence risks stratified by sex and H. pylori infection status. After performing 5000 Monte Carlo simulations with repeated random sampling using observed cancer incidence in selected three prefectures (Fukui, Nagasaki, Yamagata) of prefectural population‐based cancer registry in Japan, the mean adjusted cumulative incidence risk for gastric cancer in the H. pylori‐infected population was 17.0% for males and 7.7% for females and 1.0% for males and 0.5% for females in the uninfected population. These results calculated with Japanese cancer registry data may be useful in considering and evaluating future prevention strategies for gastric cancer in Japan.
What's new?
Helicobacter pylori infection is considered the leading cause of gastric cancer. This study estimated the cumulative incidence risk for gastric cancer from birth to 85 years of age, stratified by H. pylori infection status, for the first time in Japan. The cumulative risk among H. pylori‐infected individuals was 17.0% in males and 7.7% in females, after adjusting for gastric cancer incidence and other causes of death. The cumulative risk in the population without H. pylori infection was low. These results offer essential information for future cost‐effectiveness and cost‐benefit analyses and new gastric cancer prevention programs in Japan.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background. New serum pepsinogen (PG) criteria have been shown to indicate more accurately infection with Helicobacter pylori (H. pylori). We sought to improve risk classification for gastric cancer ...by adopting the new PG criteria with the addition of an H. pylori antibody test. Methods. The study participants were 275 patients with gastric cancer and 275 apparently healthy controls from case–control study data. We cross-sectionally compared the results of gastric cancer risk classifications that were based on a combination of the new PG criteria (PG II ≥ 10 ng/mL or PG I/II ≤ 5) and an H. pylori antibody test with those that were based on a combination of the conventional criteria (PG I ≤ 70 ng/mL and PG I/PG II ≤ 3) and an H. pylori antibody test. Results. Applying the conventional criteria resulted in 89 controls being classified as low risk. Applying the new criteria resulted in 23 controls (bootstrapped 95% confidence intervals CI: 14, 32) being additionally classified as high risk. Eight patients with gastric cancer were classified as low risk using the conventional criteria; however, six of these patients were classified as high risk by the new criteria (bootstrapped 95% CI: 2, 11). Conclusions. Compared with the conventional criteria, the new PG criteria with H. pylori antibody reduced instances of gastric cancer cases being misclassified as low risk. These findings suggest that the new PG criteria may help identify individuals at high risk of developing gastric cancer.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The purpose of this study was to evaluate the reproducibility and validity of a short food frequency questionnaire (FFQ) for food group intake in Japan, the reproducibility and partial validity of ...which were previously confirmed for nutrients.
A total of 288 middle-aged healthy volunteers from 11 different areas of Japan provided nonconsecutive 3-day weighed dietary records (DRs) at 3-month intervals over four seasons. We evaluated reproducibility based on the first (FFQ1) and second (FFQ2) questionnaires and their validity against the DRs by comparing the intake of 20 food groups. Spearman's rank correlation coefficients (SRs) were calculated between energy-adjusted intake from the FFQs and that from the DRs.
The intake of 20 food groups estimated from the two FFQs was mostly equivalent. The median energy-adjusted SRs between the FFQ1 and FFQ2 were 0.61 (range 0.38-0.86) for men and 0.66 (0.45-0.84) for women. For validity, the median de-attenuated SRs between DRs and the FFQ1 were 0.51 (0.17-0.76) for men and 0.47 (0.23-0.77) for women. Compared with the DRs, the proportion of cross-classification into exact plus adjacent quintiles with the FFQ1 ranged from 58 to 86% in men and from 57 to 86% in women. According to the robust Z scores and the Bland-Altman plot graphs, the underestimation errors in the FFQ1 tended to be greater in individuals with high mean levels of consumption for meat for men and for other vegetables for both men and women.
The FFQ demonstrated high reproducibility and reasonable validity for food group intake. This questionnaire is short and remains appropriate for identifying associations between diet and health/disease among adults in Japan.
Background: Although beneficial associations have been reported between moderate alcohol intake and the serum lipid profile, it is unclear whether polymorphisms in alcohol-metabolizing enzymes can ...modify these associations. Here, we assessed the effects of ADH1B His48Arg (rs1229984), ALDH2 Glu504Lys (rs671), and their combination on these associations. Furthermore, we examined if the findings for ALDH2 could be replicated. Methods: We categorized 889 male participants in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study into two groups based on presence or absence of minor allele(s) or four groups based on genotype combinations. We performed regression analyses of serum lipid concentrations on alcohol intake, with multivariable adjustment. The replication study was conducted among 2,562 men in the Shizuoka part of the J-MICC Study. Results: The ALDH2 Glu/Lys or Lys/Lys groups showed significant decreases in serum low-density lipoprotein (LDL) cholesterol with increasing alcohol consumption; the coefficient per intake increase of 10 g/day was −2.49 mg/dL (95% confidence interval CI, −3.85 to −1.13), and a significant interaction with the polymorphism was confirmed (P for interaction = 0.006). This inverse correlation was more evident among the ADH1B His/His + ALDH2 Glu/Lys or Lys/Lys groups (−3.24 mg/dL, 95% CI, −5.03 to −1.45). Serum triglycerides were positively associated with alcohol consumption in the ADH1B His/His group (P for interaction = 0.020). The stronger association between serum LDL cholesterol and alcohol consumption in the ALDH2 Glu/Lys or Lys/Lys groups was replicated. Conclusions: The ALDH2 Glu504Lys polymorphism can modify the association between alcohol intake and serum LDL cholesterol in Japanese men.
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FFLJ, NUK, ODKLJ, UL, UM, UPUK
Abstract
Background
In Japan, there are ongoing efforts to shift the gastric cancer prevention and control policy priorities from barium-based screening to Helicobacter pylori (H. pylori)-oriented ...primary prevention. A comprehensive summary of the evidence regarding the effects of H. pylori eradication on the risk of gastric cancer could inform policy decisions.
Methods
We conducted a systematic review and meta-analysis of published studies evaluating the effectiveness of H. pylori eradication for the prevention of gastric cancer in otherwise healthy individuals (primary prevention) and early gastric cancer patients (tertiary prevention).
Results
In total, 19 studies were included. Three moderate-quality observational cohort studies showed that H. pylori eradication may be associated with a decreased risk of gastric cancer in healthy asymptomatic Japanese people. There is moderate certainty regarding the effectiveness of H. pylori eradication in patients with gastrointestinal diseases, such as peptic ulcers. A meta-analysis of 10 observational studies with otherwise healthy individuals (mainly peptic ulcer patients) yielded an overall risk ratio of 0.34 (95% CI: 0.25–0.46). Regarding tertiary prevention, the overall risk ratio for developing metachronous gastric cancer was 0.50 (95% CI: 0.39–0.66) in the eradication group in a meta-analysis of nine studies involving early gastric cancer patients who underwent endoscopic resection.
Conclusion
H. pylori eradication is effective in preventing gastric cancer in the Japanese population, regardless of symptoms. Well-designed, large cohort studies are warranted to determine the long-term efficacy and safety of H. pylori eradication in the context of reducing the gastric cancer burden through population-based screening and treatment.
Our systematic review concluded that H. pylori eradication is effective in preventing gastric cancer in the Japanese population. Large cohort studies are warranted to determine the long-term efficacy and safety.
PURPOSEAlthough several genetic factors may play a role in leisure-time exercise behavior, there is currently no evidence of a significant genomewide association, and candidate gene replication ...studies have produced inconsistent results.
METHODSWe conducted a two-stage genomewide association study and candidate single-nucleotide polymorphisms (SNP) association study on leisure-time exercise behavior using 13,980 discovery samples from the Japan Multi-Institutional Collaborative Cohort (J-MICC) study, and 2036 replication samples from the Hospital-based Epidemiologic Research Program at Aichi Cancer Center-2 study. Leisure-time physical activity was measured using a self-administered questionnaire that inquired about the type, frequency and duration of exercise. Participants with ≥4 MET·h·wk of leisure-time physical activity were defined as exhibiting leisure-time exercise behavior. Association testing using mixed linear regression models was performed on the discovery and replication samples, after which the results were combined in a meta-analysis. In addition, we tested six candidate genetic variants derived from previous genomewide association study.
RESULTSWe found that one novel SNP (rs10252228) located in the intergenic region between NPSR1 and DPY19L1 was significantly associated with leisure-time exercise behavior in discovery samples. This association was also significant in replication samples (combined P value by meta-analysis = 2.2 × 10). Several SNP linked with rs10252228 were significantly associated with gene expression of DPY19L1 and DP19L2P1 in skeletal muscle, heart, whole blood, and the nervous system. Among the candidate SNP, rs12612420 in DNAPTP6 demonstrated nominal significance in discovery samples but not in replication samples.
CONCLUSIONSWe identified a novel genetic variant associated with regular leisure-time exercise behavior. Further functional studies are required to validate the role of these variants in exercise behavior.
Although self-rated health (SRH) independently predicts mortality, the biological background of this association remains unexplained. This study aimed to examine the association between SRH and serum ...high-sensitivity C-reactive protein (hsCRP) level.
Subjects were 899 participants aged 35-69 years (237 men and 662 women) in the Daiko Study, part of the Japan Multi-Institutional Collaborative Cohort Study. They were enrolled from 2008 to 2010. Of the subjects, 666 participated in a second survey 5 years later. Lifestyle factors and SRH were assessed using a self-administered questionnaire. Serum hsCRP level was measured using a latex-enhanced immunonephelometric assay. The association between SRH and serum hsCRP level was evaluated using a general linear model with covariates. We further longitudinally investigated whether higher serum hsCRP level at baseline predicts poor SRH after 5 years using an unconditional logistic regression model.
A higher serum hsCRP level was significantly associated with poor SRH at baseline after adjusting for covariates (p for trend = 0.023). The age- and sex-adjusted odds ratio and 95% confidence interval (CI) for poor SRH after 5 years was 1.45 (95% CI: 0.76-2.78) for the highest tertile compared with the lowest tertile of serum hsCRP level at baseline with a significant linear trend (p for trend = 0.033), although the risk increase disappeared after adjustment for other covariates.
The present study demonstrated that poor SRH is cross-sectionally associated with higher serum hsCRP level. However, the longitudinal data did not support the relationship between serum hsCRP level at baseline and future SRH. Further longitudinal studies that include data on mortality and multiple inflammatory markers are warranted to elucidate the possible role of low-grade inflammation in the association between SRH and mortality risk.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The aim of this study was to further examine the relationship between milk intake and stroke mortality among the Japanese population. We used data from the Japan Collaborative Cohort (JACC) Study ...(total number of participants = 110,585, age range: 40-79) to estimate the posterior acceleration factors (AF) as well as the hazard ratios (HR) comparing individuals with different milk intake frequencies against those who never consumed milk at the study baseline. These estimations were computed through a series of Bayesian survival models that employed a Markov Chain Monte Carlo simulation process. In total, 100,000 posterior samples were generated separately through four independent chains after model convergency was confirmed. Posterior probabilites that daily milk consumers had lower hazard or delayed mortality from strokes compared to non-consumers was 99.0% and 78.0% for men and women, respectively. Accordingly, the estimated posterior means of AF and HR for daily milk consumers were 0.88 (95% Credible Interval, CrI: 0.81, 0.96) and 0.80 (95% CrI: 0.69, 0.93) for men and 0.97 (95% CrI: 0.88, 1.10) and 0.95 (95% CrI: 0.80, 1.17) for women. In conclusion, data from the JACC study provided strong evidence that daily milk intake among Japanese men was associated with delayed and lower risk of mortality from stroke especially cerebral infarction.
Serum Helicobacter pylori (H. pylori) antibody kits (LZ and LIA) using the latex agglutination immunoassay method are commercially available, but few studies have been performed to determine their ...diagnostic accuracy or to compare their results with those of enzyme-linked immunosorbent assay (ELISA) kits (EP and EIA).
Sera were obtained from 213 hospital outpatients with dyspeptic symptoms. The serological results were compared with the result of the 13C-urea breath test (UBT) which seems to be reliable.
Of the 213 subjects, 154 were diagnosed as positive for H. pylori infection according to the UBT. The sensitivities and specificities of these tests were 97.4% and 76.3%, 98.1% and 78.0%, 99.4% and 74.6%, and 98.1% and 71.2% for the EP, LZ, EIA and LIA tests, respectively. When the 13 subjects whose seropositive results of the four kits were completely opposite to the negative results of the UBT were excluded, the specificities of evaluated kits were all higher than 90%. The concordance rate between the EP and EIA tests was 98.1% (Spearman's rank correlation coefficient = 0.83) and that between the LZ and LIA tests was 97.1% (correlation coefficient = 0.91). The LZ gave higher antibody titer value than EP (p < 0.0001, Z = 9.82; Wilcoxon signed-rank test), and EIA gave higher value than LIA (p < 0.0001, Z = 6.43; Wilcoxon signed-rank test).
The latex immunoassay method provided the same reliability to ELISA in terms of the diagnostic accuracy for current H. pylori infection, although we should take into account the titer value differences by each test method in practical use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Usual sleep duration has substantial heritability and is associated with various physical and psychiatric conditions as well as mortality. However, for its genetic locus, only PAX8 and VRK2 have been ...replicated in previous genome-wide association studies (GWAS). We conducted a GWAS meta-analysis of self-reported usual sleep duration using three population-based cohorts totaling 31 230 Japanese individuals. A genome-wide significant locus was identified at 12q24 (p-value < 5.0 × 10-8). Subsequently, a functional variant in the ALDH2 locus, rs671, was replicated in an independent sample of 5140 Japanese individuals (p-value = 0.004). The association signal, however, disappeared after adjusting for alcohol consumption, indicating the possibility that the rs671 genotype modifies sleep duration via alcohol consumption. This hypothesis explained a modest genetic correlation observed between sleep duration and alcohol consumption (rG = 0.23). A Mendelian randomization analysis using rs671 and other variants as instrumental variables confirmed this by showing a causal effect of alcohol consumption, but not of coffee consumption on sleep duration. Another genome-wide significant locus was identified at 5q33 after adjusting for drinking frequency. However, this locus was not replicated, nor was the PAX8 and VRK2. Our study has confirmed that a functional ALDH2 variant, rs671, most strongly influences on usual sleep duration possibly via alcohol consumption in the Japanese population, and presumably in East Asian populations. This highlights the importance of considering the involvement of alcohol consumption in future GWAS of usual sleep duration, even in non-East Asian populations, where rs671 is monomorphic.
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