In February 2013, Japan became the first country in the world to cover Helicobacter pylori eradication for chronic gastritis under its National Health Insurance (NHI) system. Now that eradication ...therapy is covered by NHI, its usage has increased dramatically, and gastric cancer deaths have begun to decrease. We undertook a detailed epidemiological analysis to investigate effects of expanded NHI coverage for H. pylori eradication therapy on gastric cancer deaths in specific age groups. Numbers of gastric cancer deaths were determined by referencing data from Ministry of Health, Labour and Welfare reports and “Cancer Statistics in Japan – 2018” published by the Foundation for Promotion of Cancer Research. Gastric cancer deaths across all age groups have been clearly decreasing since 2013, but deaths of people aged 80 years and older are still increasing. The number of gastric cancer deaths in people aged in their 80s was 2 times higher than in people aged in their 70s and 4 times higher than in people aged in their 60s. The number of people in their 80s who had an endoscopy was less than half that of people in their 60s and 70s. The eradication therapy has increased dramatically, and gastric cancer deaths are clearly decreasing in Japan. However, this decrease in deaths has not extended to elderly adults aged in their 80s, which suggests that measures to prevent gastric cancer in people aged 80 years and older will be critical to achieving the mission of eliminating gastric cancer in Japan.
Japan became the first country to cover H. pylori eradication for chronic gastritis under its insurance system. The eradication therapy has increased dramatically, and gastric cancer deaths are clearly decreasing.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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
Abstract
Background
Pancreatic cancer treatment is evolving, but few studies have examined a nationwide trend in the treatment patterns. The purpose of this study was to clarify real-world treatment ...patterns for pancreatic cancer in Japan.
Methods
This retrospective study examined the treatment patterns among 68 479 patients, who had pancreatic cancer diagnosis in Medical Data Vision claims database from 2010 to 2018. We extracted relevant data on treatment options, including chemotherapy, surgery and their combination. For patients who had undergone chemotherapy, we sought to analyse the use of different chemotherapy regimens. In addition, we examined the trend in treatment patterns by age group (<59, 60–69, 70–79, ≥80).
Results
The trend in treatment options of pancreatic cancer remained stable from 2010 to 2018, with chemotherapy being the most common therapeutic option and surgery performed in approximately half that of chemotherapy. On the other hand, the use of chemotherapy regimen had changed during the same period. Although gemcitabine was the most commonly administrated single-agent regimen in 2010, gemcitabine + nab-paclitaxel was the most frequently used therapeutic agent in 2018. In the older age groups (age ≥80), the majority of patients was untreated (supposedly received supportive care), and the use of conventional regimens such as gemcitabine or S-1 was common among those undergoing chemotherapy.
Conclusions
Although chemotherapy has been the main treatment option for pancreatic cancer, the regimens of choice have increased significantly during the last decade. With accumulating evidence on combination chemotherapy, treatment options may further evolve in the future.
Based on a medical claims database, we analysed treatment patterns for pancreatic cancer in Japan, showing a significant change in the chemotherapy treatment options during the last decade.
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
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.
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.
Gout is a common disease resulting from hyperuricemia. Recently, a genome-wide association study identified an association between gout and a single nucleotide polymorphism (SNP) rs2188380, located ...on an intergenic region between MYL2 and CUX2 on chromosome 12. However, other genes around rs2188380 could possibly be gout susceptibility genes. Therefore, we performed a fine-mapping study of the MYL2-CUX2 region. From 8,595 SNPs in the MYL2-CUX2 region, 9 tag SNPs were selected, and genotyping of 1,048 male gout patients and 1,334 male controls was performed by TaqMan method. Eight SNPs showed significant associations with gout after Bonferroni correction. rs671 (Glu504Lys) of ALDH2 had the most significant association with gout (P = 1.7 × 10(-18), odds ratio = 0.53). After adjustment for rs671, the other 8 SNPs no longer showed a significant association with gout, while the significant association of rs671 remained. rs671 has been reportedly associated with alcohol drinking behavior, and it is well-known that alcohol drinking elevates serum uric acid levels. These data suggest that rs671, a common functional SNP of ALDH2, is a genuine gout-associated SNP in the MYL2-CUX2 locus and that "A" allele (Lys) of rs671 plays a protective role in the development of gout.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Gout/hyperuricemia is a common multifactorial disease having typical environmental risks. Recently, common dysfunctional variants of ABCG2, a urate exporter gene also known as BCRP, are revealed to ...be a major cause of gout/hyperuricemia. Here, we compared the influence of ABCG2 dysfunction on serum uric acid (SUA) levels with other typical risk factors in a cohort of 5,005 Japanese participants. ABCG2 dysfunction was observed in 53.3% of the population investigated, and its population-attributable risk percent (PAR%) for hyperuricemia was 29.2%, much higher than those of the other typical environmental risks, i.e. overweight/obesity (BMI ≥ 25.0; PAR% = 18.7%), heavy drinking (>196 g/week (male) or >98 g/week (female) of pure alcohol; PAR% = 15.4%), and aging (≥60 years old; PAR% = 5.74%). SUA significantly increased as the ABCG2 function decreased (P = 5.99 × 10(-19)). A regression analysis revealed that ABCG2 dysfunction had a stronger effect than other factors; a 25% decrease in ABCG2 function was equivalent to "an increase of BMI by 1.97-point" or "552.1 g/week alcohol intake as pure ethanol" in terms of ability to increase SUA. Therefore, ABCG2 dysfunction originating from common genetic variants has a much stronger impact on the progression of hyperuricemia than other familiar risks. Our study provides a better understanding of common genetic factors for common diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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