Background
Aldehyde dehydrogenase 2 (
ALDH2
; rs671, Glu504Lys) and alcohol dehydrogenase 1B (
ADH1B
; rs1229984, His47Arg) polymorphisms have a strong impact on carcinogenic acetaldehyde ...accumulation after alcohol drinking. To date, however, evidence for a significant
ALDH2
–alcohol drinking interaction and a mediation effect of
ALDH2
/
ADH1B
through alcohol drinking on gastric cancer have remained unclear. We conducted two case–control studies to validate the interaction and to estimate the mediation effect on gastric cancer.
Methods
We calculated odds ratios (OR) and 95% confidence intervals (CI) for
ALDH2
/
ADH1B
genotypes and alcohol drinking using conditional logistic regression models after adjustment for potential confounding in the HERPACC-2 (697 cases and 1372 controls) and HERPACC-3 studies (678 cases and 678 controls). We also conducted a mediation analysis of the combination of the two studies to assess whether the effects of these polymorphisms operated through alcohol drinking or through other pathways.
Results
ALDH2
Lys alleles had a higher risk with increased alcohol consumption compared with
ALDH2
Glu/Glu (OR for heavy drinking, 3.57; 95% CI 2.04–6.27;
P
for trend = 0.007), indicating a significant
ALDH2
–alcohol drinking interaction (
P
interaction
= 0.024). The mediation analysis indicated a significant positive direct effect (OR 1.67; 95% CI 1.38–2.03) and a protective indirect effect (OR 0.84; 95% CI 0.76–0.92) of the
ALDH2
Lys alleles with the
ALDH2
–alcohol drinking interaction. No significant association of
ADH1B
with gastric cancer was observed.
Conclusion
The observed
ALDH2
–alcohol drinking interaction and the direct effect of
ALDH2
Lys alleles may suggest the involvement of acetaldehyde in the development of gastric cancer.
Background: Although cigarette smoking is an established risk factor for bladder cancer, assessment of smoking impact on bladder cancer in Asian populations has been hindered by few cohort studies ...conducted in Asian populations. Therefore, we investigated the risk of bladder cancer associated with smoking status, cumulative smoking intensity, and smoking cessation in Japan.Methods: We analyzed data for 157,295 men and 183,202 women in 10 population-based cohort studies in Japan. The risk associated with smoking behaviors was estimated using Cox regression models within each study, and pooled hazard ratios (HRs) and their 95% confidence intervals (CIs) for the incidence of bladder cancer were calculated.Results: During 4,729,073 person-years of follow-up, 936 men and 325 women developed bladder cancer. In men, former smokers (HR 1.47; 95% CI, 1.18–1.82) and current smokers (HR 1.96; 95% CI, 1.62–2.38) had higher risk than never smokers. In women, current smokers had higher risk than never smokers (HR 2.35; 95% CI, 1.67–3.32). HRs in men linearly increased with increasing pack-years. Risk decreased with increasing years of smoking cessation in men, with a significant dose-response trend. Former smokers with a duration of more than 10 years after smoking cessation had no significantly increased risk compared with never smokers (HR 1.26; 95% CI, 0.97–1.63).Conclusion: Data from a pooled analysis of 10 population-based cohort studies in Japan clearly show an association between cigarette smoking and bladder cancer risk. The risk of smokers may approximate that of never smokers following cessation for many years.
The association of alcohol drinking with bladder cancer risk remains unclear in East Asian populations. Aldehyde dehydrogenase 2 (ALDH2) enzyme oxidizes alcohol-metabolized carcinogenic acetaldehyde ...into acetate. It is well known that the inactive ALDH2 carriers, specific to East Asian populations, have an increased risk of several cancer types because of increased exposure to acetaldehyde after alcohol consumption. The aim of this study was to examine the association between alcohol drinking and bladder cancer risk using data from ten population-based prospective cohort studies in Japan, where approximately 40% of the population has inactive ALDH2 enzyme.
We analyzed 340,497 Japanese participants with average follow-up of 13.4 years. The association between alcohol drinking and bladder cancer risk was evaluated using Cox regression models within each study, and random-effects models were used to estimate pooled hazard ratios (HRs) with corresponding 95% confidence intervals (CIs).
During 4,729,071 person-years, 936 men and 325 women were newly diagnosed with bladder cancer. Our results showed no evidence of significant association between alcohol drinking and bladder cancer risk even among men who consumed alcohol of ≥69 g/week, with HR of 1.02 (95% CI, 0.79-1.33). The null result was observed consistently among women.
Our findings do not support an association between alcohol drinking and bladder cancer risk in the Japanese, at least without consideration of the polymorphisms of alcohol-metabolizing enzymes.
Despite treatment guidelines recommending observation for men with low‐risk prostate cancer with life expectancy <10 years, a majority of elderly patients choose active treatment, which may result in ...overtreatment. Given the growing burden of prostate cancer among men aged ≥80 years (super‐elderly men), accumulation of survival data for evaluation of overtreatment among super‐elderly patients is imperative. Here, we report results of a population‐based cohort study to clarify potential overtreatment of super‐elderly men with localized prostate cancer. We used cancer registry data from the Monitoring of Cancer Incidence in Japan project, which covers 47% of the Japanese population. The subjects were men diagnosed with prostate cancer between 2006 and 2008. Follow‐up period was 5 years. We calculated 5‐year relative survival rates among the active treatment and observation groups after imputation for missing values. Of the 48 782 patients with prostate cancer included in the analysis, 15.1% were super‐elderly men. The 5‐year relative survival rates of super‐elderly men with localized cancer were 105.9% and 104.1% among the active treatment and observation groups, respectively. This excellent relative survival rate in the observation group remained consistent even after stratification by tumor grade. Of the 2963 super‐elderly men with localized cancer, 252 (8.5%) with curative treatment and 1476 (49.8%) with hormone therapy were assumed to have been overtreated. The proportion of overtreatment was estimated to reach 80% after imputation. These specific survival data in super‐elderly men in the observation group can be useful in shared decision‐making for these patients and may lead to a reduction in overtreatment.
Data from a Japanese large‐scale population‐based cancer registry showed that men aged 80 years and older (super‐elderly men) with localized prostate cancer in the observation group had an excellent survival outcome. Our findings suggest that more than half of super‐elderly men with localized prostate cancer are overtreated in Japan. Accumulation of evidence based on survival data of super‐elderly men in the observation group may promote shared decision‐making for these patients, leading to a reduction in overtreatment.
Subtype of urothelial carcinoma (SUC), defined here as urothelial carcinoma with any histologic subtype or divergent differentiation, is a clinically aggressive disease. However, the efficacy of ...enfortumab vedotin (EV) against SUC remains unclear. Hence, this study aimed to assess the oncological outcomes of patients with SUC treated with EV for metastatic disease. We retrospectively evaluated consecutive patients with advanced lower and upper urinary tract cancer who received EV after platinum-based chemotherapy and immune checkpoint blockade therapy at six institutions. The objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) were compared between patients with pure urothelial carcinoma (PUC) and those with SUC. We identified 44 and 18 patients with PUC and SUC, respectively. Squamous differentiation was the most common subtype element, followed by glandular differentiation and sarcomatoid subtype. Although patients with SUC had a comparable ORR to those with PUC, the duration of response for SUC was short. Patients with SUC had poorer PFS than those with PUC; however, no significant difference was observed in OS. Multivariate analysis revealed that SUC was significantly associated with shorter PFS. Although the response of metastatic SUC to EV was similar to that of PUC, SUC showed faster progression than PUC.
Although several epidemiological studies have demonstrated that cigarette smoking is an important risk factor for bladder cancer, no systematic review in the Japanese population has yet been ...performed. Accurate evaluation of bladder cancer risk in relation to smoking for Japanese populations can provide necessary information for Japanese policy-makers and doctors to enlighten the importance of smoking cessation. We reviewed epidemiologic data to estimate the strength of the association between cigarette smoking and bladder cancer in the Japanese population.
We identified previous cohort and case-control studies, extracting data from databases in the MEDLINE (PubMed) and Ichushi. The magnitude of association and strength of evidence were evaluated in each study, and a meta-analysis was conducted to obtain summary estimates for the overall magnitude of association.
Three cohort and eight case-control studies were identified. Except for one case-control study, all studies showed a strong positive association between cigarette smoking and bladder cancer. The summary relative risk for ever smokers relative to never smokers was 2.14 (95% confidence interval 1.87-2.44) in a fixed-effect model.
We conclude that cigarette smoking is a convincing risk factor for bladder cancer among Japanese.
To evaluate the relationship between body composition and the oncological outcome of androgen deprivation therapy (ADT), we investigated whether body composition features including the psoas muscle ...may be predictive factors of ADT.
This study enrolled patients with hormone-naïve metastatic prostate cancer who were treated with primary ADT from April 1996 to November 2013 at Kyushu University Hospital and who underwent a computed tomography scan before primary ADT for calculating body fat percentage, psoas muscle ratio (psoas muscle, cm3/height, cm), and body mass index.
Of the 178 patients enrolled, 60 patients died during follow-up. Median follow-up was 32 months, and progression-free survival and overall survival (OS) were 28 and 80 months, respectively. Multivariate analysis revealed that the psoas muscle ratio was correlated with OS (hazard ratio: 0.448; 95% confidence interval = 0.206–0.922; p = 0.028).
This study demonstrated that higher psoas muscle ratio predicts longer OS among patients with nonlocalized prostate cancer treated with primary ADT.
Traumatic hematomas in the posterior fossa are rare, especially traumatic posterior fossa subdural hematomas (SDHs), which account for <1% of head injured patients. The aim of this study was to ...investigate the features of traumatic posterior fossa SDHs.
We retrospectively reviewed clinical and radiologic findings, management, and outcomes of patients with traumatic posterior fossa SDH.
Ten patients with traumatic posterior fossa SDHs were admitted to our hospital. There were seven males and three females, with an age range of 3 years to 97 years (mean, 57.5 years). Coagulopathies were observed in five patients. The causes of injury were motor vehicle crash in three patients, falls in six patients, and being hit by an iron plate in one patient. The mean admission Glasgow Coma Scale score was 8.3. Skull fractures were revealed in six patients. Hematoma sizes ranged from 5 mm to 20 mm (mean, 7.7 mm). Two patients presented with isolated posterior fossa SDHs, and eight patients presented with associated intracranial lesions. Only one patient was treated surgically for posterior fossa SDHs associated with intracerebellar hematomas. The poor outcome rate was 90% and the mortality was 50%.
A review of the literature revealed the following characteristics of posterior fossa SDHs: (1) a relatively high frequency of occipital impacts and fractures, (2) a low Glasgow Coma Scale score, (3) a high frequency of associated intracranial lesions, especially supratentorial lesions and intracerebellar hematomas, (4) a potential for lesion evolution, especially within 2 days, and (5) a high poor outcome rate and mortality.
IV.
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