Takahiro Otani

Background: The aldehyde dehydrogenase 2 (ALDH2) rs671 (G>A) variant, common in East Asians, impairs aldehyde detoxification. Pathogenic germline variants (PGVs) in homologous recombination repair (HRR) and mismatch repair (MMR) genes confer inherited susceptibility; however, their joint effects with rs671 remain poorly characterized. Methods: We conducted a case-control study of 4,418 cases of head and neck, esophageal, gastric, or colorectal cancer and 11,811 controls. Targeted sequencing identified HRR and MMR PGVs. Associations and interactions were assessed using Firth-penalized logistic regression, stratified by alcohol intake. Cumulative risk was estimated using Japanese population incidence data. Results: HRR PGV carriers with the rs671 GA/AA genotype showed increased risk across all cancer sites compared with rs671 GG non-carriers. Joint effects were observed among drinkers for head and neck, esophageal, and gastric cancers, and among non-drinkers for gastric and colorectal cancers. Among MMR PGV carriers, rs671 GA/AA was associated with increased risk of esophageal and colorectal cancers (odds ratio, 95.62 and 24.57, respectively), with significant interactions (P = 0.017 and 0.0011, respectively). The rs671–MMR association for esophageal cancer was evident among drinkers, whereas colorectal cancer risk was elevated in both drinkers and non-drinkers. By age 80, cumulative risk (95% confidence interval) among MMR PGV carriers with rs671 GA/AA was 35.4% (7.7–90.3) for esophageal and 87.7% (46.9–99.9) for colorectal cancer. Conclusions: Impaired aldehyde detoxification and DNA repair deficiency jointly increase site-specific cancer risk. Impact: Integrating ALDH2 rs671 genotype, DNA repair PGVs, and alcohol exposure may improve risk stratification and prevention in East Asian populations.

Detecting multiple disease clusters using the information criterion and scan statistic approach developed by Takahashi and Shimadzu (2020) .

BACKGROUNND: We investigated the characteristic variables of acute ischemic stroke categorized according to body mass index (BMI). METHODS: From a registry of 1676 consecutive acute ischemic stroke cases, 965 cases (622 men and 434 women; mean age 71.53 ± 12.42 years) were selected based on eligibility criteria. These participants were divided into four cohorts according to BMI classifications: BMI < 18 (underweight), 18.5 ≤ BMI < 25 (normal weight), 25 ≤ BMI < 30 (overweight), and BMI ≥ 30 (obese). To avoid bias, propensity score analyses were performed; the confounding variables of sex and age were adjusted. RESULTS: The underweight cohort (n = 82) had an older, largely female population. The overweight (n = 212) and obese cohorts (n = 48) had younger populations. The analyses revealed no significant differences in neurological outcomes among the four cohorts. Furthermore, higher risks of hyperlipidemia, dyslipidemia, and diabetes mellitus were associated with the higher BMI cohorts in participants with acute ischemic stroke. Findings revealed higher rates of usage of antidiabetic and antidyslipidemic medications in the overweight cohort (p = 0.007, p = 0.003; respectively) and raised values of triglycerides, low-density lipoprotein cholesterol, and glycated hemoglobin in the obese cohort (p = 0.044, p = 0.019, p < 0.001; respectively) than in the normal weight cohort. By contrast, the lower BMI cohort (underweight) did not have hyperlipidemia. CONCLUSIONS: The importance of focusing on the management of dyslipidemia, hyperlipidemia, and hyperglycemia for acute ischemic stroke in patients who are overweight or obese has been highlighted.

Aspirin has been shown to prevent the onset of colorectal adenoma and cancer. This study aimed to identify patient characteristics and blood chemistry factors related to the effect of aspirin. A total of 231 men and 59 women who participated in our previous randomized clinical study in 2007–2009 using aspirin or placebo (J-CAPP study) were analyzed. Interaction of aspirin with age at entry, body mass index (BMI), alcohol intake, blood biochemistry, and nutrients calculated from a semiquantitative food frequency questionnaire were analyzed on the basis of the presence of adenomas 2 years later. Our study showed that suppression of adenoma by aspirin was not affected by age or BMI. Among men, significant suppression of adenoma by aspirin was seen with triglyceride (TG) <167 mg/dL (P = 0.02), total cholesterol (T-cho) ≥220 mg/dL (P = 0.01), high-density lipoprotein (HDL) ≥60 mg/dL (P < 0.01), and low-density lipoprotein (LDL) ≥140 mg/dL (P = 0.01), aspartate aminotransferase (AST) <30 IU/L (P = 0.01), alanine aminotransferase <30 IU/L (P = 0.04), and gamma-glutamyl transpeptidase <60 IU/L (P = 0.04). In addition, the interaction was significant with TG ≥/<167 mg/dL (P = 0.02), T-cho ≥/<220 mg/dL (P = 0.03), HDL ≥/<60 mg/dL (P = 0.02), LDL ≥/<140 mg/dL (P = 0.03), and AST ≥/<30 IU/L (P = 0.01). Daily nutrient intake associated with aspirin was <2,000 mg sodium (P = 0.06) and ≥850 μg retinol equivalent (P = 0.05) among men, indicating a marginal effect on adenoma suppression. No significant differences were detected among women due to the small sample size. In conclusion, lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma.Prevention Relevance:Aspirin has been shown to prevent the onset of colorectal adenoma and cancer, and its effect modifications have been analyzed. Lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma.

Supplementary Table from Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake

Supplementary Figure from Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake

Supplementary Table from Aspirin-Mediated Prevention of Colorectal Adenomas Recurrence is Affected by Blood Biochemistry and Nutritional Intake

Aspirin has been shown to prevent the onset of colorectal adenoma and cancer. This study aimed to identify patient characteristics and blood chemistry factors related to the effect of aspirin. A total of 231 men and 59 women who participated in our previous randomized clinical study in 2007–2009 using aspirin or placebo (J-CAPP study) were analyzed. Interaction of aspirin with age at entry, body mass index (BMI), alcohol intake, blood biochemistry, and nutrients calculated from a semiquantitative food frequency questionnaire were analyzed on the basis of the presence of adenomas 2 years later. Our study showed that suppression of adenoma by aspirin was not affected by age or BMI. Among men, significant suppression of adenoma by aspirin was seen with triglyceride (TG) <167 mg/dL (P = 0.02), total cholesterol (T-cho) ≥220 mg/dL (P = 0.01), high-density lipoprotein (HDL) ≥60 mg/dL (P < 0.01), and low-density lipoprotein (LDL) ≥140 mg/dL (P = 0.01), aspartate aminotransferase (AST) <30 IU/L (P = 0.01), alanine aminotransferase <30 IU/L (P = 0.04), and gamma-glutamyl transpeptidase <60 IU/L (P = 0.04). In addition, the interaction was significant with TG ≥/<167 mg/dL (P = 0.02), T-cho ≥/<220 mg/dL (P = 0.03), HDL ≥/<60 mg/dL (P = 0.02), LDL ≥/<140 mg/dL (P = 0.03), and AST ≥/<30 IU/L (P = 0.01). Daily nutrient intake associated with aspirin was <2,000 mg sodium (P = 0.06) and ≥850 μg retinol equivalent (P = 0.05) among men, indicating a marginal effect on adenoma suppression. No significant differences were detected among women due to the small sample size. In conclusion, lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma.Prevention Relevance:Aspirin has been shown to prevent the onset of colorectal adenoma and cancer, and its effect modifications have been analyzed. Lipid metabolism and liver function were correlated with the suppressive effect of aspirin on the recurrence of colorectal adenoma.