Menopausal hormone therapy and risk of oesophageal adenocarcinoma in a population-based cohort study.

BACKGROUND: Oesophageal adenocarcinoma is characterised by a strong male predominance. We aimed to test the hypothesis that menopausal hormonal therapy decreases the risk of oesophageal adenocarcinoma. METHODS: This population-based cohort study included all women who used systemic menopausal hormonal therapy (exposed) in Sweden between 2005 and 2018. For each exposed participant, five randomly selected female age-matched non-users of menopausal hormonal therapy (unexposed) were included. Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, smoking-related diagnoses, Helicobacter pylori eradication, use of non-steroidal anti-inflammatory drugs/aspirin, use of statins and hysterectomy. RESULTS: The study included 296,964 users of menopausal hormonal therapy and 1,484,820 non-users. Ever-users of menopausal hormonal therapy had an overall decreased risk of oesophageal adenocarcinoma (HR 0.78, 95% CI 0.63-0.97), which remained unchanged after further adjustment for gastro-oesophageal reflux disease (HR 0.78, 95% CI 0.63-0.97) and obesity/diabetes (HR 0.79, 95% CI 0.63-0.98). Decreased HRs were indicated both in users of oestrogen only (HR 0.82, 95% CI 0.60-1.12) and oestrogen combined with progestogen (HR 0.75, 95% CI 0.56-1.00). The risk reduction was more pronounced in users younger than 60 years (HR 0.57, 95% CI 0.38-0.86). CONCLUSIONS: Menopausal hormone therapy in women may decrease the risk of oesophageal adenocarcinoma.

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site.

BACKGROUND: To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site. METHODS: A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed. RESULTS: The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82-1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80-1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39-0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37-0.65). CONCLUSION: Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.

Haemoglobin A1c and serum glucose levels and risk of gastric cancer: a systematic review and meta-analysis.

BACKGROUND: This systematic review and meta-analysis examined associations between serum levels of haemoglobin A1c (HbA1c) and glucose and the risk of gastric cancer. METHODS: MEDLINE, Embase, and Cochrane Library were searched for studies examining associations between serum levels of HbA1c or glucose and the risk of gastric cancer. Inclusion of studies, quality assessment, and data extraction were conducted independently by two authors. Pooled hazard ratios (HR) with 95% confidence intervals (CI) were synthesised using random-effects models. Cochran's Q test and I2 statistic were used to assess heterogeneity. RESULTS: Among 3473 identified studies, 12 were included. Of these, 5 studies examined HbA1c levels and 7 studies examined serum glucose levels. Serum HbA1c levels >6% were associated with an increased risk of gastric cancer (HR 1.36, 95% CI 1.06-1.74). When compared with the lowest glucose categories, the highest glucose categories were associated with a borderline increased risk of gastric cancer (HR 1.11, 95% CI 0.98-1.26). In subgroup analyses, studies that adjusted for Helicobacter pylori infection indicated stronger associations between elevated HbA1c levels and gastric cancer (HR 2.08, 95% CI 1.46-2.98) than those without such adjustment (HR 1.10, 95% CI 0.91-1.32). CONCLUSIONS: Long-standing poor glycaemic control may increase the risk of gastric cancer. REGISTRATION NUMBER: PROSPERO CRD42020157453.

Aspirin use in relation to long-term survival after gastrectomy for gastric adenocarcinoma.

BACKGROUND: Low-dose aspirin use may reduce cancer incidence and mortality, but its influence on gastric adenocarcinoma survival is unclear. This study aimed to assess whether aspirin use improves long-term survival following gastrectomy for gastric adenocarcinoma. METHODS: This population-based cohort study included almost all patients who underwent gastrectomy for gastric adenocarcinoma in Sweden from 2006 to 2015, with follow-up throughout 2020. Preoperative exposure to a daily low-dose (75-160 mg) aspirin for 1 (main exposure), 2 and 3 years and for 1 year after gastrectomy was examined in relation to 5-year all-cause mortality (primary outcome) and disease-specific mortality. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI), adjusted for age, sex, education, calendar year, comorbidity, statin use, tumour location, tumour stage, neoadjuvant chemotherapy, surgeon volume of gastrectomy and surgical radicality. RESULTS: Among 2025 patients, 545 (26.9%) used aspirin at the date of gastrectomy. Aspirin use within 1 year before surgery did not decrease the adjusted risk of 5-year all-cause mortality (HR = 0.98, 95% CI 0.85-1.13) or disease-specific mortality (HR = 1.00, 95% CI 0.86-1.17). Preoperative aspirin use for 2 years (HR = 0.98, 95% CI 0.84-1.15) or 3 years (HR = 0.94, 95% CI 0.79-1.12) did not decrease the risk of 5-year all-cause mortality. Patients remaining on aspirin during the first year after gastrectomy had a similar 5-year all-cause mortality as non-users of aspirin (HR = 1.01, 95% CI 0.82-1.25). CONCLUSIONS: Low-dose aspirin use might not improve long-term survival after gastrectomy for gastric adenocarcinoma and may thus not be a target for adjuvant therapy in this group of patients.

Prediagnostic circulating levels of sex hormones and survival in esophageal adenocarcinoma.

Sex hormonal differences may contribute to the strong male predominance in esophageal adenocarcinoma (EAC), but whether sex hormone levels influence survival in EAC is unstudied. Our study aimed to assess associations between prediagnostic sex hormone levels and survival in EAC. In a population-based cohort study, 244 male EAC patients from the Janus Serum Bank Cohort in Norway were followed up through 2018. Associations between prediagnostic serum levels of 12 sex hormone measures and disease-specific mortality were assessed using multivariable Cox regression, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, body mass index, tobacco smoking, physical activity and surgical resection. Higher levels of sex hormone-binding globulin (SHBG) indicated decreased disease-specific mortality (HR 0.68, 95% CI 0.44-1.07, highest vs lowest tertile). In stratified analyses by surgery, such associations remained in nonoperated patients (HR 0.58, 95% CI 0.35-0.96, highest vs lowest tertile), but not in operated patients. Higher levels of follicle-stimulating hormone (FSH) were associated with increased disease-specific mortality in an exposure-response pattern; HRs for the middle and highest tertiles vs the lowest tertile were 1.35 (95% CI 0.89-2.05) and 1.61 (95% CI 1.06-2.43), respectively. No clear associations were observed with serum levels of dehydroepiandrosterone sulfate, luteinizing hormone, prolactin, testosterone, 17-OH-progesterone, progesterone, estradiol, androstenedione, testosterone:estradiol ratio or free testosterone index. These findings suggest that higher endogenous levels of SHBG and lower levels of FSH may increase the survival in EAC. The other 10 examined sex hormone measures may not influence the survival.

Improved prognosis in gastric adenocarcinoma among metformin users in a population-based study.

BACKGROUND: Metformin may improve the prognosis in gastric adenocarcinoma, but the existing literature is limited and contradictory. METHODS: This was a Swedish population-based cohort study of diabetes patients who were diagnosed with gastric adenocarcinoma in 2005-2018 and followed up until December 2019. The data were retrieved from four national health data registries: Prescribed Drug Registry, Cancer Registry, Patient Registry and Cause of Death Registry. Associations between metformin use before the gastric adenocarcinoma diagnosis and the risk of disease-specific and all-cause mortality were assessed using multivariable Cox proportional hazard regression. The hazard ratios (HRs) and 95% confidence intervals (CIs) were adjusted for sex, age, calendar year, comorbidity, use of non-steroidal anti-inflammatory drugs or aspirin, and use of statins. RESULTS: Compared with non-users, metformin users had a decreased risk of disease-specific mortality (HR 0.79, 95% CI 0.67-0.93) and all-cause mortality (HR 0.78, 95% CI 0.68-0.90). The associations were seemingly stronger among patients of female sex (HR 0.66, 95% CI 0.49-0.89), patients with tumour stage III or IV (HR 0.71, 95% CI 0.58-0.88), and those with the least comorbidity (HR 0.71, 95% CI 0.57-0.89). CONCLUSIONS: Metformin use may improve survival in gastric adenocarcinoma among diabetes patients.

Prediction Model of Long-term Survival After Esophageal Cancer Surgery.

OBJECTIVE: We aimed to develop prediction models for estimating the long-term survival in patients who have undergone surgery for esophageal cancer. BACKGROUND: Few prediction models have been developed for the long-term survival in esophageal cancer patients. METHODS: This nationwide Swedish population-based cohort study included 1542 patients who survived for ≥90 days after esophageal cancer surgery between 1987 and 2010, with follow-up until 2016. Risk prediction models for 1-, 3-, and 5-year all-cause mortality and 3- and 5-year disease-specific mortality were developed using logistic regression. Candidate predictors were established and readily identifiable prognostic factors. The performance of the models was assessed by the area under receiver-operating characteristic curve (AUC) with interquartile range (IQR) using bootstrap cross-validation and risk calibration. RESULTS: Predictors included in all models were age, sex, pathological tumor stage, tumor histology, and resection margin status. The models also included various additional predictors depending on the outcome, that is, education level, neoadjuvant therapy, reoperation (within 30 d of primary surgery) and comorbidity (Charlson comorbidity index). The AUC statistics after cross-validation were 0.71 (IQR 0.69-0.74) for 1-year, 0.77 (IQR 0.75-0.80) for 3-year, and 0.78 (IQR 0.76-0.81) for 5-year all-cause mortality. The corresponding values were 0.76 (IQR 0.74-0.79) for 3-year and 0.77 (IQR 0.71-0.83) for 5-year disease-specific mortality. All models showed good agreement between the observed and predicted risks. CONCLUSIONS: These models showed good performance for predicting long-term survival after esophageal cancer surgery and may thus be useful for patients in planning their lives and to guide the postoperative treatment and follow-up.

Development and Validation of a Risk Prediction Model for Esophageal Squamous Cell Carcinoma Using Cohort Studies.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) carries a poor prognosis, but earlier tumor detection would improve survival. We aimed to develop and externally validate a risk prediction model based on exposure to readily available risk factors to identify high-risk individuals of ESCC. METHODS: Competing risk regression modeling was used to develop a risk prediction model. Individuals' absolute risk of ESCC during follow-up was computed with the cumulative incidence function. We used prospectively collected data from the Nord-Trøndelag Health Study (HUNT) for model derivation and the UK Biobank cohort for validation. Candidate predictors were age, sex, tobacco smoking, alcohol consumption, body mass index (BMI), education, cohabitation, physical exercise, and employment. Model performance was validated internally and externally by evaluating model discrimination using the area under the receiver-operating characteristic curve (AUC) and model calibration. RESULTS: The developed risk prediction model included age, sex, smoking, alcohol, and BMI. The AUC for 5-year risk of ESCC was 0.76 (95% confidence interval [CI], 0.58-0.93) in the derivation cohort and 0.70 (95% CI, 0.64-0.75) in the validation cohort. The calibration showed close agreement between the predicted cumulative risk and observed probabilities of developing ESCC. Higher net benefit was observed when applying the risk prediction model than considering all participants as being at high risk, indicating good clinical usefulness. A web tool for risk calculation was developed: https://sites.google.com/view/escc-ugis-ki. DISCUSSION: This ESCC risk prediction model showed good discrimination and calibration and validated well in an independent cohort. This readily available model can help select high-risk individuals for preventive interventions.

Causes of death in patients diagnosed with gastric adenocarcinoma in Sweden, 1970-2014: A population-based study.

The causes of death in patients with gastric adenocarcinoma have not been well characterized. This nationwide population-based cohort study included 56 240 patients diagnosed with gastric adenocarcinoma in 1970-2014 in Sweden. We used competing-risks regression to compare cause-specific risks of death in patients with different characteristics and a multiple-cause approach to assess proportions of deaths attributable to each cause. Among 53 049 deaths, gastric cancer was the main (77.7% of all deaths) underlying cause. Other major underlying causes were nongastric malignancies (8.0%), ischemic heart disease or cerebrovascular disease (6.5%), and respiratory diseases (1.4%). Risk of death from gastric cancer steadily decreased in patients with cardia adenocarcinoma over the study period, but remained relatively stable in patients with noncardia adenocarcinoma since the 1980s. Risk of death from other malignancies increased during later calendar periods (subhazard ratio [SHR] = 2.16, 95% confidence interval [CI] 1.97-2.38, comparing 2001-2014 with 1970-1980). Compared with men, the risk of death in women with cardia adenocarcinoma was higher from gastric cancer (SHR = 1.18, 95% CI 1.10-1.27), but lower from other malignancies (SHR = 0.80, 95% CI 0.71-0.91). In multiple-cause models, 60.4%-71.2% of all deaths were attributable to gastric cancer and 9.5%-12.1% to other malignancies. The temporal trends of cause-specific risks from multiple-cause models were similar to those of underlying causes. Our findings suggest that although most deaths in patients with gastric adenocarcinoma are due to gastric cancer, other causes of death are common. Patients with cardia adenocarcinoma face considerable increasing risk of death from other causes over time, particularly from other malignancies.

Information on Genetic Variants Does Not Increase Identification of Individuals at Risk of Esophageal Adenocarcinoma Compared to Clinical Risk Factors.

We previously developed a tool that identified individuals who later developed esophageal adenocarcinoma (based on age, sex, body mass index, smoking status, and prior esophageal conditions) with an area under the curve of 0.80. In this study, we collected data from 329,463 individuals in the UK Biobank cohort who were tested for genetic susceptibility to esophageal adenocarcinoma (a polygenic risk score based on 18 recognized genetic variants). We found that after inclusion of this genetic information, the area under the curve for identification of individuals who developed esophageal adenocarcinoma remained at 0.80. Testing for genetic variants associated with esophageal adenocarcinoma therefore seems unlikely to improve identification of individuals at risk of esophageal adenocarcinoma.

Association Between Levels of Sex Hormones and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.

BACKGROUND & AIMS: Esophageal adenocarcinoma (EAC) occurs most frequently in men. We performed a Mendelian randomization analysis to investigate whether genetic factors that regulate levels of sex hormones are associated with risk of EAC or Barrett's esophagus (BE). METHODS: We conducted a Mendelian randomization analysis using data from patients with EAC (n = 2488) or BE (n = 3247) and control participants (n = 2127), included in international consortia of genome-wide association studies in Australia, Europe, and North America. Genetic risk scores or single-nucleotide variants were used as instrumental variables for 9 specific sex hormones. Logistic regression provided odds ratios (ORs) with 95% CIs. RESULTS: Higher genetically predicted levels of follicle-stimulating hormones were associated with increased risks of EAC and/or BE in men (OR, 1.14 per allele increase; 95% CI, 1.01-1.27) and in women (OR, 1.28; 95% CI, 1.03-1.59). Higher predicted levels of luteinizing hormone were associated with a decreased risk of EAC in men (OR, 0.92 per SD increase; 95% CI, 0.87-0.99) and in women (OR, 0.93; 95% CI, 0.79-1.09), and decreased risks of BE (OR, 0.88; 95% CI, 0.77-0.99) and EAC and/or BE (OR, 0.89; 95% CI, 0.79-1.00) in women. We found no clear associations for other hormones studied, including sex hormone-binding globulin, dehydroepiandrosterone sulfate, testosterone, dihydrotestosterone, estradiol, progesterone, or free androgen index. CONCLUSIONS: In a Mendelian randomization analysis of data from patients with EAC or BE, we found an association between genetically predicted levels of follicle-stimulating and luteinizing hormones and risk of BE and EAC.

Association Between Metformin Use and Risk of Esophageal Squamous Cell Carcinoma in a Population-Based Cohort Study.

OBJECTIVES: Esophageal cancer is a highly fatal malignant neoplasm, with 2 etiologically different histological types. A large prospective study is expected to elucidate the specific risk of the 90% subtype of esophageal cancer, esophageal squamous cell carcinoma (ESCC), with metformin therapy. This study aims to determine the association between metformin use and incident ESCC risk. METHODS: This was a nationwide population-based prospective cohort study conducted in Sweden in 2005-2015. Among 8.4 million participants identified in the cohort, 411,603 (5%) were metformin users. The users were compared with 10 times as many frequency-matched nonusers of metformin (n = 4,116,030) by age and sex. Metformin use was treated as a time-varying variate, and multivariable cause-specific proportional hazards model was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for ESCC, adjusted for age, sex, calendar year, residence area, tobacco smoking, alcohol overconsumption, and use of nonsteroidal anti-inflammatory drugs or statins. RESULTS: The incidence rates of ESCC were 3.5 per 100,000 person-years among the metformin users and 5.3 per 100,000 person-years in the nonusers. Metformin users overall were at a decreased risk of ESCC compared with nonusers (HR 0.68, 95% CI 0.54-0.85). The decrease in risk was more pronounced in new metformin users (HR 0.44, 95% CI 0.28-0.64) and participants aged 60-69 years (HR 0.45, 95% CI 0.31-0.66). DISCUSSION: Metformin use decreases the risk of developing ESCC.

Circulating Sex Hormone Levels and Risk of Esophageal Adenocarcinoma in a Prospective Study in Men.

OBJECTIVES: Sex hormones have been hypothesized to explain the strong male predominance in esophageal adenocarcinoma, but evidence is needed. This study examined how circulating sex hormone levels influence future risk of esophageal adenocarcinoma. METHODS: This case-control study was nested in a prospective Norwegian cohort (Janus Serum Bank Cohort), including 244 male patients with esophageal adenocarcinoma and 244 male age-matched control participants. Associations between prediagnostic circulating levels of 12 sex hormones and risk of esophageal adenocarcinoma were assessed using conditional logistic regression. In addition, a random-effect meta-analysis combined these data with a similar prospective study for 5 sex hormones. RESULTS: Decreased odds ratios (ORs) of esophageal adenocarcinoma were found comparing the highest with lowest quartiles of testosterone (OR = 0.44, 95% confidence interval [CI] 0.22-0.88), testosterone:estradiol ratio (OR = 0.37, 95% CI 0.19-0.72), and luteinizing hormone (OR = 0.50, 95% CI 0.30-0.98), after adjustment for tobacco smoking and physical activity. These associations were attenuated after further adjustment for body mass index (OR = 0.56, 95% CI 0.27-1.13 for testosterone; OR = 0.46, 95% CI 0.23-0.91 for testosterone:estradiol ratio; OR = 0.55, 95% CI 0.29-1.08 for luteinizing hormone). No associations were observed for sex hormone-binding globulin, dehydroepiandrosterone sulfate, follicle-stimulating hormone, prolactin, 17-OH progesterone, progesterone, androstenedione, or free testosterone index. The meta-analysis showed an inverse association between testosterone levels and risk of esophageal adenocarcinoma (pooled OR for the highest vs lowest quartile = 0.60, 95% CI 0.38-0.97), whereas no associations were identified for androstenedione, sex hormone-binding globulin, estradiol, or testosterone:estradiol ratio. DISCUSSION: Higher circulating testosterone levels may decrease the risk of esophageal adenocarcinoma in men.

Geographical variations in the incidence of oesophageal cancer in Sweden.

Background: Geographical variations in the incidence and tumour stage distribution of oesophageal cancer in Sweden are not well characterised.Methods: Using data from the Swedish Cancer Registry over 45 years (1972-2016), we compared the age-standardised incidence rates of oesophageal cancer by histological type across all seven national areas (in five-year periods) and 21 counties (in 15-year periods) in Sweden, and assessed the geographical distribution of tumour stage at diagnosis since 2004.Results: The incidence rate of oesophageal adenocarcinoma increased in all national areas and counties and in both sexes over time, while the rate of oesophageal squamous cell carcinoma decreased from the 1980s onwards. In the latest period (2012- 2016), the incidence rate of adenocarcinoma in men ranged from 3.5/100,000 person-years in West Sweden to 6.2/100,000 person-years in North Middle Sweden. At the county level, the rate of adenocarcinoma in men was lowest in Jämtland (2.7/100,000 person-years) and highest in Gotland (6.2/100 000 person-years) in 2002-2016. The incidence rates of both adenocarcinoma and squamous cell carcinoma in women were below 2/100,000 person-years in all national areas and counties in the latest calendar periods, i.e., 2012-2016 and 2002-2016, respectively. The proportion of patents with tumour stage IV ranged from 22% in Stockholm area to 31% in Middle Norrland, while at the healthcare region level it was lowest in Stockholm healthcare region (23%) and highest in North (30%) and Uppsala-Örebro (29%) healthcare regions.Conclusion: There are considerable geographical variations in the incidence and tumour stage distribution of oesophageal cancer in Sweden.

Sex difference in the incidence of cardia and non-cardia gastric cancer in the United States, 1992-2014.

BACKGROUND: Gastric cancer is more common in men than in women, but underlying reasons have not been completely understood. This study aimed to assess patterns of the sex difference in the incidence of gastric cancer in the United States. METHODS: Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results Program, we analyzed the age-specific sex difference in the incidence of gastric cancer by ethnicity, anatomic site and histological type in the United States during 1992-2014. We assessed the temporal trends in the sex differences in the incidence of gastric cancer during the study period. RESULTS: The male-to-female incidence ratio of cardia cancer increased with age until peaking at ages 55-69 years and decreased thereafter, while the ratio for non-cardia gastric cancer increased with age before ages < 60 years and remained stable onwards. The age-specific patterns in the sex difference of gastric cancer incidence varied between intestinal and diffuse histological types. The sex difference in the incidence of cardia cancer remained relatively stable except for that the absolute difference between the sexes in whites decreased on average by 0.8% per year from 1992 to 2014. The absolute incidence difference between the sexes in non-cardia gastric cancer decreased over time in whites, blacks, and Asian and Pacific islanders by approximately 4% per year. The male-to-female incidence ratio of non-cardia gastric cancer decreased over time in whites and blacks, but remained relatively stable in Asian and Pacific islanders. CONCLUSIONS: Both extrinsic and intrinsic factors may have contributed to the sex difference in gastric cancer. Sex hormones may play a role in the development of cardia cancer and intestinal type of gastric cancer.

Efficient Hydrogen Production from Methanol Using a Single-Site Pt1/CeO2 Catalyst.

Hydrogen is regarded as an attractive alternative energy carrier due to its high gravimetric energy density and only water production upon combustion. However, due to its low volumetric energy density, there are still some challenges in practical hydrogen storage and transportation. In the past decade, using chemical bonds of liquid organic molecules as hydrogen carriers to generate hydrogen in situ provided a feasible method to potentially solve this problem. Research efforts on liquid organic hydrogen carriers (LOHCs) seek practical carrier systems and advanced catalytic materials that have the potential to reduce costs, increase reaction rate, and provide a more efficient catalytic hydrogen generation/storage process. In this work, we used methanol as a hydrogen carrier to release hydrogen in situ with the single-site Pt1/CeO2 catalyst. Moreover, in this reaction, compared with traditional nanoparticle catalysts, the single site catalyst displays excellent hydrogen generation efficiency, 40 times higher than 2.5 nm Pt/CeO2 sample, and 800 times higher compared to 7.0 nm Pt/CeO2 sample. This in-depth study highlights the benefits of single-site catalysts and paves the way for further rational design of highly efficient catalysts for sustainable energy storage applications.

Metformin use and risk of gastric adenocarcinoma in a Swedish population-based cohort study.

BACKGROUND: Whether or not the use of metformin decreases the risk of gastric adenocarcinoma is unclear. METHODS: This was a population-based cohort study in 2005-2015. Associations between metformin use and gastric non-cardia and cardia adenocarcinomas were examined within two cohorts; a diabetes cohort of participants using anti-diabetes medications, and a matched cohort of common-medication users, where metformin non-users were frequency matched (10:1) with metformin users for sex and age. Multivariable Cox proportional hazard regression analyses provided hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, calendar year, comorbidity, Helicobacter pylori eradication treatment, use of non-steroidal anti-inflammatory drugs or aspirin and use of statins. RESULTS: During the follow-up for a median of 5.8 years, 892 (0.1%) participants in the diabetes cohort and 6395 (0.1%) participants in the matched cohort of common-medication users developed gastric adenocarcinoma. Metformin users had no significantly decreased risk of gastric non-cardia adenocarcinoma (diabetes cohort: HR 0.93, 95% CI 0.78-1.12; matched cohort: HR 1.30, 95% CI 1.18-1.42) or cardia adenocarcinoma (diabetes cohort: HR 1.49, 95% CI 1.09-2.02; matched cohort: HR 1.58, 95% CI 1.38-1.81) compared with non-users in both cohorts. CONCLUSIONS: This cohort study with <10 years of follow-up suggests metformin use may not prevent gastric adenocarcinoma.

Prediabetes and diabetes in relation to risk of gastric adenocarcinoma.

BACKGROUND: Whether prediabetes or diabetes increases the risk of gastric adenocarcinoma is not clear. METHODS: This cohort study included 111,198 participants in the Northern Swedish Health and Disease Study. The participants were followed up from November 1985 to April 2017. The exposure to prediabetes or diabetes was assessed by oral glucose tolerance tests and self-reports. The incidence of the outcome gastric adenocarcinoma was identified from the Swedish Cancer Registry. Multivariable Cox regressions were used to analyse the associations between prediabetes or diabetes and the risk of gastric adenocarcinoma, providing hazard ratios (HR) with 95% confidence intervals (CI), with adjustment for sex, age, calendar year, body mass index, tobacco smoking and education level. RESULTS: Compared with normoglycaemic participants, the risk of gastric adenocarcinoma was not increased among participants with prediabetes (HR 1.07, 95% CI 0.79-1.44), diabetes (HR 0.77, 95% CI 0.46-1.29) or any of these exposures (HR 0.96, 95% CI 0.73-1.27). No associations were identified between prediabetes or diabetes and the risk of gastric adenocarcinoma in stratified analyses or in analyses separating cardia and non-cardia gastric adenocarcinoma. CONCLUSIONS: This study does not support the hypothesis that prediabetes or diabetes increases the risk of gastric adenocarcinoma.

The Epidemiology of Esophageal Adenocarcinoma.

The incidence of esophageal adenocarcinoma (EAC) has increased in many Western countries and is higher in men than women. Some risk factors for EAC have been identified-mainly gastroesophageal reflux disease, Barrett's esophagus, obesity, and tobacco smoking. It is not clear whether interventions to address these factors can reduce risk of EAC, although some evidence exists for smoking cessation. Although consumption of alcohol is not associated with EAC risk, other exposures, such as physical activity, nutrition, and medication use, require further study. Genetic variants have been associated with risk for EAC, but their overall contribution is low. Studies are needed to investigate associations between risk factors and the molecular subtypes of EAC. The prognosis for patients with EAC has slightly improved, but remains poor-screening and surveillance trials of high-risk individuals are needed.

Prediction of individuals at high absolute risk of esophageal squamous cell carcinoma.

BACKGROUND AND AIMS: This study aimed to develop a prediction model for identifying individuals at high absolute risk of esophageal squamous cell carcinoma (ESCC) for endoscopic screening at a curable stage based on readily identifiable risk factors. METHODS: This was a nationwide Swedish population-based, case-control study, including 167 new cases of ESCC and 820 randomly selected control participants. Odds ratios with 95% confidence intervals (CI) were assessed by using multivariable unconditional logistic regression. The discriminative accuracy of the model was assessed by the area under the receiver operating characteristic curve (AUC) with leave-1-out cross validation. Models for projecting individuals' absolute 5-year risk of ESCC were developed by incorporating the age-specific and sex-specific incidence rates and competing risk of death from other causes. RESULTS: A model including the risk factors age, sex, tobacco smoking, alcohol overconsumption, education, duration of living with a partner, and place of residence during childhood generated an AUC of 0.81 (95% CI, 0.77-0.84). A model based only on age, sex, tobacco smoking, and alcohol overconsumption obtained a similar AUC (0.79; 95% CI, 0.75-0.82). A 5-year follow-up of 355 men aged 70 to 74 years with over 35 years' smoking and alcohol overconsumption history is needed to detect 1 ESCC case. The estimated individuals' absolute 5-year risk of ESCC varied according to the combinations of risk factors. CONCLUSION: This easy-to-use risk prediction model showed a good discriminative accuracy and had the potential to identify individuals at high absolute risk of ESCC who might benefit from tailored endoscopic screening and surveillance.