Andrew D. Spence

Adenocarcinoma risk in gastric atrophy and intestinal metaplasia: a systematic review

BackgroundGastric cancer (GC) has a poor prognosis with wide variation in survival rates across the world. Several studies have shown premalignant lesions gastric atrophy (GA) and intestinal metaplasia (IM) influence gastric cancer risk. This systematic review examines all available evidence of the risk of GC in patients with GA or IM and explores the geographical variation between countries.MethodsEMBASE, MEDLINE, Web of Science and the Cochrane Library were searched for relevant articles published to June 2016 investigating the risk of GC in individuals with GA or IM. Analysis was performed to determine variation based on geographical location. Study quality was assessed using the Newcastle-Ottawa Scale and heterogeneity between studies was also evaluated.ResultsFifteen relevant articles were identified, in which there were eight studies of GC incidence in GA and nine in IM cohorts (two articles investigated both GA and IM). The incidence rate of GC in patients with GA ranged from 0.53 to 15.24 per 1000 person years, whereas there was more variation in GC incidence in patients with IM (0.38 to 17.08 per 1000 person years). The greatest GC incidence rates were in Asian countries, for patients with GA, and the USA for those with IM (15.24 and 17.08 per 1000 person years, respectively). The largest studies (four over 25,000 person years) had an incidence rate range of 1.0–2.5 per 1000 person years, however, in general, study quality was poor and there was marked heterogeneity.ConclusionOverall there is a wide variation in annual incidence rate of GC from premalignant lesions. With the recent introduction of surveillance guidelines for gastric atrophy and intestinal metaplasia in the Western world, future assessment of this risk should be performed. Furthermore, substantial heterogeneity supports the need for more robust studies in order to pool results and determine the overall incidence rate of gastric cancer for patients with these premalignant lesions.

Low-dose Aspirin Use Does Not Increase Survival in 2 Independent Population-based Cohorts of Patients With Esophageal or Gastric Cancer

BACKGROUND & AIMS Preclinical studies have shown aspirin to have anticancer properties and epidemiologic studies have associated aspirin use with longer survival times of patients with cancer. We studied 2 large cohorts to determine the association between aspirin use and cancer-specific mortality in patients with esophageal or gastric cancer. METHODS We performed a population-based study using cohorts of patients newly diagnosed with esophageal or gastric cancer, identified from cancer registries in England from 1998 through 2012 and the Scottish Cancer Registry from 2009 through 2012. Low-dose aspirin prescriptions were identified from linkages to the United Kingdom Clinical Research Practice Datalink in England and the Prescribing Information System in Scotland. Deaths were identified from linkage to national mortality records, with follow-up until September 2015 in England and January 2015 in Scotland. Time-dependent Cox regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for cancer-specific mortality by low-dose aspirin use after adjusting for potential confounders. Meta-analysis was used to pool results across the 2 cohorts. RESULTS The combined English and Scottish cohorts contained 4654 patients with esophageal cancer and 3833 patients with gastric cancer, including 3240 and 2392 cancer-specific deaths, respectively. The proportions surviving 1 year, based on cancer-specific mortality, were similar in aspirin users vs non-users after diagnosis with esophageal cancer (48% vs 50% in England and 49% vs 46% in Scotland, respectively) or gastric cancer (58% vs 57% in England and 59% vs 55% in Scotland, respectively). There was no association between postdiagnosis use of low-dose aspirin and cancer-specific mortality among patients with esophageal cancer (pooled adjusted HR, 0.98; 95% CI, 0.89-1.09) or gastric cancer (pooled adjusted HR, 0.96; 95% CI, 0.85-1.08). Long-term aspirin use was not associated with cancer-specific mortality after diagnosis of esophageal cancer (pooled adjusted HR, 1.03; 95% CI, 0.85-1.25) or gastric cancer (pooled adjusted HR, 1.06; 95% CI, 0.85-1.32). CONCLUSIONS In analyses of 2 large independent cohorts in the United Kingdom, low-dose aspirin usage was not associated with increased survival of patients diagnosed with esophageal or gastric cancer.

Statin use after esophageal cancer diagnosis and survival: A population based cohort study

BACKGROUND A recent epidemiological study of esophageal cancer patients concluded statin use post-diagnosis was associated with large (38%) and significant reductions in cancer-specific mortality. We investigated statin use and cancer-specific mortality in a large population-based cohort of esophageal cancer patients. METHODS Newly diagnosed [2009-2012] esophageal cancer patients were identified from the Scottish Cancer Registry and linked with the Prescribing Information System and Scotland Death Records (to January 2015). Time-dependent Cox regression models were used to calculate hazard ratios (HR) for cancer-specific mortality and 95% confidence intervals (CIs) by post-diagnostic statin use (using a 6 month lag to reduce reverse causation) and to adjust these HRs for potential confounders. RESULTS 1921 esophageal cancer patients were included in the main analysis, of whom 651 (34%) used statins after diagnosis. There was little evidence of a reduction in esophageal cancer-specific mortality in statin users compared with non-users after diagnosis (adjusted HR=0.93, 95% CI, 0.81, 1.07) and no dose response associations were seen. However, statin users compared with non-users in the year before diagnosis had a weak reduction in esophageal cancer-specific mortality (adjusted HR=0.88, 95% CI, 0.79, 0.99). CONCLUSIONS In this large population-based esophageal cancer cohort, there was little evidence of a reduction in esophageal cancer-specific mortality with statin use after diagnosis.

Physical activity, sedentary behaviour and risk of oesophago-gastric cancer: a prospective cohort study within UK Biobank

Background Few observational studies have assessed the role of physical activity in oesophago-gastric cancer risk. Objective This prospective cohort study aimed to assess the association between physical activity and risk of oesophageal or gastric cancer. Methods A cohort of 359,033 adults aged 40–69 years were identified from the UK Biobank, which recruited participants between 2006 and 2010. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between self-reported levels of physical activity and screen-based sedentary behaviour and risk of oesophageal and gastric cancer were calculated using Cox proportional hazards models. Results During eight years of follow-up (mean = 5.5), 294 oesophageal cancer and 217 gastric cancer cases were identified. Physical activity and screen-based sedentary behaviour levels were not associated with overall oesophago-gastric cancer risk. However, when compared with low levels, high physical activity levels were associated with a significantly reduced risk of gastric non-cardia cancer (HR 0.58, 95% CI 0.37–0.95). Moderate physical activity levels were associated with a 38% reduced risk of oesophageal adenocarcinoma (HR 0.62, 95% CI 0.43–0.89), although no dose-response association was apparent. Conclusion Moderate, rather than high, physical activity levels were associated with the strongest reductions in oesophageal adenocarcinoma risk in this large UK prospective cohort.

Angiotensin receptor blocker use and gastro-oesophageal cancer survival: a population-based cohort study

Angiotensin receptor blockers (ARBs; including candesartan, losartan, olmesartan and valsartan) are widely used to treat hypertension, heart failure and diabetic neuropathy. There is considerable pre‐clinical evidence that ARBs can reduce cancer progression, particularly for gastric cancer. Despite this, epidemiological studies have yet to assess the impact of ARB use on gastro‐oesophageal cancer survival.

Hormonal and reproductive factors and risk of upper gastrointestinal cancers in men: A prospective cohort study within the UK Biobank: Hormonal and reproductive factors and upper gastrointestinal cancers in men

Incidence of upper gastrointestinal cancers of the oesophagus and stomach show a strong unexplained male predominance. Hormonal and reproductive factors have been associated with upper gastrointestinal cancers in women but there is little available data on men. To investigate this, we included 219,425 men enrolled in the UK Biobank in 2006–2010. Baseline assessments provided information on hormonal and reproductive factors (specifically hair baldness, number of children fathered, relative age at first facial hair and relative age voice broke) and incident oesophageal or gastric cancers were identified through linkage to U.K. cancer registries. Unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models. During 8 years of follow‐up, 309 oesophageal 210 gastric cancers occurred. There was some evidence that male pattern baldness, was associated with gastric cancer risk (adjusted HR 1.35, 95% CI 0.97, 1.88), particularly for frontal male pattern baldness (adjusted HR 1.52, 95% CI 1.02, 2.28). There was little evidence of association between other hormonal and reproductive factors and risk of oesophageal or gastric cancer, overall or by histological subtype. In the first study of a range of male hormonal and reproductive factors and gastric cancer, there was a suggestion that male pattern baldness, often used as a proxy of sex hormone levels, may be associated with gastric cancer. Future prospective studies that directly test circulating sex steroid hormone levels in relation to upper gastrointestinal cancer risk are warranted.

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: an analysis of two independent population-based databases

Excessive lower oesophageal sphincter relaxation increases gastro‐oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, β2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case–control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self‐reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from β2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from β2 agonists. This increased cancer risk in β2 agonist users merits further investigation.

Model for Identifying Individuals at Risk for Esophageal Adenocarcinoma

BACKGROUND & AIMS The prognosis for most patients with esophageal adenocarcinoma (EAC) is poor because they present with advanced disease. Models developed to identify patients at risk for EAC and increase early detection have been developed based on data from case–control studies. We analyzed data from a prospective study to identify factors available to clinicians that identify individuals with a high absolute risk of EAC. METHODS We collected data from 355,034 individuals (all older than 50 years) without a prior history of cancer enrolled in the UK Biobank prospective cohort study from 2006 through 2010; clinical data were collected through September 2014. We identified demographic, lifestyle, and medical factors, measured at baseline, that associated with development of EAC within 5 years using logistic regression analysis. We used these data to create a model to identify individuals at risk for EAC. Model performance was assessed using area under the receiver operating characteristics curve (AUROC), sensitivity, and specificity analyses. RESULTS Within up to 5 years of follow up, 220 individuals developed EAC. Age, sex, smoking, body mass index, and history of esophageal conditions or treatments identified individuals who developed EAC (AUROC, 0.80; 95% CI, 0.77–0.82). We used these factors to develop a scoring system and identified a point cut off that 104,723 individuals (29.5%), including 170 of the 220 cases with EAC, were above. The scoring system identified individuals who developed EAC with 77.4% sensitivity and 70.5% specificity. The 5‐year risk of EAC was 0.16% for individuals with scores above the threshold and 0.02% for individuals with scores below the threshold. CONCLUSION We combined data on several well‐established risk factors that are available to clinicians to develop a system to identify individuals with a higher absolute risk of EAC within 5 years. Studies are needed to evaluate the utility of these factors in a multi‐stage, triaged, screening program.

The effect of medications which cause inflammation of the gastro-oesophageal tract on cancer risk : a nested case–control study of routine Scottish data

Bisphosphonate, tetracycline and spironolactone use has been shown to increase gastro‐oesophageal inflammation, an accepted risk factor for cancer. However, evidence of the effect of these medications on gastro‐oesophageal cancer risk are mixed or missing entirely. Therefore, we conducted a nested case–control study using the Primary Care Clinical Information Unit Research (PCCIUR) database from Scotland. Cases with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five controls based on age, gender, year of diagnosis and general practice. Medication use was ascertained using electronic prescribing records. Conditional logistic regression was used to calculate odds ratios (ORs) for the association between medication use and cancer risk after adjustment for comorbidities and other medication use. A similar proportion of gastro‐oesophageal cancer cases received bisphosphonates (3.9% vs. 3.5%), tetracycline (6.0% vs. 6.0%) and spironolactone (1.4% vs. 1.1%) compared with the controls. The adjusted ORs for the association between gastro‐oesophageal cancer and bisphosphonates, tetracycline and spironolactone were 1.05 (95% CI: 0.85, 1.31), 0.99 (95% CI: 0.84, 1.17) and 1.04 (95% CI: 0.73, 1.49). Further analysis revealed bisphosphonates were associated with increased oesophageal cancer risk (1.34, 95% CI: 1.03, 1.74) but reduced gastric cancer risk (0.71, 95% CI: 0.49, 1.03), although there was no obvious dose–response relationship. Overall, there is little evidence that the use of bisphosphonate, tetracycline or spironolactone is associated with increased risk of gastro‐oesophageal cancer. Our findings should reassure GPs and patients that these widely‐used medications are safe with respect to gastro‐oesophageal cancer risk.

59 The association between physical activity and oesophago-gastric cancer: a prospective cohort study within the uk biobank

Background Physical activity has been proposed as a modifiable risk factor for a number of cancers but few observational studies have investigated its effect on oesophageal and gastric carcinoma according to anatomical and histological subsite. Aim This prospective cohort study aims to analyse the association between physical activity and risk of oesophageal or gastric adenocarcinoma. Method A cohort of 3 59 425 adults aged 40-69 years (2006-2010) were identified from the UK biobank who completed a self-report International Physical Activity Questionnaire (IPAQ). Of this cohort, 295 incident oesophageal and 218 gastric cancer cases were identified. Adjusted HRs and 95% CIs for the associations between hours per week from physical activity and categories of physical activity based on IPAQ guidelines (Low, medium and high) and risk of oesophageal cancer and gastric cancer were calculated. Results When compared with low physical activity, high activity was not associated with oesophago-gastric cancer risk. However moderate level physical activity was associated with a reduction in risk of oesophageal adenocarcinoma by 35% after adjustment for confounders (adjusted HR=0.65, 95% CI 0.45 to 0.95). This held for moderate vs low physical activity and any oesophago-gatric adenocarcinoma (adjusted HR=0.70, 95% CI 0.53 to 0.92). This protective effect was not observed for oesophageal squamous cell carcinoma or total gastric cancer risk across physical activity categories. Conclusions In this large prospective cohort, high physical activity levels were not associated with overall risk of oesophago-gastric cancer. However, moderate physical activity was associated with a reduced risk of oesophageal adenocarcinoma tumours.