Vitamin D receptor gene variants and esophageal adenocarcinoma risk:A population-based case-control study

Purpose: Polymorphisms in the vitamin D receptor (VDR) gene may be of etiological importance in determining cancer risk. The aim of this study was to assess the association between common VDR gene polymorphisms and esophageal adenocarcinoma (EAC) risk in an all-Ireland population-based case-control study. Methods: EAC cases and frequency-matched controls by age and gender recruited between March 2002 and December 2004 throughout Ireland were included. Participants were interviewed, and a blood sample collected for DNA extraction. Twenty-seven single nucleotide polymorphisms in the VDR gene were genotyped using Sequenom or TaqMan assays while the poly(A) microsatellite was genotyped by fluorescent fragment analysis. Unconditional logistic regression was applied to assess the association between VDR polymorphisms and EAC risk. Results: A total of 224 cases of EAC and 256 controls were involved in analyses. After adjustment for potential confounders, TT homozygotes at rs2238139 and rs2107301 had significantly reduced risks of EAC compared with CC homozygotes. In contrast, SS alleles of the poly(A) microsatellite had significantly elevated risks of EAC compared with SL/LL alleles. However, following permutation analyses to adjust for multiple comparisons, no significant associations were observed between any VDR gene polymorphism and EAC risk. Conclusions: VDR gene polymorphisms were not significantly associated with EAC development in this Irish population. Confirmation is required from larger studies. © Springer Science+Business Media, LLC 2011.

Prescribing for weight loss in primary care: evidence from a population based study

Background Taking antiobesity medication can be a cost effective way to lose weight. Uptake is determined in part by a General Practitioner's decision to prescribe weight loss medication and, in part, by patient preference. It is probable that the latter may indicate a patient's readiness to lose weight.


Methods Analysis of cross-sectional data (from February 2003 to March 2011) from a population based prescribing database (~1.75 million people) using an adjusted Poisson regression.


Results The number of antiobesity medications increased from 23.4 per 1000 population in 2004 to 30.7 per 1000 population in 2010 and was three times higher in female than in male subjects. Against this background, a marked seasonal variation in the number of antiobesity medications dispensed was evident (p<0.001), peaking in June/July with a trough in December/January (±8.0% peak to trough). The seasonal component was stronger in female subjects, ±11.2% peak to trough, compared with ±3.5% for male subjects.


Conclusions Obese patients, particularly women, increase their uptake of weight loss medication in the months leading up to the summer holiday period. The period prior to the summer may represent a time that health professionals could promote increased participation of obese patients in weight loss programmes.

Incidence of colorectal cancer in a population-based cohort of patients with Barrett's oesophagus

Objective. Previous studies have shown a positive association between colorectal cancer and Barrett's oesophagus, but this association is disputed. No population-based studies have examined the incidence of this cancer in patients with Barrett's oesophagus. Material and methods. The present study comprised a population-based cohort of patients with Barrett's oesophagus (constructed using pathology reports of all oesophageal biopsies in Northern Ireland 1993-99; cohort subclassified according to whether specialized intestinal metaplasia (SIM) was present, absent, or not commented on in biopsies). Cases of colorectal cancer were identified by linking with the Northern Ireland Cancer Registry. The comparison group used was the general population in Northern Ireland. Results. A total of 2969 patients with Barrett's oesophagus were followed for a total of 14,014 person-years (mean 4.7 years). SIM was present in 1670 patients (56.2%), absent in 545 (18.4%) and not commented on in 754 (25.4%). Colorectal cancer was diagnosed in 39 patients; 22 patients had cancer diagnosed at least 6 months after diagnosis of Barrett's oesophagus. There was no increased risk of colorectal cancer: the standardized incidence ratio (SIR) for cancer diagnosed at least 6 months after entry into the cohort was 0.82 (95% CI, 0.48-1.17); this risk did not alter with SIM status or gender. To assess a possible effect of diagnostic bias, we calculated SIRs for cancers occurring after at least 3 months, after at least 1 month and at any time after diagnosis of Barrett's oesophagus. These were 0.94 (0.57-1.30), 1.09 (0.69-1.48) and 1.46 (1.00-1.92), respectively. Conclusions. The incidence of colorectal cancer was not elevated in patients with Barrett's oesophagus. Diagnostic bias may explain why previous studies have found an association. © 2005 Taylor & Francis.

Risk of Several Cancers is Higher in Urban Areas after Adjusting for Socioeconomic Status. Results from a Two-Country Population-Based Study of 18 Common Cancers

Some studies suggest that there are urban-rural variations in cancer incidence but whether these simply reflect urban-rural socioeconomic variation is unclear. We investigated whether there were urban-rural variations in the incidence of 18 cancers, after adjusting for socioeconomic status. Cancers diagnosed between 1995 and 2007 were extracted from the population-based National Cancer Registry Ireland and Northern Ireland Cancer Registry and categorised by urban-rural status, based on population density of area of residence at diagnosis (rural 15 people per hectare). Relative risks (RR) were calculated by negative binomial regression, adjusting for age, country and three area-based markers of socioeconomic status. Risks were significantly higher in both sexes in urban than rural residents with head and neck (males RR urban vs. rural = 1.53, 95 % CI 1.42-1.64; females RR = 1.29, 95 % CI 1.15-1.45), esophageal (males 1.21, 1.11-1.31; females 1.21, 1.08-1.35), stomach (males 1.36, 1.27-1.46; females 1.19, 1.08-1.30), colorectal (males 1.14, 1.09-1.18; females 1.04, 1.00-1.09), lung (males 1.54, 1.47-1.61; females 1.74, 1.65-1.84), non-melanoma skin (males 1.13, 1.10-1.17; females 1.23, 1.19-1.27) and bladder (males 1.30, 1.21-1.39; females 1.31, 1.17-1.46) cancers. Risks of breast, cervical, kidney and brain cancer were significantly higher in females in urban areas. Prostate cancer risk was higher in rural areas (0.94, 0.90-0.97). Other cancers showed no significant urban-rural differences. After adjusting for socioeconomic variation, urban-rural differences were evident for 12 of 18 cancers. Variations in healthcare utilization and known risk factors likely explain some of the observed associations. Explanations for others are unclear and, in the interests of equity, warrant further investigation. © 2014 The New York Academy of Medicine.

Hazardous alcohol consumption is associated with increased levels of B-type natriuretic peptide: evidence from two population-based studies

Russia has very high mortality from cardiovascular disease (CVD), with evidence that heavy drinking may play a role. To throw further light on this association we have studied the association of alcohol with predictors of CVD risk including B-type natriuretic peptide (BNP). Levels of BNP increase primarily in response to abnormal cardiac chamber wall stretch which can occur both as a result of atherosclerosis as well as due to other types of damage to the myocardium. No previous population-based studies have investigated the association with alcohol. We analysed cross-sectional data on drinking behaviour in 993 men aged 25-60 years from the Izhevsk Family Study 2 (IFS2), conducted in the Russian city of Izhevsk in 2008-2009. Relative to non-drinkers, men who drank hazardously had an odds ratio (OR) of being in the top 20 % of the BNP distribution of 4.66 (95 % CI 2.13, 10.19) adjusted for age, obesity, waist-hip ratio, and smoking. Further adjustment for class of hypertension resulted in only slight attenuation of the effect, suggesting that this effect was not secondary to the influence of alcohol on blood pressure. In contrast hazardous drinking was associated with markedly raised ApoA1 and HDL cholesterol levels, but had little impact on levels of ApoB and LDL cholesterol. Similar but less pronounced associations were found in the Belfast (UK) component of the PRIME study conducted in 1991. These findings suggest that the association of heavy drinking with increased risk of cardiovascular disease may be partly due to alcohol-induced non-atherosclerotic damage to the myocardium.

Drugs affecting the renin-angiotensin system and survival from cancer: a population based study of breast, colorectal and prostate cancer patient cohorts

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are commonly prescribed to the growing number of cancer patients (more than two million in the UK alone) often to treat hypertension. However, increased fatal cancer in ARB users in a randomized trial and increased breast cancer recurrence rates in ACEI users in a recent observational study have raised concerns about their safety in cancer patients. We investigated whether ACEI or ARB use after breast, colorectal or prostate cancer diagnosis was associated with increased risk of cancer-specific mortality.

Methods: Population-based cohorts of 9,814 breast, 4,762 colorectal and 6,339 prostate cancer patients newly diagnosed from 1998 to 2006 were identified in the UK Clinical Practice Research Datalink and confirmed by cancer registry linkage. Cancer-specific and all-cause mortality were identified from Office of National Statistics mortality data in 2011 (allowing up to 13 years of follow-up). A nested case–control analysis was conducted to compare ACEI/ARB use (from general practitioner prescription records) in cancer patients dying from cancer with up to five controls (not dying from cancer). Conditional logistic regression estimated the risk of cancer-specific, and all-cause, death in ACEI/ARB users compared with non-users.

Results: The main analysis included 1,435 breast, 1,511 colorectal and 1,184 prostate cancer-specific deaths (and 7,106 breast, 7,291 colorectal and 5,849 prostate cancer controls). There was no increase in cancer-specific mortality in patients using ARBs after diagnosis of breast (adjusted odds ratio (OR) = 1.06 95% confidence interval (CI) 0.84, 1.35), colorectal (adjusted OR = 0.82 95% CI 0.64, 1.07) or prostate cancer (adjusted OR = 0.79 95% CI 0.61, 1.03). There was also no evidence of increases in cancer-specific mortality with ACEI use for breast (adjusted OR = 1.06 95% CI 0.89, 1.27), colorectal (adjusted OR = 0.78 95% CI 0.66, 0.92) or prostate cancer (adjusted OR = 0.78 95% CI 0.66, 0.92).

Conclusions: Overall, we found no evidence of increased risks of cancer-specific mortality in breast, colorectal or prostate cancer patients who used ACEI or ARBs after diagnosis. These results provide some reassurance that these medications are safe in patients diagnosed with these cancers.

Keywords: Colorectal cancer; Breast cancer; Prostate cancer; Mortality; Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers

Oesophageal adenocarcinoma and prior diagnosis of Barrett's oesophagus: a population-based study

Objective: Endoscopic surveillance of Barrett's oesophagus (BO) provides an opportunity to detect early stage oesophageal adenocarcinoma (OAC). We sought to determine the proportion of OAC patients with a prior diagnosis of BO on a population basis and to evaluate the influence of a prior diagnosis of BO on survival, taking into account lead and length time biases.

Design: A retrospective population-based study of all OAC patients in Northern Ireland between 2003 and 2008. A prior BO diagnosis was determined by linkage to the Northern Ireland BO register. Stage distribution at diagnosis and histological grade were compared between patients with and without a prior BO diagnosis. Overall survival, using Cox models, was compared between patients with and without a prior BO diagnosis. The effect of adjusting the survival differences for histological grade and estimates of lead and length time bias was assessed.

Results: There were 716 OAC cases, 52 (7.3%) of whom had a prior BO diagnosis. Patients with a prior BO diagnosis had significantly lower tumour stage (44.2% vs 11.1% had stage 1 or 2 disease; p<0.001), a higher rate of surgical resection (50.0% vs 25.5%; p<0.001) and had a higher proportion of low/intermediate grade tumours (46.2% vs 26.5%; p=0.011). A prior BO diagnosis was associated with significantly better survival (HR for death 0.39; 95% CI 0.27 to 0.58), which was minimally influenced by adjustment for age, sex and tumour grade (adjusted HR 0.44; 95% CI 0.30 to 0.64). Correction for lead time bias attenuated but did not abolish the survival benefit (HR 0.65; 95% CI 0.45 to 0.95) and further adjustment for length time bias had little effect.

Conclusions: The proportion of OAC patients with a prior diagnosis of BO is low; however, prior identification of BO is associated with an improvement in survival in OAC patients.

Beta-blocker usage after malignant melanoma diagnosis and survival: a population-based nested case-control study

Background: Beta-blockers have potential antiangiogenic and antimigratory activity. Studies have demonstrated a survival benefit in patients with malignant melanoma treated with beta-blockers.

Objectives: To investigate the association between postdiagnostic beta-blocker usage and risk of melanoma-specific mortality in a population-based cohort of patients with malignant melanoma.

Methods: Patients with incident malignant melanoma diagnosed between 1998 and 2010 were identified within the U.K. Clinical Practice Research Datalink and confirmed using cancer registry data. Patients with malignant melanoma with a melanoma-specific death (cases) recorded by the Office of National Statistics were matched on year of diagnosis, age and sex to four malignant melanoma controls (who lived at least as long after diagnosis as their matched case). A nested case–control approach was used to investigate the association between postdiagnostic beta-blocker usage and melanoma-specific death and all-cause mortality. Conditional logistic regression was applied to generate odds ratios (ORs) and 95% confidence intervals (CIs) for beta-blocker use determined from general practitioner prescribing.

Results: Beta-blocker medications were prescribed after malignant melanoma diagnosis to 20·2% of 242 patients who died from malignant melanoma (cases) and 20·3% of 886 matched controls. Consequently, there was no association between beta-blocker use postdiagnosis and cancer-specific death (OR 0·99, 95% CI 0·68–1·42), which did not markedly alter after adjustment for confounders including stage (OR 0·87, 95% CI 0·56–1·34). No significant associations were detected for individual beta-blocker types, by defined daily doses of use or for all-cause mortality.

Conclusions: Contrary to some previous studies, beta-blocker use after malignant melanoma diagnosis was not associated with reduced risk of death from melanoma in this U.K. population-based study.

Survival for haematological malignancies in Europe between 1997 and 2008 by region and age: results of EUROCARE-5, a population-based study

Background: More effective treatments have become available for haematological malignancies from the early 2000s, but few large-scale population-based studies have investigated their effect on survival. Using EUROCARE data, and HAEMACARE morphological groupings, we aimed to estimate time trends in population-based survival for 11 lymphoid and myeloid malignancies in 20 European countries, by region and age. Methods: In this retrospective observational study, we included patients (aged 15 years and older) diagnosed with haematological malignancies, diagnosed up to Dec 31, 2007, and followed up to Dec 31, 2008. We used data from the 30 cancer registries (across 20 countries) that provided continuous incidence and good quality data from 1992 to 2007. We used a hybrid approach to estimate age-standardised and age-specific 5-year relative survival, for each malignancy, overall and for five regions (UK, and northern, central, southern, and eastern Europe), and four 3-year periods (1997–99, 2000–02, 2003–05, 2006–08). For each malignancy, we also estimated the relative excess risk of death during the 5 years after diagnosis, by period, age, and region. Findings: We analysed 560 444 cases. From 1997–99 to 2006–08 survival increased for most malignancies: the largest increases were for diffuse large B-cell lymphoma (42·0% [95% CI 40·7–43·4] to 55·4% [54·6–56·2], p<0·0001), follicular lymphoma (58·9% [57·3–60·6] to 74·3% [72·9–75·5], p<0·0001), chronic myeloid leukaemia (32·3% [30·6–33·9] to 54·4% [52·5–56·2], p<0·0001), and acute promyelocytic leukaemia (50·1% [43·7–56·2] to 61·9% [57·0–66·4], p=0·0038, estimate not age-standardised). Other survival increases were seen for Hodgkin's lymphoma (75·1% [74·1–76·0] to 79·3% [78·4–80·1], p<0·0001), chronic lymphocytic leukaemia/small lymphocytic lymphoma (66·1% [65·1–67·1] to 69·0% [68·1–69·8], p<0·0001), multiple myeloma/plasmacytoma (29·8% [29·0–30·6] to 39·6% [38·8–40·3], p<0·0001), precursor lymphoblastic leukaemia/lymphoma (29·8% [27·7–32·0] to 41·1% [39·0–43·1], p<0·0001), acute myeloid leukaemia (excluding acute promyelocytic leukaemia, 12·6% [11·9–13·3] to 14·8% [14·2–15·4], p<0·0001), and other myeloproliferative neoplasms (excluding chronic myeloid leukaemia, 70·3% [68·7–71·8] to 74·9% [73·8–75·9], p<0·0001). Survival increased slightly in southern Europe, more in the UK, and conspicuously in northern, central, and eastern Europe. However, eastern European survival was lower than that for other regions. Survival decreased with advancing age, and increased with time only slightly in patients aged 75 years or older, although a 10% increase in survival occurred in elderly patients with follicular lymphoma, diffuse large B-cell lymphoma, and chronic myeloid leukaemia. Interpretation: These trends are encouraging. Widespread use of new and more effective treatment probably explains much of the increased survival. However, the persistent differences in survival across Europe suggest variations in the quality of care and availability of the new treatments. High-resolution studies that collect data about stage at diagnosis and treatments for representative samples of cases could provide further evidence of treatment effectiveness and explain geographic variations in survival.

Common community-acquired infections and subsequent risk of multiple myeloma: a population-based study

The role of bacteria and viruses as aetiological agents in the pathogenesis of cancer has been well established for several sites, including a number of haematological malignancies. Less clear is the impact of such exposures on the subsequent development of multiple myeloma (MM). Using the population-based U.S. Surveillance Epidemiology and End Results-Medicare dataset, 15,318 elderly MM and 200,000 controls were identified to investigate the impact of 14 common community-acquired infections and risk of MM. Odds ratios (ORs) and associated 95% confidence intervals (CIs) were adjusted for sex, age and calendar year of selection. The 13-month period prior to diagnosis/selection was excluded. Risk of MM was increased by 5-39% following Medicare claims for eight of the investigated infections. Positive associations were observed for several infections including bronchitis (adjusted OR 1.14, 95% CI 1.09-1.18), sinusitis (OR 1.15, 95% CI 1.10-1.20) pneumonia (OR 1.27, 95% CI 1.21-1.33), herpes zoster (OR 1.39, 95% CI 1.29-1.49) and cystitis (OR 1.09, 95% CI 1.05-1.14). Each of these infections remained significantly elevated following the exclusion of more than 6 years of claims data. Exposure to infectious antigens may therefore play a role in the development of MM. Alternatively, the observed associations may be a manifestation of an underlying immune disturbance present several years prior to MM diagnosis and thereby part of the natural history of disease progression.

Feasibility trial of a film-based educational intervention for increasing boy's and girl's intentions to avoid teenage pregnancy: study protocol

The World Health Organisation, amongst others, recognises that adolescent men have a vital yet neglected role in reducing teenage pregnancies and that there is a pressing need for educational interventions designed especially for them. This study seeks to fill this gap by determining the feasibility of conducting an effectiveness trial of the If I Were Jack intervention in post-primary schools. This 4-week intervention aims to increase teenagers' intentions to avoid unintended pregnancy and addresses gender inequalities in sex education by explicitly focusing on young men. A cluster randomised feasibility trial with embedded process evaluation will determine: recruitment, participation and retention rates; quality of implementation; acceptability and feasibility of the intervention and trial procedures; and costs. (C) 2014 The Authors. Published by Elsevier Ltd.

Are family physician visits and continuity of care associated with acute care use at end-of-life? A population-based cohort study of homecare cancer patients

Background: Previous end-of-life cancer research has shown an association between increased family physician continuity of care and reduced use of acute care services; however, it did not focus on a homecare population or control for homecare nursing.

Aim: Among end-of-life homecare cancer patients, to investigate the association of family physician continuity with location of death and hospital and emergency department visits in the last 2 weeks of life while controlling for nursing hours.

Design: Retrospective population-based cohort study.

Setting/participants: Cancer patients with ≥1 family physician visit in 2006 from Ontario, Canada. Family physician continuity of care was assessed using two measures: Modified Usual Provider of Care score and visits/week. Its association with location of death and hospital and emergency department visits in the last 2 weeks of life was examined using logistic regression.

Results: Of 9467 patients identified, the Modified Usual Provider of Care score demonstrated a dose-response relationship with increasing continuity associated with decreased odds of hospital death and visiting the hospital and emergency department in the last 2 weeks of life. More family physician visits/week were associated with lower odds of an emergency department visit in the last 2 weeks of life and hospital death, except for patients with greater than 4 visits/week, where they had increased odds of hospitalizations and hospital deaths.

Conclusions: These results demonstrate an association between increased family physician continuity of care and decreased odds of several acute care outcomes in late life, controlling for homecare nursing and other covariates.©The Author(s) 2013 Reprints and permissions sagepub.co.uk/journalsPermissions.nav.