Cigarette Smoking Increases Risk of Barrett’s Esophagus:An Analysis of the Barrett’s and Esophageal Adenocarcinoma Consortium

Background & Aims: Cigarette smoking has been implicated in the etiology of esophageal adenocarcinoma, but it is not clear if smoking is a risk factor for Barrett's esophagus. We investigated whether tobacco smoking and other factors increase risk for Barrett's esophagus.

Methods: We analyzed data from 5 case-control studies included in the international Barrett's and Esophageal Adenocarcinoma Consortium. We compared data from subjects with Barrett's esophagus (n = 1059) with those from subjects with gastroesophageal reflux disease (gastroesophageal reflux disease controls, n = 1332), and population-based controls (n = 1143), using multivariable logistic regression models to test associations with cigarette smoking. We also tested whether cigarette smoking has synergistic effects with other exposures, which might further increase risk for Barrett's esophagus.

Results: Subjects with Barrett's esophagus were significantly more likely to have ever smoked cigarettes than the population-based controls (odds ratio [OR] = 1.67; 95% confidence interval [CI]: 1.042.67) or gastroesophageal reflux disease controls (OR = 1.61; 95% CI: 1.331.96). Increasing pack-years of smoking increased the risk for Barrett's esophagus. There was evidence of a synergy between ever-smoking and heartburn or regurgitation; the attributable proportion of disease among individuals who ever smoked and had heartburn or regurgitation was estimated to be 0.39 (95% CI: 0.250.52).

Conclusions: Cigarette smoking is a risk factor for Barrett's esophagus. The association was strengthened with increased exposure to smoking until ~20 pack-years, when it began to plateau. Smoking has synergistic effects with heartburn or regurgitation, indicating that there are various pathways by which tobacco smoking might contribute to development of Barrett's esophagus.

Early diagnosis improves survival in kidney cancer

Kidney cancers account for 2-3% of all adult malignancies in the UK. Men are predominantly affected by renal cancer with an average age at diagnosis of 64 years. Renal (or clear) cell carcinoma (RCC) accounts for 90% of kidney cancers. Early diagnosis improves survival with five-year survival rates for renal cancer of 70-94% for localised tumours in the UK. RCC should be suspected in the presence of localising symptoms such as flank pain, a loin mass or haematuria; constitutional upset including weight loss, pyrexia and/or night sweats; or with unexplained laboratory tests. Smoking, obesity and hypertension are the most important and most common risk factors. Environmental exposure to asbestos, cadmium and trichloroethylene are less common risk factors. Patients on chronic dialysis and renal transplant recipients are at increased risk of RCC in their native kidneys. If kidney cancer is suspected on history, physical examination or initial screening tests then a red flag ultrasound examination of the renal tracts should be requested. Dipstick urinalysis is of great value as asymptomatic haematuria may be the only abnormal test in the presence of non-specific symptoms such as weight loss or loin pain. Visible or non-visible haematuria, in the absence of proteinuria, suggests an underlying structural abnormality is present in the kidneys, ureters or bladder. Surgical removal of RCCs, where feasible, may result in cure in up to 40-60% of cases. Individuals too frail for major surgery may benefit from thermal ablation and cryotherapy. Agents that target the VEGF and mTOR pathways are considered first line in the treatment of metastatic RCC. Sunitinib, recommended by NICE, is administered orally and acts by inhibiting the VEGF receptor.

Dietary fat and meat intakes and risk of reflux esophagitis, Barrett's esophagus and esophageal adenocarcinoma

The aim of our study was to investigate whether dietary fat and meat intakes are associated with reflux esophagitis (RE), Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). In this all-Ireland case-control study, dietary intake data were collected using a food frequency questionnaire in 219 RE patients, 220 BE patients, 224 EAC patients and 256 frequency-matched controls between 2002 and 2005. Unconditional multiple logistic regression analysis was used to examine the association between dietary variables and disease risk using quartiles of intake, to attain odds ratios (ORs) and 95% confidence intervals (95% CIs), while adjusting for potential confounders. Patients in the highest quartile of total fat intake had a higher risk of RE (OR = 3.54; 95% CI = 1.32-9.46) and EAC (OR = 5.44; 95% CI = 2.08-14.27). A higher risk of RE and EAC was also reported for patients in the highest quartile of saturated fat intake (OR = 2.79; 95% CI = 1.11-7.04; OR = 2.41; 95% CI = 1.14-5.08, respectively) and monounsaturated fat intake (OR = 2.63; 95% CI = 1.01-6.86; OR = 5.35; 95% CI = 2.14-13.34, respectively). Patients in the highest quartile of fresh red meat intake had a higher risk of EAC (OR = 3.15; 95% CI = 1.38-7.20). Patients in the highest category of processed meat intake had a higher risk of RE (OR = 4.67; 95% CI = 1.71-12.74). No consistent associations were seen for BE with either fat or meat intakes. Further studies investigating the association between dietary fat and food sources of fat are needed to confirm these results.

What do men understand about lifetime risk following genetic testing?:The effect of context and numeracy.

Genetic testing for gene mutations associated with specific cancers provides an opportunity for early detection, surveillance, and intervention (Smith, Cokkinides, & Brawley, 2008). Lifetime risk estimates provided by genetic testing refer to the risk of developing a specific disease within one's lifetime, and evidence suggests that this is important for the medical choices people make, as well as their future family and financial plans. The present studies tested whether adult men understand the lifetime risks of prostate cancer informed by genetic testing. In 2 experiments, adult men were asked to interpret the lifetime risk information provided in statements about risks of prostate cancer. Statement format was manipulated such that the most appropriate interpretation of risk statements referred to an absolute risk of cancer in experiment 1 and a relative risk in experiment 2. Experiment 1 revealed that few men correctly interpreted the lifetime risks of cancer when these refer to an absolute risk of cancer, and numeracy levels positively predicted correct responding. The proportion of correct responses was greatly improved in experiment 2 when the most appropriate interpretation of risk statements referred instead to a relative rather than an absolute risk, and numeracy levels were less involved. Understanding of lifetime risk information is often poor because individuals incorrectly believe that these refer to relative rather than absolute risks of cancer.

Do perinatal and early life exposures influence the risk of malignant melanoma?:A Northern Ireland birth cohort analysis

Aim: Intrauterine, early life and maternal exposures may have important consequences for cancer development in later life. The aim of this study was to examine perinatal and birth characteristics with respect to Cutaneous malignant melanoma (CMM) risk. Methods: The Northern Ireland Child Health System database was used to examine gestational age adjusted birth weight, infant feeding practices, parental age and socioeconomic factors at birth in relation to CMM risk amongst 447,663 infants delivered between January 1971 and December 1986. Follow-up of histologically verified CMM cases was undertaken from the beginning of 1993 to 31st December 2007. Multivariable adjusted unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of CMM risk. Results: A total of 276 CMM cases and 440,336 controls contributed to the final analysis. In reference to normal (gestational age-adjusted) weight babies, those heaviest at birth were twice as likely to develop CMM OR 2.4 (95% CI 1.1-5.1). Inverse associations with CMM risk were observed with younger (

Risk factors, DNA damage, and disease progression in Barrett's esophagus

Esophageal adenocarcinoma develops on a background of Barrett's esophagus. A number of risk factors have been linked to both conditions, including gastroesophageal reflux and smoking. However, the molecular mechanisms by which these factors influence disease progression remain unclear. One possibility is that risk factors generate promutagenic DNA damage in the esophagus. The comet assay was used to measure DNA damage in esophageal (Barrett's and squamous) and gastric mucosa of Barrett's patients with (n = 24) or without (n = 50) associated adenocarcinoma or high-grade dysplasia in comparison with control patients (squamous mucosa) without Barrett's esophagus (n = 64). Patients completed a questionnaire detailing exposure to some of the known risk factors for Barrett's esophagus and adenocarcinoma. In Barrett's esophagus patients, DNA damage was higher in Barrett's mucosa compared with normal esophageal and gastric mucosa (P < 0.001). In addition, the highest quartile of DNA damage in Barrett's mucosa was associated with an increased risk (odds ratio, 9.4; 95% confidence interval, 1.1-83.4; P = 0.044) of developing adenocarcinoma or high-grade dysplasia compared with DNA damage levels in the lowest quartile. Smoking was associated with higher DNA damage in squamous epithelium in all patient groups (P < 0.01) and in Barrett's mucosa (P < 0.05) in Barrett's esophagus patients only. In controls only, current reflux was associated with higher DNA damage, whereas anti-inflammatory drug use resulted in lower levels. Collectively, these data imply a genotoxic insult to the premalignaint Barrett's mucosa that may explain the genetic instability in this tissue and the progression to adenocarcinoma. There is an indication for a role for smoking in inducing DNA damage in esophageal mucosa but an understanding of the role of reflux requires further investigation.

Investigating local relationships between trace elements in soils and cancer data

Medical geology research has recognised a number of potentially toxic elements (PTEs), such as arsenic, cobalt, chromium, copper, nickel, lead, vanadium, uranium and zinc, known to influence human disease by their respective deficiency or toxicity. As the impact of infectious diseases has decreased and the population ages, so cancer has become the most common cause of death in developed countries including Northern Ireland. This research explores the relationship between environmental exposure to potentially toxic elements in soil and cancer disease data across Northern Ireland. The incidence of twelve different cancer types (lung, stomach, leukaemia, oesophagus, colorectal, bladder, kidney, breast, mesothelioma, melanoma and non melanoma(NM) both basal and squamous, were examined in the form of twenty-five coded datasets comprising aggregates over the 12 year period from 1993 to 2006. A local modelling technique,geographically weighted regression (GWR) is usedto explore the relationship between environmental exposure and cancer disease data. The results show comparisons of the geographical incidence of certain cancers (stomach and NM squamous skin cancer) in relation to concentrations of certain PTEs (arsenic levels in soils and radon were identified). Findings from the research have implications for regional human health risk assessments.

RanGTPase: A Candidate for Myc-Mediated Cancer Progression

BackgroundRas-related nuclear protein (Ran) is required for cancer cell survival in vitro and human cancer progression, but the molecular mechanisms are largely unknown.MethodsWe investigated the effect of the v-myc myelocytomatosis viral oncogene homolog (Myc) on Ran expression by Western blot, chromatin immunoprecipitation, and luciferase reporter assays and the effects of Myc and Ran expression in cancer cells by soft-agar, cell adhesion, and invasion assays. The correlation between Myc and Ran and the association with patient survival were investigated in 14 independent patient cohorts (n = 2430) and analyzed with Spearman's rank correlation and Kaplan-Meier plots coupled with Wilcoxon-Gehan tests, respectively. All statistical tests were two-sided.ResultsMyc binds to the upstream sequence of Ran and transactivates Ran promoter activity. Overexpression of Myc upregulates Ran expression, whereas knockdown of Myc downregulates Ran expression. Myc or Ran overexpression in breast cancer cells is associated with cancer progression and metastasis. Knockdown of Ran reverses the effect induced by Myc overexpression in breast cancer cells. In clinical data, a positive association between Myc and Ran expression was revealed in 288 breast cancer and 102 lung cancer specimens. Moreover, Ran expression levels differentiate better or poorer survival in Myc overexpressing breast (?(2) = 24.1; relative risk [RR] = 9.1, 95% confidence interval [CI] = 3.3 to 24.7, P <.001) and lung (?(2) = 6.04; RR = 2.8, 95% CI = 1.2 to 6.3; P = .01) cancer cohorts.ConclusionsOur results suggest that Ran is required for and is a potential therapeutic target of Myc-driven cancer progression in both breast and lung cancers.

A comparative analysis of the health and wellbeing of cancer survivors to the general population

Background
The population of people surviving cancer is continually increasing and currently cancer survivors represent approximately 3.7% of the American population and 3% of the UK population. There is limited and inconclusive empirical evidence regarding the long-term health and well-being of cancer survivors.

Methods
Two hundred eighty-nine cancer survivors and 262 matched-age and sex patients from the same group of General (primary care) Practices completed postal questionnaires measuring health and well-being, health service utilisation and satisfaction and health care needs.

Main Results
Cancer survivors reported poorer health and well-being and health service utilisation than the general population. Despite this poorer health, the majority of cancer survivors reported satisfaction with services and almost two-thirds of the survivors did not report any needs.

Conclusions
The majority of cancer survivors do not appear to require additional support services. There is, however, a subgroup of survivors who warrant specialist support, particularly survivors who are older, experience late effects and have had adjuvant treatments. Future research should focus on developing methods that could be used in routine clinical practice to identify ‘at risk’ or vulnerable patients and to provide appropriate and timely support.

Meta-analysis of three genome-wide association studies identifies susceptibility loci for colorectal cancer at 1q41, 3q26.2, 12q13.13 and 20q13.33.

Genome-wide association studies (GWAS) have identified ten loci harboring common variants that influence risk of developing colorectal cancer (CRC). To enhance the power to identify additional CRC risk loci, we conducted a meta-analysis of three GWAS from the UK which included a total of 3,334 affected individuals (cases) and 4,628 controls followed by multiple validation analyses including a total of 18,095 cases and 20,197 controls. We identified associations at four new CRC risk loci: 1q41 (rs6691170, odds ratio (OR) = 1.06, P = 9.55 × 10?¹° and rs6687758, OR = 1.09, P = 2.27 × 10??, 3q26.2 (rs10936599, OR = 0.93, P = 3.39 × 10?8), 12q13.13 (rs11169552, OR = 0.92, P = 1.89 × 10?¹° and rs7136702, OR = 1.06, P = 4.02 × 10?8) and 20q13.33 (rs4925386, OR = 0.93, P = 1.89 × 10?¹°). In addition to identifying new CRC risk loci, this analysis provides evidence that additional CRC-associated variants of similar effect size remain to be discovered.

Renal cell cancer:Nurses' role in prevention and management

In both the UK and throughout Europe, more patients are presenting with renal cell cancer (RCC), also known as renal cell carcinoma or kidney cancer. The overall survival rate varies depending on tumour grade, nodal involvement and metastasis. For those with metastasis survival drops to 10%. This article explores the risk factors associated with RCC diagnosis and staging, treatments including drugs and procedures and the role of the nurse in diagnosis and accurate assessment. Nurses are ideally suited to consider the physical, functional, social, and emotional status of their patients In addition, it is essential that the nurse has an understanding of new pharmaceutical therapies, which have been licensed to treat RCC, and a sound knowledge of the possible side effects and nursing management associated with these drugs.

PTGS2 (Cyclooxygenase-2) expression and survival among colorectal cancer patients: A systematic review

Background: Studies have examined whether tumor expression of PTGS2 (also known as COX-2), an enzyme inhibited by nonsteroidal anti-inflammatory drugs such as aspirin, is associated with prognosis in patients with colorectal cancer. However, results to date have been mixed. Methods: Using terms for PTGS2 and colorectal cancer, the Medline, Embase, and Web of Science databases were systematically searched for studies published, in any language, until December 2011. Random effects meta-analyses were used to calculate pooled HRs [95% confidence intervals (CI)] for the association between PTGS2 expression and tumor recurrence, colorectal cancer-specific survival, and overall survival. Results: In total, 29 studies, which had prognostic data on 5,648 patients, met the inclusion criteria. PTGS2- positive patients were at an increased risk of tumor recurrence (n = 9 studies; HR, 2.79; 95% CI, 1.76-4.41; P <0.001) and had poorer colorectal cancer-specific survival (n = 7; HR, 1.36; 95% CI, 1.02-1.82; P = 0.04). However, there was funnel plot asymmetry, possibly due to publication bias, for the association with cancerspecific survival but less so for recurrence. PTGS2 expression was not associated with overall survival [(n= 16; pooled unadjusted HR, 1.30; 95% CI, 0.94-1.79; P=0.11) and (n=9; pooled adjusted HR, 1.02; 95% CI, 0.72-1.45; P = 0.91)]. Conclusions: PTGS2 expression was associated with an increased risk of tumor recurrence and poorer colorectal cancer-specific survival but not overall survival among patients with colorectal cancer. However, confounding by tumor characteristics such as tumor stage seems likely. Impact: There is insufficient evidence to recommend PTGS2 expression as a prognostic marker in patients with colorectal cancer. Furthermore, studies providing adjusted results are required. © 2013 AACR.

Differences in cancer awareness and beliefs between Australia, Canada, Denmark, Norway, Sweden and the UK (the International Cancer Benchmarking Partnership):Do they contribute to differences in cancer survival?

Background:There are wide international differences in 1-year cancer survival. The UK and Denmark perform poorly compared with other high-income countries with similar health care systems: Australia, Canada and Sweden have good cancer survival rates, Norway intermediate survival rates. The objective of this study was to examine the pattern of differences in cancer awareness and beliefs across these countries to identify where these might contribute to the pattern of survival.Methods:We carried out a population-based telephone interview survey of 19 079 men and women aged =50 years in Australia, Canada, Denmark, Norway, Sweden and the UK using the Awareness and Beliefs about Cancer measure.Results:Awareness that the risk of cancer increased with age was lower in the UK (14%), Canada (13%) and Australia (16%) but was higher in Denmark (25%), Norway (29%) and Sweden (38%). Symptom awareness was no lower in the UK and Denmark than other countries. Perceived barriers to symptomatic presentation were highest in the UK, in particular being worried about wasting the doctor's time (UK 34%; Canada 21%; Australia 14%; Denmark 12%; Norway 11%; Sweden 9%).Conclusion:The UK had low awareness of age-related risk and the highest perceived barriers to symptomatic presentation, but symptom awareness in the UK did not differ from other countries. Denmark had higher awareness of age-related risk and few perceived barriers to symptomatic presentation. This suggests that other factors must be involved in explaining Denmark's poor survival rates. In the UK, interventions that address barriers to prompt presentation in primary care should be developed and evaluated. © 2013 Cancer Research UK. All rights reserved.

Prospective investigation of body mass index, colorectal adenoma, and colorectal cancer in the prostate, lung, colorectal, and ovarian cancer screening trial

Obesity has consistently been linked to an increased risk of colorectal cancer, particularly among men. Whether body mass index (BMI) differentially influences the risk across the stages of colorectal cancer development remains unclear. We evaluated the associations of BMI with colorectal adenoma incidence, adenoma recurrence, and cancer in the context of a large screening trial, in which cases and controls had an equal chance for disease detection.