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      Risk of lung cancer in patients with gastro-esophageal reflux disease: a population-based cohort study

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      1 , 2 , 3 , , 4 ,
      PeerJ
      PeerJ Inc.
      Lung cancer, GERD, Risk factors

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          Abstract

          This large-scale, controlled cohort study estimated the risks of lung cancer in patients with gastro-esophageal reflux disease (GERD) in Taiwan. We conducted this population-based study using data from the National Health Insurance Research Database of Taiwan during the period from 1997 to 2010. Patients with GERD were diagnosed using endoscopy, and controls were matched to patients with GERD at a ratio of 1:4. We identified 15,412 patients with GERD and 60,957 controls. Compared with the controls, the patients with GERD had higher rates of osteoporosis, diabetes mellitus, asthma, chronic obstructive pulmonary disease, pneumonia, bronchiectasis, depression, anxiety, hypertension, dyslipidemia, chronic liver disease, congestive heart failure, atrial fibrillation, stroke, chronic kidney disease, and coronary artery disease (all P < .05). A total of 85 patients had lung cancer among patients with GERD during the follow-up of 42,555 person-years, and the rate of lung cancer was 0.0020 per person-year. By contrast, 232 patients had lung cancer among patients without GERD during the follow-up of 175,319 person-years, and the rate of lung cancer was 0.0013 per person-year. By using stepwise Cox regression model, the overall incidence of lung cancer remained significantly higher in the patients with GERD than in the controls (hazard ratio, 1.53; 95% CI [1.19–1.98]). The cumulative incidence of lung cancer was higher in the patients with GERD than in the controls ( P = .0012). In conclusion, our large population-based cohort study provides evidence that GERD may increase the risk of lung cancer in Asians.

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          Most cited references31

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          Time trends of gastroesophageal reflux disease: a systematic review.

          H Serag (2006)
          There is a perception that the prevalence of gastroesophageal reflux disease (GERD) is increasing, but few studies have directly tackled this issue. By using a systematic approach, this review aimed to assess objectively whether the prevalence of GERD is changing with time. First, population-based studies that reported the prevalence of at least weekly heartburn and/or acid regurgitation were subjected to a time-trend analysis with a Poisson regression model. Second, population-based studies reporting the prevalence of GERD symptoms at 2 time points in the same source population were reviewed. Third, longitudinal studies that charted the prevalence of GERD symptoms and esophagitis in primary and secondary care were examined. The Poisson model revealed a significant (P < .0001) trend for an increase in the prevalence of reflux symptoms in the general population over time. Separately, significant increases with time were found for North America (P = .0005) and Europe (P < .0001) but not Asia (P = .49). Studies of the same source population over time indicated an increase in the prevalence of GERD in the U.S., Singapore, and China but not Sweden. An increase in the prevalence of GERD or esophagitis was found in the majority of longitudinal studies. There is evidence that the prevalence of GERD has increased during the past 2 decades. If this trend continues, it could contribute to the rapidly increasing incidence of more serious complications associated with GERD, such as esophageal adenocarcinoma, as well as costs to healthcare systems and employers.
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            Gastro-oesophageal reflux disease.

            Gastro-oesophageal reflux disease refers to reflux of gastric contents into the oesophagus leading to oesophagitis, reflux symptoms sufficient to impair quality of life, or long-term complications. Transient relaxation of the lower oesophageal sphincter is believed to be the primary mechanism of the disease although the underlying cause remains uncertain. Obesity and smoking are weakly associated with the disease and genetic factors might be important. A negative association with Helicobacter pylori exists, but eradication of H pylori does not seem to cause reflux disease. Diagnosis is imprecise as there is no gold standard. Reflux symptoms are helpful in diagnosis but they lack sensitivity. Ambulatory oesophageal pH monitoring also seems to be insensitive despite high specificity. Empirical acid suppression with a proton-pump inhibitor (PPI) has reasonable sensitivity but poor specificity. Some evidence suggests that once patients develop the disease, severity is determined early and patients seem to continue with that phenotype long term. Unfortunately, most patients do not respond to life-style advice and require further therapy. H2 receptor antagonists and PPIs are better than placebo in oesophagitis, with a number needed to treat of five and two, respectively. In non-erosive reflux disease, acid suppression is better than placebo but the response rate is lower. Most patients need long-term treatment because the disease usually relapses. The role of endoscopic therapy is uncertain. Anti-reflux surgery is probably as effective as PPI therapy although there is a low operative mortality and morbidity.
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              Lung cancer and incidence of stroke: a population-based cohort study.

              Stroke is a known cerebrovascular complication in lung cancer patients; however, whether lung cancer patients are at elevated risk of developing stroke relative to the noncancer population remains unclear. The present study used population-based claims data from the Taiwan National Health Insurance, which identified 52,089 patients with an initial diagnosis of lung cancer between 1999 and 2007, and 104,178 matched noncancer subjects from all insured subjects age 20 years and older. Subsequent occurrence of stroke was measured until 2008, and the association between lung cancer and the hazard of developing stroke was estimated using Cox proportional hazard models. The incidence of stroke was 1.5 times higher (25.9 versus 17.4 per 1000 person-years) in the lung cancer group compared with the comparison group. The multivariate-adjusted hazard ratio (HR) comparing lung cancer patients with the noncancer group was 1.47 (95% CI, 1.39-1.56) for stroke, 1.78 (95% CI, 1.54-2.05) for hemorrhagic stroke, and 1.43 (95% CI, 1.34-1.51) for ischemic stroke. The risk of stroke fell over time, decreasing after 1 year of follow-up for men and after 2 years of follow-up for women. Within the first year of follow-up, the risk of stroke peaked during the first 3 months for men and within 4 to 6 months for women. Lung cancer is associated with increased risk of subsequent stroke within 1 year after diagnosis for men and 2 years after diagnosis for women.
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                Author and article information

                Contributors
                Journal
                PeerJ
                PeerJ
                peerj
                peerj
                PeerJ
                PeerJ Inc. (San Francisco, USA )
                2167-8359
                20 December 2016
                2016
                : 4
                : e2753
                Affiliations
                [1 ]Department of Internal Medicine, E-Da Hospital , Kaohsiung, Taiwan
                [2 ]Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying , Tainan, Taiwan
                [3 ]Department of Internal Medicine, Cardinal Tien Hospital , New Taipei City, Taiwan
                [4 ]National Health Research Institutes , Miaoli, Taiwan
                Article
                2753
                10.7717/peerj.2753
                5178340
                28028458
                b46a2c13-1b53-4864-983a-dc3b333be251
                ©2016 Hsu et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, reproduction and adaptation in any medium and for any purpose provided that it is properly attributed. For attribution, the original author(s), title, publication source (PeerJ) and either DOI or URL of the article must be cited.

                History
                : 30 May 2016
                : 4 November 2016
                Funding
                Funded by: National Health Research Institutes
                This study was supported by grants from National Health Research Institutes (intramural funding). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Epidemiology
                Gastroenterology and Hepatology
                Oncology

                lung cancer,gerd,risk factors
                lung cancer, gerd, risk factors

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