Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett's Esophagus, and Gastroesophageal Reflux

Ek, Weronica E.; Levine, David; D’Amato, Mauro; Pedersen, Nancy L.; Magnusson, Patrik K. E.; Bresso, Francesca; Onstad, Lynn; Schmidt, Peter T.; Törnblom, Hans; Nordenstedt, Helena; Romero, Yvonne; Chow, Wong Ho; Murray, Liam; Gammon, Marilie D.; Liu, Geoffrey; Bernstein, Leslie; Casson, Alan G.; Risch, Harvey A.; Shaheen, Nicholas J.; Bird, Nigel C.; Reid, Brian J.; Corley, Douglas A.; Hardie, Laura J.; Ye, Weimin; Wu, Anna H.; Zucchelli, Marco; Spector, Tim D.; Hysi, Pirro G.; Vaughan, Thomas L.; Whiteman, David C.; MacGregor, Stuart

doi:10.1093/jnci/djt303

Cited by 88 publications

(81 citation statements)

References 51 publications

(46 reference statements)

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“…Th e overall diagnostic yield was 20% ( 43 ). Single-nucleotide polymorphisms on gene loci, which may confer increased susceptibility to BE development, have recently been described (44)(45)(46)(47).…”

Section: Summary Of Evidencementioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,323

1,412

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Recent population studies suggest that gastroesophageal refl ux disease (GERD) is increasing in prevalence, both in the United States and worldwide ( 1,2 ). Th e diagnosis of GERD is associated with a 10-15% risk of Barrett's esophagus (BE), a change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia (IM). Risk factors associated with the development of BE include long-standing GERD, male gender, central obesity ( 3 ), and age over 50 years ( 4,5 ). Th e goal of a screening and surveillance program for BE is to identify individuals at risk for progression to esophageal adenocarcinoma (EAC), a malignancy that has been increasing in incidence since the 1970s ( 6,7 ).Th e purpose of this guideline is to review the defi nition and epidemiology of BE, available screening modalities for BE detection, rationale and methods for surveillance, and available treatment modalities including medical, endoscopic, and surgical techniques. In order to evaluate the level of evidence and strength of recommendations, we used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system ( 8 ). Th e level of evidence ranged from "high" (implying that further research was unlikely to change the authors' confi dence in the estimate of the eff ect) to "moderate" (further research would be likely to have an impact on the confi dence in the estimate of eff ect) to "low" (further research would be expected to have an important impact on the confi dence in the estimate of the eff ect and would be likely to change the estimate) or "very low" (any estimate of eff ect is very uncertain). Th e strength of a recommendation was graded as "strong" when the desirable eff ects of an intervention clearly outweighed the undesirable eff ects and as "conditional" when there was uncertainty about the tradeoff s. We used meta-analyses or systematic reviews when available, followed by clinical trials and cohort and case-control studies. In order to determine the level Barrett's esophagus (BE) is among the most common conditions encountered by the gastroenterologist. In this document, the American College of Gastroenterology updates its guidance for the best practices in caring for these patients. These guidelines continue to endorse screening of high-risk patients for BE; however, routine screening is limited to men with refl ux symptoms and multiple other risk factors. Acknowledging recent data on the low risk of malignant progression in patients with nondysplastic BE, endoscopic surveillance intervals are attenuated in this population; patients with nondysplastic BE should undergo endoscopic surveillance no more frequently than every 3-5 years. Neither routine use of biomarker panels nor advanced endoscopic imaging techniques (beyond high-defi nition endoscopy) is recommended at this time. Endoscopic ablative therapy is recommended for patients with BE and high-grade dysplasia, as well as T1a esophageal adenocarcinoma. Based on recent level 1 evidence, endoscopic ablative therapy is ...

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Section: Summary Of Evidencementioning

confidence: 99%

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Shaheen

Falk

Iyer

et al. 2016

American Journal of Gastroenterology

1,323

1,412

View full text Add to dashboard Cite

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“…The major hurdle in understanding the mechanisms of the racial disparity regarding BE and EAC lies in the small sample sizes of BE and EAC among other racial/ethnic groups [58]. GWAS in Europe and the USA have shown that the shared polygenic effects due to many genetic variants with a small effect contribute to the development of EAC [59]. Several significant SNPs are associated with FOXP1, BARX1, FOXF1, CRTC1, CDKN2A and TP53 [60,61,62].…”

Section: Esophageal Adenocarcinomamentioning

confidence: 99%

Etiology and Prevention of Esophageal Cancer

Yang

Chen

2016

Gastrointest Tumors

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Background: Esophageal cancer (EC) occurs commonly, especially in Asia, and is the sixth leading cause of cancer deaths worldwide. Recently, great progress has been made in research on the etiology and prevention of EC. Summary: The major risk factors for esophageal squamous cell carcinoma (ESCC) are tobacco smoking and alcohol drinking, which act synergistically. Dietary parameters, including dietary carcinogens and insufficiency of micronutrients, could also be important risk factors in certain areas. A common etiological factor for both EC and some other cancers are low levels of intake of fruits and vegetables. With improvements in diet and drinking water in developing countries, the incidence of ESCC decreased. However, in economically well-developed countries, the incidence of esophageal adenocarcinoma (EAC) has markedly increased in the past 40 years. The major etiological factor for EAC is gastroesophageal reflux, which is also an etiological factor for gastric cardia adenocarcinoma (GCA). In certain areas of China, the occurrence of GCA is closely related to ESCC. Susceptibility genes for EC are starting to be discovered, and this may help to identify high-risk groups that have more need for preventive measures. Mitigation of the risk factors, early detection and treatment of precancerous lesions are effective approaches for prevention. Smoking cessation, avoidance of excessive alcohol, meat and caloric consumption, increasing physical activity and frequent consumption of vegetables and fruits are prudent lifestyle modifications for the prevention of EC as well as other diseases. Key Message: The etiology of EC includes tobacco smoking, alcohol drinking, low levels of intake of fruits and vegetables as well as gastroesophageal reflux and susceptibility genes. Practical Implications: A healthy lifestyle including smoking cessation, increasing physical activity, consumption of vegetables as well as reduction of alcohol intake and caloric consumption are major approaches to the prevention of EC.

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“…In addition, 13 patients (11.2%) with BO/OAC carried germ line mutations in MSR1 , ASCC1 , or CTHRC1 [8] . Ek et al [9] estimated a statistically significant genetic variance explaining BO (array heritability h 2 g = 35%; onesided p = 1 × 10 -9 ) and OAC (h 2 g = 25%; one-sided p = 2 × 10 -7 ). The genetic correlation between BO and OAC was found to be elevated (genetic correlation r g = 1.0).…”

Section: Family History and Genetic Associationsmentioning

confidence: 99%

Risk Factors for Barrett's Oesophagus

Sharma

2016

Gastrointest Tumors

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Background: Barrett's oesophagus (BO) is a premalignant condition associated with the development of oesophageal adenocarcinoma (OAC). Globally, the incidence of OAC is rising. Furthermore, the prognosis regarding the morbidity and mortality of OAC is bleak, with an estimated 5-year survival of 10-15%. Hence, detection of the premalignant phase is paramount. Endoscopy and biopsy sampling is the mainstay of diagnosis. Patients may present with symptoms of gastro-oesophageal reflux disease (GORD) or be completely asymptomatic. Therefore, symptomatology alone is a poor indicator of this condition. Summary: This review highlights the current risk factors associated with the development of BO. Key Message: Primary risk factors for BO include male gender, increased age, a family history of the disease, long-standing GORD, smoking, obesity (specifically determined by the waist-to-hip ratio as opposed to BMI), and Caucasian race. Alcohol consumption and Helicobacter pylori are not associated with the condition. Practical Implications: By ensuring an appropriate understanding of the risk factors, clinicians can discern at-risk patients for endoscopic diagnosis and surveillance.

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Germline Genetic Contributions to Risk for Esophageal Adenocarcinoma, Barrett's Esophagus, and Gastroesophageal Reflux

Abstract: We have demonstrated that risk to BE and EA is influenced by many germline genetic variants of small effect and that shared polygenic effects contribute to risk of these two diseases.

Cited by 88 publications

References 51 publications

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

ACG Clinical Guideline: Diagnosis and Management of Barrett’s Esophagus

Etiology and Prevention of Esophageal Cancer

Risk Factors for Barrett's Oesophagus

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