The objective of this systematic review is to assess the impact of migration on the risk of developing gastric cancer.

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Review title The effect of migration on gastric cancer risk: A systematic review protocol Reviewers Haejin In, MD, MBA, MPH 1 Marisa Langdon-Embry, MS 2 1 Albert Einstein College of Medicine, haejin.in@einstein.yu.edu 2 Albert Einstein College of Medicine, marisa.langdon-embry@einstein.yu.edu Center conducting the review Albert Einstein College of Medicine Review question/objective The objective of this systematic review is to assess the impact of migration on the risk of developing gastric cancer. More specifically, the objectives are to identify: The effects of immigration patterns, including number of years living in the US and age at migration, birthplace and immigration generation on the incidence of gastric cancer in the United States. Background Epidemiological studies have shown that immigrants who travel from high- to low-prevalence countries maintain the same elevated risk from the country they originally emigrated from (Langell and Mulvihill, 2013). However, descendents of immigrants who are born in countries with low incidence tend to have similar prevalence as local people of comparable ethnic origin. This indicates that environmental exposures during childhood may influence the development of gastric cancer. Genetic susceptibility and similar genetic compositions among people of the same ethnic origins may also influence gastric cancer risk and could help explain why different ethnic groups have different rates of gastric cancer in the same geographical areas. However, the effect of immigration and acculturation has never been systematically reviewed and is not widely considered in the literature as being a prominent risk factor for gastric cancer. Inclusion criteria Types of participants This review will consider studies that look at cancer incidence for people who have lived in more than one country. Types of intervention(s)/phenomena of interest The review will consider studies that evaluate birthplace, migration patterns and immigration generation Page 1

The Effect of Migration on Risk of Gastric Cancer: Systematic Review Protocol differences that may influence the risk of gastric cancer. Types of outcomes Only studies that report gastric cancer incidence as the primary outcome will be included for review. Secondary outcomes will include tumor location, age at diagnosis and stage at diagnosis. Types of studies This review will consider both experimental and epidemiological study designs including prospective and retrospective cohort studies, case-control studies, clinical trials, randomized control trials, cross-sectional studies, nested case-control studies, experimental studies, quasi-experimental studies, ecological studies for inclusion. Summary of Inclusion/Exclusion: Inclusion: Cohort studies, case-control studies, clinical trials, randomized control trials, cross-sectional studies, nested case-control studies, experimental studies, quasi-experimental studies, ecological studies Adenocarcinoma histology Studies published in English up to July 31, 2015 Human participants Studies addressing at least one risk factor for gastric cancer Risk factors preceding gastric cancer diagnosis Diagnosis of gastric cancer determined as outcome (gastric cancer incidence) Reporting of risk estimates (e.g. RR or OR) and/or presentation of data necessary to calculate risk estimates Exclusion Studies of mortality rather than incidence Editorials, commentaries, case-reports, letters, practice guidelines or news Studies that do not report data specifically for stomach/gastric cancer (e.g. studies of the digestive tract, without specific anatomic identification) Studies with no risk estimate Secondary gastric cancer Familial genetic syndromes, including hereditary diffuse gastric cancer, Peutz-Jegher s Syndrome, Familial adenomatous Polyposis, hereditary non-polyposis colorectal cancer, Li-Fraumeni syndrome Prior diagnosis that is already known to require endoscopic surveillance (Barretts esophagus, esophageal or gastric adenoma, gastric ulcer, chronic atrophic gastritis, gastric atrophy, etc) Any biomarkers or tests that require a new invasive procedure or laboratory test for screening purposes Search strategy The search strategy aims to find both published and unpublished studies. A three-step search strategy Page 2

will be utilized in this review. An initial limited search of PubMed and EMBASE will be undertaken followed by analysis of the text words contained in the title and abstract, and of the index terms used to describe article. A second search using all identified keywords and index terms will then be undertaken across all included databases. Thirdly, the reference list of all identified reports and articles will be searched for additional studies. Studies published in English will be considered for inclusion in this review. Studies published from inception to July 31st, 2015 will be considered for inclusion in this review. The databases to be searched include: -PubMed -Medline/Ovid -Embase -Web of Science -Cochrane Initial keywords to be used will be: [(immigration) OR (migration) OR (birthplace) OR (geograph*) (country of origin)] AND [(stomach) OR (gastric)] AND [(neoplasm) OR (cancer) OR (tumor) OR (carcinoma) OR (malignancy)] AND [(risk) OR (cause) OR (association) ] AND [(cohort) OR (case-control) OR (ecological study) OR (clinical trial) OR (randomized control trial) OR (RCT) OR (cross-sectional) OR (experimental study) OR (quasi-experimental)] Assessment of methodological quality Quantitative papers selected for retrieval will be assessed by two independent reviewers for methodological validity prior to inclusion in the review using standardized critical appraisal instruments from the Joanna Briggs Institute Meta Analysis of Statistics Assessment and Review Instrument (JBI-MAStARI) (Appendix I). Any disagreements that arise between the reviewers will be resolved through discussion, or with a third reviewer. Data collection Quantitative data will be extracted from papers included in the review using the standardized data extraction tool from JBI-MAStARI (Appendix II). The data extracted will include specific details about the interventions, populations, study methods and outcomes of significance, including: Authors Year of publication Geographical location Study type Number of participants (e.g. cases, controls, cohort size) Risk factors assessed (e.g. migration, country of origin, age at migration, immigration generation) Tumor location (GE junction or cardia/body or antrum/ diffuse (linitis plastica)/ other) Age at presentation Page 3

The Effect of Migration on Risk of Gastric Cancer: Systematic Review Protocol Stage at diagnosis Sex distribution Measure of association (e.g. adjusted RR/OR/HR) and 95% confidence intervals Confounding variables adjusted for Data synthesis Quantitative papers will, where possible be pooled in statistical meta-analysis using JBI-MAStARI. All results will be subject to double data entry. Effect sizes expressed as odds ratio (for categorical data) and weighted mean differences (for continuous data) and their 95% confidence intervals will be calculated for analysis. Heterogeneity will be assessed statistically using the standard Chi-square and also explored using subgroup analyses based on the different quantitative study designs included in this review. There may not be enough published data to conduct a thorough meta-analysis. Where statistical pooling is not possible the findings will be presented in narrative form including tables and figures to aid in data presentation where appropriate. Conflicts of interest There are no conflicts of interest. References 1. Langell JT, Mulvihill SJ (2013). Gastric Adenocarcinoma and Other Gastric Neoplasms (Except Gastrointestinal Stromal Tumors). In: Zinner MJ, Ashley SW(eds), Maingot's Abdominal Operations, 12 ed., Vol 1, McGraw-Hill, New York, pp 463-89. Page 4

Appendix I: Appraisal instruments is a test message Page 5

The Effect of Migration on Risk of Gastric Cancer: Systematic Review Protocol Appendix II: Data extraction instruments MAStARI data extraction instrument Page 6

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