Tehran University of Medical Sciences Iranian Journal of Public Health 2251-6085 52 9 2023 08 27 2004 2013 Saeid Latifi-Navid Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran Esmat Abdi Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran Saber Zahri Department of Biology, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran Behdad Mostafaiy Department of Statistics, Faculty of Sciences, University of Mohaghegh Ardabili, Ardabil, Iran Abbas Yazdanbod Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran Farhad Pourfarzi Digestive Disease Research Center, Ardabil University of Medical Sciences, Ardabil, Iran 2021 08 21 2021 12 07 Background: Family history of gastric cancer (GC) in first-degree relatives may increase the risk of GC. This study aimed to assess how family history of GC in first-degree relatives really affects the risk of GC in an extremely high-risk population. Methods: A large population-based case-control study was carried out on 1222 incident GC cases and 1235 controls in Ardabil Province-a high-risk area in North-West Iran-to assess the associations of GC family history in first-degree relatives with the risk of GC (2003-2017). Results: GC family history did not significantly associate with the risk of GC overall (ORadj=1.09, 95% CI: 0.80–1.47, P=0.589). It found no significant association of GC family history in a parent, and in a father, mother, and sister separately, with the risk of GC. However, GC risk was significantly associated with a history of GC in a sibling (ORadj=1.61, 95% CI: 1.11–2.35, P=0.013), especially brother (ORadj=2.24, 95% CI: 1.41–3.64, P=0.0008). The risk was greatly increased in subjects with two or more affected brothers (ORadj =5.56, 95% CI: 2.33–14.20, P=0.0002). Conclusion: We did not find a familial tendency to cardia GC and non-cardia GC as well as histopathologic features. Determining the type of first-degree relationships with GC may, therefore, be more important than assessing family history alone for predicting the risk of GC in this high-risk area.   https://ijph.tums.ac.ir/index.php/ijph/article/view/26028 https://ijph.tums.ac.ir/index.php/ijph/article/download/26028/8044