Abstract

Simple SummaryResearch is still required to establish the relationship between family history (FH) and gastric cancer (GC) in relation to different histological types and anatomical sites. The present work aimed to examine the influence of first-degree FH on the risk of GC, also according to the GC location and histological type, including 5946 cases and 12,776 controls from 17 studies of 11 countries in three continents participating in the Stomach Cancer Pooling (StoP) Project consortium. This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype.Although there is a clear relationship between family history (FH) and the risk of gastric cancer (GC), quantification is still needed in relation to different histological types and anatomical sites, and in strata of covariates. The objective was to analyze the risk of GC according to first-degree FH in a uniquely large epidemiological consortium of GC. This investigation includes 5946 cases and 12,776 controls from 17 studies of the Stomach Cancer Pooling (StoP) Project consortium. Summary odds ratios (OR) and the corresponding 95% confidence intervals (CIs) were calculated by pooling study-specific ORs using fixed-effect model meta-analysis techniques. Stratified analyses were carried out by sex, age, tumor location and histological type, smoking habit, socioeconomic status, alcohol intake and fruit consumption. The pooled OR for GC was 1.84 (95% CI: 1.64–2.04; I2 = 6.1%, P heterogeneity = 0.383) in subjects with vs. those without first-degree relatives with GC. No significant differences were observed among subgroups of sex, age, geographic area or study period. Associations tended to be stronger for non-cardia (OR = 1.82; 95% CI: 1.59–2.05 for subjects with FH) than for cardia GC (OR = 1.38; 95% CI: 0.98–1.77), and for the intestinal (OR = 1.92; 95% CI: 1.62–2.23) than for the diffuse histotype (OR = 1.62; 95% CI: 1.28–1.96). This analysis confirms the effect of FH on the risk of GC, reporting an approximately doubled risk, and provides further quantification of the risk of GC according to the subsite and histotype. Considering these findings, accounting for the presence of FH to carry out correct prevention and diagnosis measures is of the utmost importance.

Highlights

  • Gastric cancer (GC) is the fifth leading cause of cancer by incidence and the third leading cause of cancer death in both sexes worldwide

  • Of the 2030 intestinal gastric cancer (GC) cases, 365 (18.0%) had a first-degree family history (FH) of GC, yielding a pooled odds ratios (OR) of 1.92

  • Modest higher differences were observedthan acof cardia in subjects with a positive of gastric cancer, whereas no relevant differcording to the type of controls

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Summary

Introduction

Gastric cancer (GC) is the fifth leading cause of cancer by incidence and the third leading cause of cancer death in both sexes worldwide. The most accepted model of human gastric carcinogenesis is a multistage model in which both environmental and genetic factors are involved [2]. Various studies have investigated the role of FH in relation to GC, often reporting relative risks around or over two for subjects with a positive FH of GC [4]. Such a strong association may be explained, besides the genetic component, by environmental exposures—including smoking habits, diet and Helicobacter pylori infection—shared by family members

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