Introduction
Gastric cancer (GC) is a leading cause of cancer-related deaths worldwide, ranking fourth in terms of mortality and fifth in terms of incidence, according to the 2020 GLOBOCAN report (1). Early detection of preneoplastic conditions such as gastric atrophy and intestinal metaplasia is crucial to reduce GC mortality (2). Moreover, its pathogenesis is a multifactorial process that is influenced by environmental and genetic factors. European guidelines (3) suggest shortening the interval of follow-up in patients with a family history. However, it is a weak recommendation with a low quality of evidence, as evidence regarding familiarity for GC and its related preneoplastic conditions is lacking.
Aims & Methods
To evaluate the risk of GC and preneoplastic conditions and lesions, including gastric atrophy, intestinal metaplasia, and dysplasia, in first-degree relatives for GC patients.
We conducted a systematic review and meta-analysis of case-control studies published on MEDLINE (PubMed and Embase) until November 2022. The primary outcome was the risk of GC in first-degree relatives for GC patients. The secondary findings were the risk of preneoplastic conditions and dysplasia in these patients. Two independent reviewers blindly performed the systematic review and data extraction. The disagreements were resolved through discussion. Homogeneity of effects across studies quantified by I2. Odds ratio (OR) and 95% confidence intervals (CIs) were expressed using random effects models.
Results
Of the 1642 studies initially found, 18 studies met the inclusion criteria for GC, and 6 studies were included for preneoplastic conditions. The pooled analysis included a total of 59490 patients for the risk of GC and 4463 patients for the risk of preneoplastic conditions. The results showed a significantly increased risk of GC in first-degree relatives of GC patients (OR = 3.034; 95%CI 2.395 to 3.843; p <.001; I2 85.66%, 95%CI 78.73 to 90.33, p<.001). The risk of gastric atrophy was also significantly increased (OR = 3.812; 95%CI 1.674 to 8.682; p <.001, I2 78,26%, 95%CI 41.41 to 91.93; p = .003). However, the risk of intestinal metaplasia was not significant (OR = 1.207; 95%CI 0.937 to 1.555, p = .15). Furthermore, the risk of gastric dysplasia was found to be significant (OR = 5.480; 95%CI 1.054 to 28.482, p = .043, I2 80.34%, 95%CI 48.18 to 92.55 p = .002).
Conclusion
Our meta-analysis showed that the risk of GC and preneoplastic conditions and lesions, including gastric atrophy and dysplasia, is significantly increased in first-degree relatives for GC patients, even if a significant heterogeneity between studies was found. These findings highlighted the importance of identifying individuals at high risk to facilitate early detection and treatment of preneoplastic conditions, which could potentially reduce the burden of GC.
References
1. Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: a cancer journal for clinicians, 71(3), 209-249.
2. Pimentel-Nunes, P., Libânio, D., Marcos-Pinto, R., Areia, M., Leja, M., Esposito, G., ... & Dinis-Ribeiro, M. (2019). Management of epithelial precancerous conditions and lesions in the stomach (maps II): European Society of gastrointestinal endoscopy (ESGE), European Helicobacter and microbiota Study Group (EHMSG), European Society of pathology (ESP), and Sociedade Portuguesa de Endoscopia Digestiva (SPED) guideline update 2019. Endoscopy, 51(04), 365-388.
3. Yaghoobi, M., Bijarchi, R., & Narod, S. A. (2010). Family history and the risk of gastric cancer. British journal of cancer, 102(2), 237-242.