Gastric cancer (GC) is the third most common cancer in Peru and the second most common cause of cancer deaths in the world [1-2]. Prevalence of precancerous gastric lesions and risk of developing GC is higher in relatives of patients with cancer [3]. Helicobacter pylori (H. pylori) is present in 50% of the world population [4], and infected patients have a higher risk of developing chronic gastritis (CG), atrophy, hypochloridria, and cancer of the distal and middle (non-cardia) part of the stomach [3,5]. Some strains of H. pylori are carriers of virulence genes and appear to have a greater carcinogenic potential [6]. Exposure to the same strains of H. pylori in relatives, and the fact that relatives share genes associated with predisposition to develop cancer in the presence of H. pylori infection, would indicate that first-degree relatives of patients with GC who are living in the same home require a more intense follow-up [6,5]. However, there is no information on the prevalence of H. pylori infection in relatives of patients with GC in Peru. The objective of the present study was to evaluate the relationship between the presence of H. pylori infection in Peruvian patients with GC and their relatives.

We included 61 patients domiciled in the Metropolitan Lima who came for diagnosis or screening to the National Institute of Neoplastic Diseases (INEN) from 2015 to 2018. Gastric sections were stored at -80°C. A total of 171 family members living in the same home were invited to have a urease breath test for the detection of H. pylori and absence of antibiotic treatment in the 2 previous weeks was requested (Figure 1).

A descriptive analysis was performed through frequencies, percentages and summary measures. We used Pearson χ2 or Fisher’s exact tests to compare frequencies between groups, and. The statistical software IBM SPSS v.25 was used, and a value of p <0.05 was considered statistically significant.

A total of 61 patients with gastric tissue samples (22 gastroscopy and 39 gastric resections) were included, 45 (73.8%) with GC (adenocarcinoma histology) and 16 (26.2%) without GC (chronic gastritis) (Table 1).

We found that the prevalence of infection in the relatives of the evaluated patients was 60.2%, however, a higher prevalence of H. pylori infection was not found in relatives of patients with GC, nor in relatives of patients with infected gastric tissue nor in relatives of patients with co-diagnosis of gastric metaplasia. This absence of association is probably due to the high prevalence of H. pylori infection in our population.

Different studies find that relatives of patients with GC have a higher risk of also developing the malignancy. Palli et al. evaluated 1016 patients with GC and 1623 controls without GC through questionnaires in Italy, and found that a maternal history of GC is the most significant contributory risk factor for GC in children. This association may be due to the fact that autosomal recessive genes with higher penetrance can be transmitted from mother to child, however it can also explain why mothers have prolonged contact with their children and share exposure to environmental agents such as H. pylori [10]. This last theory coincides with the finding that the risk of developing GC is higher in patients infected with H. pylori at an earlier age [3, 6, 11]. Czene et al. evaluated 9.6 million people included in the Swedish database that assesses the impact of genetic and environmental components on 15 common cancers. The study showed that environmental effect such as H. pylori infection, produce an increase in susceptibility to GC, due to the high correlation rate between spouses and a high correlation between siblings who shared childhood due to a close age range, while the genetic effect was very low [12].

Other studies find that prevalence of H. pylori infection is higher among relatives of GC patients and infection rates appears to be higher in family members with co-habitance during childhood like siblings. Thus, Chang et al. analyzed a total of 726 subjects, including 300 relatives of 300 patients with GC and 426 controls. They found that family members of patients with GC had a higher prevalence of H. pylori infection than controls (75.3% vs. 60.1%) evaluated by a high gastrointestinal endoscopic examination and urease test.

Individuals with a GC sibling (88.9%) or those with >1 GC family members (85.7%) had higher H. pylori infection rates than having a GC parent (64- 75%) [6]. Brenner et al. evaluated a total of 1351 people who participated in the German Health and Nutrition Survey, and found that the sero-prevalence of antibodies against H. pylori was much higher among children of patients with GC than in controls (69% vs 44%). Family history and H. pylori infection were associated with an increased risk of GC and the risk was higher in the presence of infection with cagA- positive H. pylori strain [11]. Finally, additive effect of infection and heritage was described by Shin and et al. who analyzed 428 patients with GC and 368 controls. They found that the risk of developing the malignancy was 3 times higher in those who had first degree relatives with GC. This effect was greater in the young group with H. pylori infection (5-fold risk increase) [13].

Different studies have evaluated the process in which H. pylori increases the GC risk in relatives of patients with GC. El-Omar et al. evaluated a total of 100 first-degree relatives of 40 patients with non-cardia GC, and found that relatives of patients with GC and coinfection with H. pylori (64%) have a higher prevalence of precancerous anomalies such as hypochlorhydria and atrophic gastritis [3]. Jablonska and Chlumska evaluated 108 first-degree relatives of patients with non-cardia GC patients and 73 controls with mild dyspepsia without relatives with cancer. They found that although the prevalence of infection was similar in relatives of patients with or without cancer, there was a much higher prevalence of intestinal atrophy and metaplasia in relatives of patients with GC. The eradication of H. pylori was associated with a reduction in the prevalence of atrophic gastritis [14]. Azuma et al. examined H. pylori infection and the HLA-DQA1 genotype in 82 patients with gastric adenocarcinoma and 167 unrelated controls. They found that the combination of absence of allele DQA1*O102 and H. pylori infection was associated with atrophic gastritis and intestinal type gastric adenocarcinoma. The analysis of serum pepsinogen indicated that its levels would mediate the development of atrophic gastritis [15]. A deficiency of our study is that the detection of H. pylori infection in relatives was carried out through the breath or urease test and not by anatomopathological study, as was performed in the patients. However, different studies indicate that the sensitivity and specificity of this non-invasive test is comparable to that of the pathological study [16].

These findings would suggest that the risk factors observed in low prevalence populations such as those described in European and Asian populations are different from that observed in populations of high prevalence of H. pylori infection such as Peru. In conclusion, H. Pylori infection rates in GC patients and their relatives are high. However, they were not related.

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