Epidemiological Scenario of and Gastric Cancer in Chile

Version	Summary	Created by	Modification	Content Size	Created at	Operation
1		Roxana González	--	2044	2024-02-06 17:41:32	\|
2	layout	Jessie Wu	+ 1 word(s)	2045	2024-02-07 01:30:34	\|

This entry is adapted from the peer-reviewed paper 10.3390/ijms25031761

Helicobacter pylori (H. pylori) is a Gram-negative, microaerophilic bacterium that colonizes the gastric mucosa of more than 50% of the world’s population. In 1994, the International Agency for Research on Cancer classified it as a Group I carcinogen. Infection can be acquired in childhood and persist asymptomatically throughout life. H. pylori causes chronic gastritis. This can lead to peptic ulcers as well as premalignant lesions such as atrophic gastritis, intestinal metaplasia, and dysplasia, which can eventually trigger gastric cancer. Atrophic gastritis is the first step in the premalignant cascade and is characterized by the loss of gastric glandular cells, resulting in reduced acid production and an increase in pH levels. Intestinal metaplasia refers to the transformation of the gastric epithelium into an intestinal-type epithelium, which can be complete or incomplete, depending on the presence of goblet cells among the epithelial cells.

gastric cancer Latin American Helicobacter pylori cagA vacA Chile

1. Local Genetic Variants of Helicobacter pylori

Previously, from 63 H. pylori strains isolated from Chilean patients without differentiation of geographical location, the cagA gene and the s1 m1 allelic variants of the vacA gene had a prevalence of 52%, being more common in patients with peptic ulcers than in strains isolated from patients with non-ulcer dyspepsia (26%) (p = 0.035) ^[1]. Similarly, a study of the cagA and vacA genes of H. pylori strains isolated from 50 Chilean patients with gastrointestinal symptoms revealed the presence of cagA in 19 samples (38%). The prevalence of the s1 and s2 signal sequences of vacA was similar, being detected in 16 samples each (32%), and the m2 middle region predominated in 29 samples (58%). In patients where only one vacA genotype was detected, the most frequent was s2 m2, followed by s1 m1 and s1 m2, and one strain was detected with the s2 m1 genotype ^[2]. Studies conducted from 245 H. pylori isolates obtained from biopsies of 79 patients from different places in Chile (Iquique, La Calera, Quillota, Valparaíso, Santiago, Linares, Los Angeles, Temuco, Valdivia, and Punta Arenas) and who suffered from gastrointestinal diseases revealed that the most prevalent vacA variant corresponds to the s1b m1 genotype (72%), followed by s1a m1 (25%), and, sparsely, s2 m2 (3%) ^[3]. The prevalence of these variants showed a differentiated geographical distribution. Patients north of Santiago exclusively carry s1b m1, while patients from Santiago and south of Santiago would carry strains with one or both genotypes (s1a m1 and s1b m1) ^[3].

Another study analyzed 66 isolates of H. pylori obtained from 41 patients in Concepción, who consulted due to suspicions of upper digestive pathology between 2001 and 2002. The presence of cagA, vacA (s and m), and babA2 genes was determined. The results showed the detection of the cagA gene in 24.2% of the clinical isolates analyzed (16/66), while the vacA s1a gene was detected in 42.4% of the samples (28/66), vacA s1b in 21.2% (14/66), vacA s2 in 25.8% (17/66), vacA m1 in 31.8% (21/66), and vacA m2 in 43.9% (29/66). It is worth noting that one isolate (1.5%) was identified that was positive for the babA2 gene, constituting the first record of this genotype in Chile. Furthermore, this clinical isolate also carried the cagA+ and vacA s1a genes that have been linked to severe gastric diseases, and there were five isolates that showed an ulcerogenic profile with the cagA+ and vacA s1 m1 genes ^[4].

On the other hand, the analysis of 78 clinical isolates of H. pylori from biopsy samples of antral mucosa from 100 patients with dyspeptic symptoms in the Maule Region, identified the cagA gene in 94.9% of all isolates (74/78) and the vacA gene in 100% of the isolates (78/78). The s2 and m2 alleles of vacA were the most representative (74.4% and 75.6%, respectively), with an association of 58.1% with respect to cagA-positive isolates. Additionally, it was determined that 48.6% of the cagA-positive strains harbored two or more EPIYA-C motifs, which were associated with more severe pathological findings ^[5].

In this sense, a previous study that involved the isolation of 38 strains from patients with non-ulcer dyspepsia and 25 from individuals with peptic ulcer showed that cagA was present in 60% of the patients with peptic ulcer (15 out of 25) and in 55% of the patients with dyspepsia (21 out of 38). The prevalence of the s1 allelic variant of vacA was similar among strains obtained from ulcers or patients with non-ulcer dyspepsia. However, the cagA+/vacA s1 m1 combination was found more frequently among H. pylori strains from patients with peptic ulcer (52%) than among strains isolated in the other group (26%) (p = 0.035). The authors concluded that the presence of cagA or the s1 vacA allelic variant alone would not have predictive value as a risk marker for serious gastric pathologies in the Chilean population. However, being infected with an H. pylori strain with the cagA+/vacA s1 m1 genotype could be associated with a higher risk of acquiring peptic ulcer disease ^[1].

This suggests that the s1 m1 alleles of the vacA gene and cagA-positive strains are representative in Chilean patients and, given the limited literature, it is possible to infer that these genes are related to more serious gastrointestinal pathologies. Their presence in the population depends on geographical distribution, and it could be hypothesized that strains with these genotypes would be of European ancestry.

2. Epidemiological Retrospective of Helicobacter pylori and Gastric Cancer

While the genotypes present globally, in Latin America, and Chile have been described, it is important to understand the prevalence of H. pylori in Chile and its correlation with a higher risk of gastric disease. One of the first studies to determine the prevalence of H. pylori was conducted on symptomatic and asymptomatic individuals of low socioeconomic status in Santiago and was published in 1993 ^[6]. The endoscopic and histological examination of 111 cases demonstrated changes in the gastric mucosa in 91% of the patients, with the most prevalent conditions being gastritis (71%) and duodenal ulcer (20%). The observed prevalence of H. pylori in biopsies of patients with gastritis was 90%, and for those with duodenal ulcers, it was 100%. In individuals with normal gastric findings, it was 3 out of 10 (30%, p < 0.01) ^[6]. Subsequently, a study that included 190 control individuals and 236 patients with varying degrees of endoscopic esophagitis (55 with gastroesophageal reflux, 81 with erosive esophagitis, and 100 with Barrett’s esophagus) determined a similar prevalence of H. pylori (20–32%) in the gastric antrum of healthy controls and in any group of patients with endoscopic esophagitis ^[7]. No differences were observed in distribution by age and sex, and the infection of H. pylori in the gastric fundus was less than 5% ^[7].

On the other hand, the evaluation of H. pylori in 200 patients with chronic gastritis from the Temuco hospital showed that 82% had H. pylori-like organisms. Additionally, the infection was present in 92.7% of patients with gastric ulcers and in 94.4% of patients with duodenal ulcers ^[8]. The prevalence of H. pylori infection in 276 patients from the Metropolitan Region showed that the bacteria were detected using the urease test in 124 patients (44.9%), and the infection was more prevalent in younger patients (53.8%, between 21 and 60 years) and lower in patients over 60 years (25.6%) ^[9].

The largest study conducted in Chile, reported in 2010, included 5664 symptomatic patients, of which 59.3% presented a normal endoscopic diagnosis, 20% had erosive esophagitis, 8.1% gastric ulcer, 6.4% duodenal ulcer, and 6.2% erosive gastropathy. Of the cases, 78% were infected with H. pylori, and the prevalence of infection was higher in patients with duodenal ulcers (86.6%, p < 0.001), followed by gastric ulcers (81.4%, p = 0.02), erosive gastropathy (79.9%), and erosive esophagitis (77%). The authors concluded that the prevalence of H. pylori infection is high in symptomatic Chilean patients and even higher in those with gastroduodenal ulcers or erosions, while in patients with erosive esophagitis, the incidence is similar to those with a normal endoscopy ^[10].

Moreover, the prevalence of H. pylori infection in 274 pregnant Chilean women from the Biobío Region, and its relationship with gastrointestinal symptoms, showed that 68.6% had H. pylori infection (188 of 274), with no differences between the population with symptoms of dyspepsia, and only 63 women (23%) were negative ^[11]. More recently, an innovative study demonstrated a prevalence of 76.9% for H. pylori and 25.4% for the cagA strain from stool analysis in 160 symptomatic patients from the Coquimbo Region, with no significant differences between genders ^[12]. More recently still, a cross-sectional study conducted between January and December 2018 gathered a total of 229 antral biopsies from dyspeptic patients undergoing endoscopy in the public (n = 143) and private (n = 86) health systems, all from the Araucanía Region, with an observed prevalence of H. pylori of 45.41%, with infection risk showing a higher association with the Mapuche ethnicity (OR = 2.30, CI = 1.14–4.78, p = 0.026) ^[13]. These results were later validated in an independent cohort of 155 cases with similar clinical and demographic characteristics, verifying a prevalence of H. pylori in the general population of 43.2% (67 of 155) and 55.0% (22 of 40) within the Mapuche population ^[14].

Based on all the aforementioned data, the prevalence of H. pylori varies between 20% and 92% (Table 1). Its relationship with an increased risk of gastrointestinal disease has been mentioned; however, the determination of the bacteria has been developed by different methods that in some cases cannot be comparable and vary significantly in the detection percentage. Through an ELISA assay, serum IgG antibodies against H. pylori were determined in 2615 individuals, and the results showed a prevalence of H. pylori of 73.0% (95% CI, 70.0–76.0%), with higher infection in men from 45 to 64 years old, decreasing after 65 years old ^[15]. Using a hierarchical Poisson regression model, the spatial distribution of deaths from gastric cancer between 1985 and 2002 in 333 municipalities was analyzed, classified into low, medium, and high mortality, and showed mortality rates of 11.4, 19.1, and 26.0 per 100,000 inhabitants, respectively. It is noteworthy that the prevalence of H. pylori was higher among residents of places with high mortality from gastric cancer (79.7%; 95% CI, 76.4–82.6) compared to places with low gastric cancer mortality (62.3%; 95% CI, 53.8–70.2; corresponding proportional reporting ratio, 1.3; 95% CI, 1.1–1.5), according to the regression model used ^[15].

Table 1. Prevalence of H. pylori in Chile.

Total Cases	Age (Years)	% Female Group	Diagnostic Tool	Observed Prevalence	Region of Study	Ref.
251	30.5	65.2	Biopsy: microscopy, culture, and urease test	92%	Metropolitan	^[6]
426	45.9	57	Biopsy: microscopy, culture, and urease test	20–32%	Unspecified	^[7]
200	59.5	48.9	Microscopy alone	82%	Araucania	^[8]
276	50.6	70.6	Urease test	44.9%	Metropolitan	^[9]
2615	45	52.1	Serology: IgG ELISA test	73%	Unspecified	^[15]
5664	50.7	73.1	Urease test	78%	Metropolitan	^[10]
100	ND	ND	Biopsy: microscopy, culture, and urease test	78%	Maule	^[5]
274	ND	100	Serology: IgG ELISA test	68.6%	Biobio	^[11]
270	59	36.3	Microscopy alone	49.2%	Metropolitan	^[16]
160	55.6	71.9	Microscopy alone	74.6%	Coquimbo	^[12]
229	50.7	64.2	Urease test	45.4	Araucania	^[13]
485	54.5	63.1	Microscopy alone	30.3%	Araucania	^[17]
155	51.1	66.4	Urease test	43.2%	Araucania	^[14]
1395	62.5	ND	Serology: IgG ELISA test	67% and 63%	Antofagasta and Los Ríos	^[18]

ND: No data.

Another study allowed the evaluation of the difference in the detection of premalignant gastric lesions using the Sydney protocol (n = 124) compared to the conventional endoscopic approach (n = 146). In relation to the result of the biopsies, it was found that 49.2% of the biopsies performed with the Sydney protocol were positive for the presence of H. pylori, in contrast to 20.5% of the biopsies without the protocol (p < 0.001). The authors concluded that the Sydney protocol significantly increases the detection of H. pylori infection and the differential diagnosis of the premalignant cascade compared to the study without a protocol ^[16]. Subsequently, a study considering the population of Temuco conducted on 485 endoscopic biopsies under the OLGA criterion established a prevalence of H. pylori of 30.3% of patients (150 of 485) using methylene blue histological staining and differential Quik staining (Diff-Quik), with a higher incidence in men (60%) than women (40%) (p < 0.001). Additionally, infection with H. pylori was greater in younger groups (45–56 years, p < 0.05), and those patients who were infected with H. pylori had more gastric atrophy and metaplasia than those without infection (p < 0.05) ^[17].

To date, one of the most significant studies corresponds to the comparison of two locations with extreme differences in incidence and mortality associated with gastric cancer. The Epidemiological Investigation of Gastric Malignancies study compared the cities of Antofagasta and Valdivia, with the lowest and highest rates of gastric cancer, respectively. The incidence of H. pylori observed in 700 participants was 67% (95% CI = 63–71) in Antofagasta (lower risk gastric cancer area) and 63% (95% CI = 60–67) in Valdivia (higher risk gastric cancer area). The age-adjusted prevalence was 58% (95% CI = 51–69) in Antofagasta and 56% (95% CI = 49–66) in Valdivia. The seroprevalence of H. pylori was 20% among children < 10 years, 40% among those 10 to 19 years old, 60% among those 20 to 29 years old, and close to or over 80% in those over 30 years old. Therefore, the prevalence of H. pylori infection and its virulence factors was similar in the high- and low-risk areas, but atrophy was more common and occurred at younger ages in the higher-risk areas. Surprisingly, from a multivariate model that combined both sites, age, spicy food consumption, and the presence of cagA were the main risk factors for gastric atrophy, with dietary factors being the most determinant in the rates of gastric atrophy, acting as the dietetic factors most determinant in the rate of atrophy and gastric cancer among the national population ^[18].

References

Faundez, G.; Troncoso, M.; Figueroa, G. cagA and vacA in strains of Helicobacter pylori from ulcer and non-ulcerative dyspepsia patients. BMC Gastroenterol. 2002, 2, 20.
Martínez, A.; González, C.; Kawaguchi, F.; Montoya, R.; Corvalán, A.; Madariaga, J.; Roa, J.; García, A.; Salgado, F.; Solar, H.; et al. Helicobacter pylori: Análisis de cagA y genotipificación de vacA en Chile. Detección de una cepa s2/m1 . Rev. Med Chil 2001, 129, 1147–1153.
Diaz, M.I.; Valdivia, A.; Martinez, P.; Palacios, J.L.; Harris, P.; Novales, J.; Garrido, E.; Valderrama, D.; Shilling, C.; Kirberg, A.; et al. Helicobacter pylori vacA s1a and s1b alleles from clinical isolates from different regions of Chile show a distinct geographic distribution. World J. Gastroenterol. 2005, 11, 6366–6372.
García, A.; Barra, R.; Delgado, C.; Kawaguchi, F.; Trabal, N.; Montenegro, S.; González, C. Genotipificación de aislados clínicos de Helicobacter pylori en base a genes asociados a virulencia cagA, vacA y babA2. Primer aislamiento de una cepa babA2 positiva en pacientes chilenos . Rev. Med Chil 2006, 134, 981–988.
González, I.; Romero, J.; Rodríguez, B.; Llanos, J.; Morales, E.; Figueroa, H.; Perez-Castro, R.; Valdés, E.; Cofre, C.; Rojas, A. High prevalence of virulence-associated genotypes in Helicobacter pylori clinical isolates in the Region del Maule, Chile. Scand. J. Infect. Dis. 2011, 43, 652–655.
Figueroa, G.; Troncoso, M.; Portell, D.P.; Toledo, M.S.; Acuña, R.; Arellano, L. Prevalence of immunoglobulin G antibodies to Helicobacter pylori in Chilean individuals. Eur. J. Clin. Microbiol. Infect. Dis. 1993, 12, 795–797.
Csendes, A.; Smok, G.; Cerda, G.; Burdiles, P.; Mazza, D.; Csendes, P. Prevalence of Helicobacter pylori infection in 190 control subjects and in 236 patients with gastroesophageal reflux, erosive esophagitis or Barrett’s esophagus. Dis. Esophagus 1997, 10, 38–42.
Araya, J.C.; Villaseca, M.A.; Roa, I.; Roa, J.C. Helicobacter pylori y gastritis crónica: Relación entre infección y actividad inflamatoria en población de alto riesgo de cáncer gástrico . Rev. Med Chil 2000, 128, 259–265.
Toledo, H.; Defilippi, C.; Madrid, A.; Defilippi, C.; Vallejos, C.; Cáceres, D.; Venegas, M. Prevalencia de la infección por Helicobacter pylori según ensayo de la ureasa en pacientes derivados a la Unidad de Endoscopía del Hospital Clínico de la Universidad de Chile. Rev. Hosp. Clín Univ. Chile 2007, 18, 189–193.
Ortega, J.P.; Espino, A.; Calvo, B.A.; Verdugo, P.; Pruyas, M.; Nilsen, E.; Villarroel, L.; Padilla, O.; Riquelme, A.; Rollán, A. Infección por Helicobacter pylori en pacientes sintomáticos con patología gastroduodenal benigna: Análisis de 5.664 pacientes . Rev. Med Chil 2010, 138, 529–535.
Poveda, G.F.; Carrillo, K.S.; Monje, M.E.; Cruz, C.A.; Cancino, A.G. Helicobacter pylori infection and gastrointestinal symptoms on Chilean pregnant women. Rev. Assoc. Med Bras. 2014, 60, 306–310.
Wormwood, T.; Parra, Á.; Bresky, G.; Madariaga, J.A.; Häberle, S.; Flores, J.; Bernal, G. Prevalencia de cepas cagA-positivo en la región de Coquimbo, determinada mediante nested-qPCR en muestras fecales . Rev. Med Chil 2018, 146, 596–602.
Oporto, M.; Pavez, M.; Troncoso, C.; Cerda, A.; Hofmann, E.; Sierralta, A.; Rios, E.; Coppelli, L.; Barrientos, L. Prevalence of Infection and Antibiotic Susceptibility of Helicobacter pylori: An Evaluation in Public and Private Health Systems of Southern Chile. Pathogens 2019, 8, 226.
Troncoso, C.; Pavez, M.; Cerda, A.; Oporto, M.; Villarroel, D.; Hofmann, E.; Rios, E.; Sierralta, A.; Copelli, L.; Barrientos, L. MALDI-TOF MS and 16S RNA Identification of Culturable Gastric Microbiota: Variability Associated with the Presence of Helicobacter pylori. Microorganisms 2020, 8, 1763.
Ferreccio, C.; Rollán, A.; Harris, P.R.; Serrano, C.; Gederlini, A.; Margozzini, P.; Gonzalez, C.; Aguilera, X.; Venegas, A.; Jara, A. Gastric cancer is related to early Helicobacter pylori infection in a high-prevalence country. Cancer Epidemiol. Biomark. Prev. 2007, 16, 662–667.
Latorre, G.; Jiménez, M.; Robles, C.; Jensen, E.; Ramos, B.; Fritzsche, M. Aumento de detección de lesiones gástricas premalignas mediante protocolo Sydney en comparación con biopsias no protocolizadas. Gastroenterol. Latinoam. 2016, 27, 207–214.
Bellolio, E.; Riquelme, I.; Riffo-Campos, A.L.; Rueda, C.; Ferreccio, C.; Villaseca, M.; Brebi, P.; Muñoz, S.; Araya, J.C. Assessment of Gastritis and Gastric Cancer Risk in the Chilean Population Using the OLGA System. Pathol. Oncol. Res. 2019, 25, 1135–1142.
Herrero, R.; Heise, K.; Acevedo, J.; Cook, P.; Gonzalez, C.; Gahona, J.; Cortés, R.; Collado, L.; Beltrán, M.E.; Cikutovic, M.; et al. Regional variations in Helicobacter pylori infection, gastric atrophy and gastric cancer risk: The ENIGMA study in Chile. PLoS ONE 2020, 15, e0237515.

© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.

Upload a video for this entry

Information

Subjects: Health Care Sciences & Services

Contributors MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :

Roxana González-Stegmaier

Patricia Aguila-Torres

Franz Villarroel-Espíndola

View Times: 142

Update Date: 07 Feb 2024

Table of Contents

Video Upload Options

Confirm

1. Local Genetic Variants of Helicobacter pylori

2. Epidemiological Retrospective of Helicobacter pylori and Gastric Cancer

References