The utility of serologic tests as biomarkers for Helicobacter pylori-associated precancerous lesions and gastric cancer varies between Latin American countries (original) (raw)
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International Journal of Cancer, 1998
Helicobacter pylori strains possessing the Cag pathogenicity island have been associated with increased gastric inflammation and with duodenal ulcer. In contrast, studies on the association of cagA ؉ H. pylori infections and gastric cancer have shown conflicting results. The aim of our study was to determine whether H. pylori and CagA status are associated with gastric cancer in Mexico. We selected serum samples from 3 geographic areas with gastric cancer mortality rates per 100,000 inhabitants of 2.5 (low risk), 4.5 (medium risk) and 6.4 (high risk). H. pylori infection was determined by the detection of antibodies to H. pylori whole cell antigen by an enzyme-linked immunosorbent assay (ELISA). To study the prevalence of infection with cagA ؉ strains, serum IgG antibodies to CagA were determined by ELISA using a recombinant CagA antigen. Of the 2,775 individuals studied, 1,931 were H. pylori seropositive and 1,710 had antibodies against CagA. The risk for gastric cancer in the 3 populations studied increased proportionally as infection with cagA ؉ strains increased (p F 0.001 for trend). H. pylori infection also showed association with gastric cancer (p F 0.05). Individuals seropositive for CagA, but seronegative for H. pylori whole cell antigen, were more frequent in areas with higher gastric cancer rates (p F 0.01). These results support the possible role of CagA(ϩ) status as predictor of risk for gastric adenocarcinoma in Mexico; this is in agreement with results in European and American populations, but contrary to studies in some Asian countries. Int.
Cancer Science, 2003
The usefulness of serology against CagA of Helicobacter pylori as a biomarker to identify high-risk individuals for non-cardia gastric cancer (ncGC) remains unclear among several ethnic populations with a high prevalence of cagA-positive strains. We investigated ethnic differences of CagA serology in two sets of case-control subjects, Japanese-Brazilians (JB) and non-Japanese Brazilians (NJB). We performed a cross-sectional comparison of IgG antibody titers to CagA (CagA-Ab) and the combination of CagA-Ab with conventional surface antigen (Hp-Ab) in 80 JB and 178 NJB ncGC patients and their controls (160 JB and 178 NJB). The level of CagA-Ab titer in cancer cases was significantly higher in NJB than in JB. The strength of the association between CagA-Ab seropositivity ( + + + +) ( ≥ ≥ ≥ ≥10 U/ml) and ncGC was almost 2-fold higher in NJB than in JB [odds ratio (OR) (95% confidence interval), 4.5 (2.6-7.8) and , respectively]. However, in both JB and NJB, the OR was highest in CagA-Ab( + + + +) subjects with low titer (10-29 U/ml), and decreased inversely with elevating CagA-Ab titer. In addition, the serological status of CagA-Ab( + + + +) and Hp-Ab − − − −) showed a similar close association with ncGC between JB and NJB [5.4 (1.9-15.3) and 5.4 (2.0-15.0), respectively]. These results suggest that although the roles of CagA in the carcinogenic process of ncGC might be different between JB and NJB, the CagA-Ab could be a useful marker for ncGC, independently of ethnicity, particularly in high-risk individuals with the serological status of CagA-Ab( + + + +) with low IgG titer or combined with Hp-Ab( − − − −). (Cancer Sci 2003; 94: 64-69)
Arquivos de gastroenterologia
Gastric cancer is the second most common cause of cancer related death worldwide. Although Helicobacter pylori has been classified as a class I carcinogen, the presence of infection is not a factor that alone is able to lead to gastric cancer, and one of the possible explanations for this is the existence of different strains of H. pylori with different degrees of virulence. To investigate the association between cagA-positive H. pylori and gastric cancer, using polymerase chain reaction (PCR) for the detection of this bacterial strain. Twenty-nine patients with gastric cancer were matched by sex and age (± 5 years) with 58 patients without gastric cancer, submitted to upper gastrointestinal endoscopy. All patients were evaluated for the status of infection by H. pylori (through urease test, histological analysis and PCR for the genes ureA and 16SrRNA) and by cagA-positive strain (through PCR for cagA gene). Evaluating the presence of infection by cagA-positive H. pylori, it was ver...
Cancer Epidemiology Biomarkers & Prevention, 2007
The detection of gastric premalignant lesions, atrophic gastritis, corpus atrophic gastritis, and intestinal metaplasia, using several potential markers was examined in Costa Rica. Depending on the lesion investigated, from a total of 223 dyspeptic patients, 58 (26.0%), 31 (13.9%), or 23 (10.3%) were histologically diagnosed with atrophic gastritis, corpus atrophic gastritis, or intestinal metaplasia, respectively. Sera were used for the measurement of pepsinogen (PG) and Helicobacter pylori CagA antibody (CagA-ab) levels by ELISA, and human genomic DNAs were used for the genotyping of interleukin (IL)-1B (À511 and +3954), IL-10 (À1082 and À592), and IL-1RN intron 2 by PCR and RFLP. Multivariate analysis was done adjusting for sex, age, and H. pylori seropositivity. Low PG levels (L-PG; PG I V70 Mg/L + PG I/II V3), very low PG levels (VL-PG; PG I V30 Mg/L + PG I/II V2), and CagA-ab were individually associated with all premalignant lesions whereas IL-1B +3954T-carrier and IL-1RN homozygous 2 allele were associated with intestinal metaplasia. VL-PG, for corpus atrophic gastritis detection, was the single marker with the highest combination of test characteristics, sensitivity (77.4%), specificity (80.7%), positive predictive value (39.3%), negative predictive value (95.7%), and seropositivity rate (27.4%), expected to improve after periodic measurements. Combined examinations of VL-PG and CagA-ab improved the specificity (92.7%) and positive predictive value (62.2%), with similar sensitivity (74.2%) and negative predictive value (95.7%). In conclusion, corpus atrophic gastritis detection with periodic measurements of serum PG, alone or in combination with CagA-ab status, to identify high gastric cancer risk, seems to be the method best suited for mass screening in Costa Rica.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2002
Incidence and mortality rates for gastric cancer in rural People's Republic of China differ greatly over short distances. In Shandong Province, we studied asymptomatic adult subjects from Bei Duan village (n = 196) in Linqu County (a high-risk area for gastric cancer) and from Shi Huang village (n = 192) in Cangshan County (a low-risk area for gastric cancer). The prevalence of advanced precancerous gastric lesions (APGL) was assessed by microscopic examination of endoscopic stomach biopsies. ELISAs were used to detect serum IgG to Helicobacter pylori whole-cell antigen and to the CagA protein. A logistic regression model was used to quantify the role of the two H. pylori seromarkers in explaining the differences in prevalence of APGL between the two villages after adjusting for age and sex. The prevalence of APGL was much greater in Bei Duan than in Shi Huang. Although H. pylori seroprevalence by the whole-cell ELISA was similar in the two populations, seroprevalence of CagA wa...
American Journal of Gastroenterology, 2011
There are no established predictive markers of progression of gastric preneoplastic lesions. The aim of this study was to analyze the relationship between Helicobacter pylori cagA and vacA genotypes and progression of gastric preneoplastic lesions. METHODS: This was a follow-up study that carried out in a province of Spain with a high risk of gastric cancer. A total of 312 patients who underwent upper endoscopy with gastric biopsy in 1988-1994 with diagnoses of normal mucosa, non-atrophic gastritis (NAG), non-metaplastic multifocal atrophic gastritis (MAG), and complete or incomplete intestinal metaplasia (IM), and who accepted to undergo a new biopsy during 2005-2007 or had an end point during follow-up, were included in this study. Detection and characterization of H. pylori cagA and vacA genotypes was performed directly in baseline paraffi n-embedded gastric biopsy specimens by PCR followed by reverse hybridization onto a line probe assay. Inter-and intra-observer variability of histological diagnosis was assessed. Analysis was done using unconditional logistic regression. RESULTS: The mean age of patients was 48.5 years (45 % males) and the mean of follow-up was 12.8 years. H. pylori strains harboring cagA , vacA s1, and vacA m1 genotypes were more frequently found in patients with more advanced gastric preneoplastic lesions. Infection with cagA-positive, vacA s1, and vacA m1 strains was associated with progression of gastric preneoplastic lesions (multivariate odds ratio (OR) = 2.28, 95 % confi dence interval (CI) 1.13-4.58; OR = 2.90, 95 % CI 1.38-6.13; and OR = 3.38, 95 % CI 1.34-8.53, respectively). Infection with strains that are simultaneously cagA positive and vacA s1 / m1 was associated with progression of gastric precancerous lesions with an OR of 4.80 (95 % CI 1.71-13.5) in relation to those infected with cagA-negative / vacA s2 / m2 strains. CONCLUSIONS: H. pylori genotyping may be useful for the identifi cation of patients at high risk of progression of gastric preneoplastic lesions and who need more intensive surveillance.
2013
Infection with Helicobacter pylori cytotoxin-associated gene A (CagA)-positive strains is associated with the development of gastric cancer (GC). However, some reports have failed to demonstrate an increased frequency of CagA antibodies in GC patients. This study evaluated the response of IgG antibody and subclasses IgG1 and IgG2 against both CagA and H. pylori membrane antigens in patients with pre-cancerous lesions and cases with GC. A total of 137 patients with a positive serum IgG response to H. pylori were selected: 46 with intestinal metaplasia, 41 with gastric adenocarcinoma and 50 with non-atrophic gastritis (NAG) considered as controls. The response of total IgG, IgG1 and IgG2 was investigated by immunoblot and ELISA using an in-house recombinant CagA and membrane antigens from a local strain, and possible associations were estimated using a logistic regression model. Compared with NAG patients, GC patients showed a higher frequency of IgG2 CagA antibodies (55.2 vs 15.4 %, P50.001), but a lower frequency (80.5 vs 96.0 %, P50.021) and diminished levels of IgG2 H. pylori antibodies [12.5 vs 21.9 ELISA units (EU), P50.007]. GC patients also presented lower levels of CagA (32.6 vs 42.4 EU, P50.004) and H. pylori total IgG (33.7 vs 38.7 EU, P50.029). GC was associated with a positive IgG2 CagA response [odds ratio (OR)53.74, 95 % confidence interval (CI) 1.81-5.37; P50.002] and with a low titre of total IgG CagA antibodies (OR52.18, 95 % CI 1.35-2.69; P50.006). These results suggest that the IgG2 response to CagA could be used as a novel serological marker to identify patients with H. pylori-associated GC.
Japanese journal of cancer research: Gann
Helicobacter pylori (H. pylori) infection is considered a cause of gastric cancer (GC), though evidence for this association is scarce in high-risk areas. Possible case control and/or ethnic differences were investigated as to the presence of H. pylori and its immunogloblin G antibody titer in the multi-ethnic city of São Paulo, where the incidence of GC is relatively high. We performed a cross-sectional comparison of antibody titers to H. pylori in Japanese Brazilian, and non-Japanese Brazilian GC patients and their controls. Japanese Brazilian patients were matched by age, sex and ethnicity with two controls, while non-Japanese Brazilian patients were matched as above with one control. Among Japanese Brazilians, 59 of 93 (63.4%) patients with GC and 127 of 186 (68.3%) controls were positive for H. pylori-specific antibody (odds ratio (OR) = = = =0.80, 95% confidence interval (CI) = = = =0.47-1.36), while among non-Japanese Brazilians, 171 of 228 patients with GC (75.7%) and 178 of 226 controls (78.8%) were positive (OR = = = =0.84, 95%CI = = = =0.54-1.30). The median serum antibody titer was lower in cases than in controls in both ethnic groups. A high titer (H. pylori titer ≥ ≥ ≥ ≥50) was associated with less likelihood of GC for both ethnic groups (for Japanese Brazilians, OR = = = =0.39, 95%CI = = = =0.16-0.92; for non-Japanese Brazilians, OR = = = =0.56, 95%CI = = = =0.31-1.02). The high titer can be regarded as a sign of the necessity of eradication, and low titer is regarded as a sign of the necessity of close screening for GC in both ethnic groups, because extended atrophy may cause spontaneous disappearance of H. pylori from the stomach.
Cancer Science, 2001
Helicobacter pylori (H. pylori) infection is considered a cause of gastric cancer (GC), though evidence for this association is scarce in high-risk areas. Possible case control and/or ethnic differences were investigated as to the presence of H. pylori and its immunogloblin G antibody titer in the multi-ethnic city of São Paulo, where the incidence of GC is relatively high. We performed a cross-sectional comparison of antibody titers to H. pylori in Japanese Brazilian, and non-Japanese Brazilian GC patients and their controls. Japanese Brazilian patients were matched by age, sex and ethnicity with two controls, while non-Japanese Brazilian patients were matched as above with one control. Among Japanese Brazilians, 59 of 93 (63.4%) patients with GC and 127 of 186 (68.3%) controls were positive for H. pylori-specific antibody (odds ratio (OR) = = = =0.80, 95% confidence interval (CI) = = = =0.47-1.36), while among non-Japanese Brazilians, 171 of 228 patients with GC (75.7%) and 178 of 226 controls (78.8%) were positive (OR = = = =0.84, 95%CI = = = =0.54-1.30). The median serum antibody titer was lower in cases than in controls in both ethnic groups. A high titer (H. pylori titer ≥ ≥ ≥ ≥50) was associated with less likelihood of GC for both ethnic groups (for Japanese Brazilians, OR = = = =0.39, 95%CI = = = =0.16-0.92; for non-Japanese Brazilians, OR = = = =0.56, 95%CI = = = =0.31-1.02). The high titer can be regarded as a sign of the necessity of eradication, and low titer is regarded as a sign of the necessity of close screening for GC in both ethnic groups, because extended atrophy may cause spontaneous disappearance of H. pylori from the stomach.
Cancer Epidemiology Biomarkers & Prevention, 2011
Background: Helicobacter pylori infection is a risk factor for the development of gastric cancer, and the bacterial oncoprotein CagA contributes to gastric carcinogenesis. Methods: We analyzed H. pylori isolates from persons in Colombia and observed that there was marked variation among strains in levels of CagA expression. To elucidate the basis for this variation, we analyzed sequences upstream from the CagA translational initiation site in each strain. Results: A DNA motif (AATAAGATA) upstream of the translational initiation site of CagA was associated with high levels of CagA expression. Experimental studies showed that this motif was necessary but not sufficient for high-level CagA expression. H. pylori strains from a region of Colombia with high gastric cancer rates expressed higher levels of CagA than did strains from a region with lower gastric cancer rates, and Colombian strains of European phylogeographic origin expressed higher levels of CagA than did strains of African origin. Histopathologic analysis of gastric biopsy specimens revealed that strains expressing high levels of CagA or containing the AATAAGATA motif were associated with more advanced precancerous lesions than those found in persons infected with strains expressing low levels of CagA or lacking the AATAAGATA motif. Conclusions: CagA expression varies greatly among H. pylori strains. The DNA motif identified in this study is associated with high levels of CagA expression, and may be a useful biomarker to predict gastric cancer risk. Impact: These findings help to explain why some persons infected with cagA-positive H. pylori develop gastric cancer and others do not. Cancer Epidemiol Biomarkers Prev; 20(10); 2237-49. Ó2011 AACR.