Helicobacter pylori (Hp) colonizes the human stomach and induces acute gastritis, peptic ulcer disease, atrophic gastritis, and gastric adenocarcinoma. increased virulence in Hp isolates derives from harboring the cag (cytotoxin-associated genes) pathogenicity island (cagpAi). We analyzed the microvariants in cagpAi genes with the hypothesis that they may play an important role in determining Hp virulence. We tested DnAs from cagA positive patients HP isolates; a total of 74 patients with chronic gastritis (cG, n = 37), intestinal metaplasia (IM, N = 21) or gastric cancer (GC, N = 16) from Mexico and Colombia. We selected 520 non-synonymous variants with at least 7.5% frequency in the original sequence outputs or with a minimum of 5 isolates with minor allele. After adjustment for multiple comparisons, no variants were statistically significantly associated with IM or GC. However, 19 non-synonymous showed conventional P-values < 0.05 comparing the frequency of the alleles between the isolates from subjects with gastritis and isolates from subjects with IM or GC; 12 of these showed a significant correlation with the severity of the disease. The present study revealed that several cagpAi genes from Latin American Western Hp strains contains a number of non-synonymous variants in relatively high frequencies which could influence on the clinical outcome. However, none of the associations remained statistically significant after adjustment for multiple comparison.Gastric cancer has the third highest mortality rate and the fifth highest incidence worldwide 1 . The two regions of the world with highest mortality rate for gastric cancer are Asia and Latin America accounting for almost two thirds of all gastric cancer deaths 2 . Within the US, ethnic minorities, e.g., Asians, Blacks, Hispanics and Native Americans, experience an incidence almost twice as high as non-Hispanic Whites 3 . Some Asian countries, such as Japan, have nation-wide screening programs for early detection of gastric cancer, whereas most other high-risk countries, such as Latin American countries, do not have such programs, nor does the US for ethnic minorities 4-6 . Although Helicobacter pylori (HP) is an established cause of gastric cancer 7 , eradication of HP in general asymptomatic populations has not been advised, because of the large number of persons already infected in high risk populations (>90%), high reinfection rates in endemic areas 8 , antibiotic resistance, high cost of the treatment 9 and the increased risk of esophageal cancer associated with HP-negative/eradicated individuals 10-12 . Thus, new strategies for gastric cancer prevention are warranted and may help reduce health disparities, mainly in the most affected and underdeveloped regions of the world 13 . All considered identification of new HP variants potentially useful to predict gastric cancer risk will be invaluable not only for vaccine development, but also to target antibiotic treatment to high-risk individuals.HP has a remarkably high level of genetic diversity due to rec...