zos from the Americas (of mixed Asian and European ancestry) harbor HpEurope strains.51 The low diversity of Amerindian strains may be linked to their apparent tendency to disappear when colonizing non-Amerindian hosts. In Colombia, inhabitants of the high-altitude Andes Moun- tains have very high incidence rates of gastric cancer compared to inhabitants of the Pacific coast. Both populations have simi- larly high prevalence of H. pylori infection. People living in the mountains are mostly mestizos (of Amerindian descent with European admixture), whereas people living on the Pacific coast are predominantly mulattos (mixed African and European an- cestry). The prevalence of cagA+ vacA s1m1 H. pylori strains in the high risk region is only slightly lower than in the low-risk region.62 Using MLST of seven housekeeping genes, we ana- lyzed cagA+ vacA s1m1 strains from both regions of Colombia and compared them to 380 reference strains.63 All strains of the high risk region (Andes Mountains) were classified as hpEurope (n=35), while among strains from the Pacific coast, 34.5% (n=10) were classified as hpEurope, and the remaining 65.5% (n=19) were classified as hpAfrica1 (3 hspSAfrica, 16 hspWAfrica) (Fig. 2). In this study, strains of European ancestry were associated with more advanced precancerous gastric lesions and greater Fig. 2. Phylogeography of H. pylori . Neighbor-joining tree of 64 cagA+ vacA s1m1 Colombian H. pylori isolates from the high-risk (black circles) and low-risk (open circles) regions, along with 380 reference strains that were previously classified into distinct ancestral haplogroups. Branches are drawn to scale to represent evolution- ary distance. The colors of the branches represent the classification of strains into distinct populations (From de Sablet T, et al. Gut 2011;60:1189-1195, with permission).63 Correa P, et al: Evolutionary History of the Helicobacter pylori Genome 25 oxidative damage in gastric mucosa than strains of African ancestry.63 Known differences in gastric cancer rates may, at least partially, be explained by H. pylori genotypes: high rates in mestizos colonized with more virulent hpEurope strains, as documented in the Colombian Andes Mountains, and low rates in African descendents colonized with the less virulent hspAfri- ca1 strains, as documented in dwellers of the Colombian Pacific coast. In the United States, African Americans have gastric cancer rates approximately twice those of Caucasians.64 This phenom- enon is probably not related to H. pylori genotypes but more related to the prevalence of H. pylori infection in these two eth- nic groups, approximately double in African Americans than in Caucasians.65 Gastric cancer rates in U.S. African Americans are much lower than those of mestizos in Latin America. SECULAR (CENTURIES OLD) TRENDS OF GASTRIC CAN- CER: TWO EPIDEMICS? In epidemiologic terms, an epidemic is defined as an unex- pected increase in the frequency of a disease. Chronologically, epidemics display a bell-shaped curve: an ascending portion, a plateau and descending portion. Sonnenberg66,67 has analyzed time trends of mortality from peptic ulcer and gastric cancer in several countries in terms of their birth cohort pattern. The rates rose in generations born during the 18th century until the mid- 19th century and then have declined in all subsequent genera- tions. He links the decline of mortality rates to the decreasing prevalence of H. pylori infection in the general population. But, in his words, the sudden increase in mortality for these H. pylori related a disease within a relatively short time during the 19th century remains an enigma. It might be that the enigma is re- lated to the secular evolution of the H. pylori genome, with the acquisition of the cag PAI, which occurred both in Asia and the West.44 Sonnenberg’s graphs also show that the steady decline in cancer rates stops for cohorts born around the third decade of the twentieth century, for which increasing rates are observed. This “second” epidemic is driven by younger persons and has previously been detected in Spain and the United States.68,69 The causes of this apparently incipient epidemic are unknown. There is no evidence suggesting that a recent evolution of the H. py- lori genome has taken place. The generalized abuse of antacid medications is a phenomenon that preceded this new epidemic, but a causal link to the new epidemic has not been established. EPILOGUE The co-evolution of Homo sapiens and H. pylori throughout millennia may be coming to an end, especially in affluent soci- eties in which marked improvements in home and food sanita- tion have taken place and antibiotics may be abused to treat minor or to “prevent” infections. The prevalence of the infection