Gastric Cancer: Two Epidemics?

Excerpt

The recent report by Sonnenberg [1] examines the time trends in gastric cancer and may reflect two epidemics, defined as an unexpected rise in the frequency of a disease. The report calls attention to the “enigma” of the rise in mortality rates from gastric cancer and peptic ulcer in cohorts born after the second half of the eighteenth century. Although the causes of this rise are unknown, it is pertinent to explore the possible link between the secular trends in gastric cancer incidence and the secular trends in the genome of Helicobacter pylori, the most prominent cause of gastric cancer. The bacterium is well known for its propensity to genetic recombination. The more virulent strains are characterized by the presence of a pathogenicity island (PAI), a cluster of about 40 genes containing the cagA gene and genes encoding components of a Type IV secretion system which injects the CagA protein into the cytoplasm of the gastric epithelial cells. The island is acquired after recombination with other bacteria, leading to the importation of an insertion sequence IS605 into the genome of H. pylori [2]. That insertion may contain several DNA sequences and result in strains of several degrees of virulence. The complete PAI insertion characterizes the more virulent strains (cagA positive), linked to peptic ulcer and gastric cancer. Another indication of the impact of secular changes in the H. pylori genome has been reported. It is assumed that the original Asian settlers of the Americas, thousands of years ago, brought with them HpAsian strains, of recognized low virulence. But today’s Amerindians harbor HpEurope, more virulent strains containing PAIs and associated with higher gastric cancer risk [3]. It would appear that the rise in gastric cancer rates observed for cohorts born after the mid-eighteenth century may be linked to environmental as well as secular trends in the evolution of the H. pylori genome. …